{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T19:07:36Z","timestamp":1788808056558,"version":"build-2803163510"},"reference-count":111,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T00:00:00Z","timestamp":1740960000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"KU Leuven","award":["14\/23\/143"],"award-info":[{"award-number":["14\/23\/143"]}]},{"name":"KU Leuven","award":["G036423N"],"award-info":[{"award-number":["G036423N"]}]},{"name":"FWO-Vlaanderen","award":["14\/23\/143"],"award-info":[{"award-number":["14\/23\/143"]}]},{"name":"FWO-Vlaanderen","award":["G036423N"],"award-info":[{"award-number":["G036423N"]}]},{"name":"Rega Foundation","award":["14\/23\/143"],"award-info":[{"award-number":["14\/23\/143"]}]},{"name":"Rega Foundation","award":["G036423N"],"award-info":[{"award-number":["G036423N"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The acute phase response is a hallmark of all inflammatory reactions and acute phase reactants, such as C-reactive protein (CRP) and serum amyloid A (SAA) proteins, are among the most useful plasma and serum markers of inflammation in clinical medicine. Although it is well established that inflammatory cytokines, mainly interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-\u03b1 (TNF-\u03b1) induce SAA in the liver, the biological functions of elicited SAA remain an enigma. By the classical multi-step protein purification studies of chemotactic factors present in plasma or serum, we discovered novel chemokines and SAA1 fragments, which are induced during inflammatory reactions. In contrast to earlier literature, pure SAA1 fails to induce chemokines, an ascribed function that most probably originates from contaminating lipopolysaccharide (LPS). However, intact SAA1 and fragments thereof synergize with CXC and CC chemokines to enhance chemotaxis. Natural SAA1 fragments are generated by inflammatory proteinases such as matrix metalloproteinase-9 (MMP-9). They mediate synergy with chemokines by the interaction with cognate G protein-coupled receptors (GPCRs), formyl peptide receptor 2 (FPR2) and (CC and CXC) chemokine receptors. In conclusion, SAA1 enforces the action of many chemokines and assists in local leukocyte recruitment, in particular, when the concentrations of specifically-induced chemokines are still low.<\/jats:p>","DOI":"10.3390\/ijms26052258","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T03:26:21Z","timestamp":1741058781000},"page":"2258","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Functional Interactions Between Recombinant Serum Amyloid A1 (SAA1) and Chemokines in Leukocyte Recruitment"],"prefix":"10.3390","volume":"26","author":[{"given":"Jo","family":"Van Damme","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Immunology, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4558-0769","authenticated-orcid":false,"given":"Sofie","family":"Struyf","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0133-5545","authenticated-orcid":false,"given":"Paul","family":"Proost","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1714-2294","authenticated-orcid":false,"given":"Ghislain","family":"Opdenakker","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mieke","family":"Gouwy","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/S0167-5699(99)01469-3","article-title":"The chemokine system: Redundancy for robust outputs","volume":"20","author":"Mantovani","year":"1999","journal-title":"Immunol. Today"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1056\/NEJM199902113400607","article-title":"Acute-phase proteins and other systemic responses to inflammation","volume":"340","author":"Gabay","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1631\/jzus.2005.B1045","article-title":"Acute phase reaction and acute phase proteins","volume":"6","author":"Gruys","year":"2005","journal-title":"J. Zhejiang Univ. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.2174\/0929867323666160418114600","article-title":"Structure and expression of different serum amyloid A (SAA) variants and their concentration-dependent functions during host insults","volume":"23","author":"Gouwy","year":"2016","journal-title":"Curr. Med. Chem."},{"key":"ref_5","first-page":"913","article-title":"Chemokine gene expression and secretion by cytokine-activated human microvascular endothelial cells. Differential regulation of monocyte chemoattractant protein-1 and interleukin-8 in response to interferon-gamma","volume":"145","author":"Brown","year":"1994","journal-title":"Am. J. Pathol."},{"key":"ref_6","first-page":"271","article-title":"Expression of monocyte chemotactic protein-3 in human monocytes and endothelial cells","volume":"8","author":"Polentarutti","year":"1997","journal-title":"Eur. Cytokine Netw."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.cytogfr.2005.03.005","article-title":"Synergy in cytokine and chemokine networks amplifies the inflammatory response","volume":"16","author":"Gouwy","year":"2005","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7251","DOI":"10.1073\/pnas.84.20.7251","article-title":"Interferon beta 2\/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells","volume":"84","author":"Gauldie","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1002\/eji.1830180817","article-title":"Interleukin 6, the third mediator of acute-phase reaction, modulates hepatic protein synthesis in human and mouse. Comparison with interleukin 1 beta and tumor necrosis factor-alpha","volume":"18","author":"Ramadori","year":"1988","journal-title":"Eur. J. Immunol."},{"key":"ref_10","first-page":"31","article-title":"Production of interleukin-8 by human dermal fibroblasts and keratinocytes in response to interleukin-1 or tumour necrosis factor","volume":"68","author":"Larsen","year":"1989","journal-title":"Immunology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/314266a0","article-title":"Homogeneous interferon-inducing 22K factor is related to endogenous pyrogen and interleukin-1","volume":"314","author":"Opdenakker","year":"1985","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1111\/j.1432-1033.1987.tb13452.x","article-title":"Purification and characterization of human fibroblast-derived hybridoma growth factor identical to T-cell-derived B-cell stimulatory factor-2 (interleukin-6)","volume":"168","author":"Cayphas","year":"1987","journal-title":"Eur. J. Biochem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"144","DOI":"10.4049\/jimmunol.142.1.144","article-title":"Bacterial lipopolysaccharide and inflammatory mediators augment IL-6 secretion by human endothelial cells","volume":"142","author":"Jirik","year":"1989","journal-title":"J. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"760","DOI":"10.4049\/jimmunol.148.3.760","article-title":"Expression of a monocyte chemotactic cytokine by human mononuclear phagocytes","volume":"148","author":"Colotta","year":"1992","journal-title":"J. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1002\/jlb.63.3.364","article-title":"Synergistic induction of MCP-1 and -2 by IL-1\u03b2 and interferons in fibroblasts and epithelial cells","volume":"63","author":"Struyf","year":"1998","journal-title":"J. Leukoc. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1097\/01.LAB.0000048719.53282.00","article-title":"The CXC chemokine GCP-2\/CXCL6 is predominantly induced in mesenchymal cells by interleukin-1\u03b2 and is down-regulated by interferon-\u03b3: Comparison with interleukin-8\/CXCL8","volume":"83","author":"Wuyts","year":"2003","journal-title":"Lab. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.yexcr.2004.09.027","article-title":"GCP-2\/CXCL6 synergizes with other endothelial cell-derived chemokines in neutrophil mobilization and is associated with angiogenesis in gastrointestinal tumors","volume":"303","author":"Gijsbers","year":"2005","journal-title":"Exp. Cell Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1038\/labinvest.3700453","article-title":"TLR ligands and cytokines induce CXCR3 ligands in endothelial cells: Enhanced CXCL9 in autoimmune arthritis","volume":"86","author":"Loos","year":"2006","journal-title":"Lab. Investig."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1056\/NEJM198411293112205","article-title":"Interleukin-1 and the pathogenesis of the acute-phase response","volume":"311","author":"Dinarello","year":"1984","journal-title":"N. Engl. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/1043-4666(91)90041-B","article-title":"Constitutive and NF-\u03baB-like proteins in the regulation of the serum amyloid A gene by interleukin-1","volume":"3","author":"Edbrooke","year":"1991","journal-title":"Cytokine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"25624","DOI":"10.1016\/S0021-9258(19)74435-4","article-title":"The role of NF-\u03baB and NF-IL-6 transactivating factors in the synergistic activation of human serum amyloid A gene expression by interleukin-1 and interleukin-6","volume":"268","author":"Betts","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"825","DOI":"10.4049\/jimmunol.154.2.825","article-title":"Induction of human serum amyloid A in Hep 3B cells by IL-6 and IL-1 beta involves both transcriptional and post-transcriptional mechanisms","volume":"154","author":"Jiang","year":"1995","journal-title":"J. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1089\/jir.1987.7.429","article-title":"Virus interference. I. The interferon. By A. Isaacs and J. Lindenmann, 1957","volume":"7","author":"Isaacs","year":"1987","journal-title":"J. Interferon Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1126\/science.168.3929.398","article-title":"Interferon","volume":"168","author":"Vilcek","year":"1970","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6134","DOI":"10.1073\/pnas.77.10.6134","article-title":"Purification and some characteristics of human T-cell growth factor from phytohemagglutinin-stimulated lymphocyte-conditioned media","volume":"77","author":"Mier","year":"1980","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3424","DOI":"10.1021\/bi00359a049","article-title":"Purification and biochemical characteristics of two distinct human interleukins 1 from the myelomonocytic THP-1 cell line","volume":"25","author":"Matsushima","year":"1986","journal-title":"Biochemistry"},{"key":"ref_27","first-page":"67","article-title":"The detection and initial characterization of colony-stimulating factors in synovial fluid","volume":"72","author":"Williamson","year":"1988","journal-title":"Clin. Exp. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1128\/iai.61.1.64-70.1993","article-title":"Purification of a factor which provides a costimulatory signal for gamma interferon production","volume":"61","author":"Nakamura","year":"1993","journal-title":"Infect. Immun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1182\/blood.V97.8.2197","article-title":"Identification of a blood-derived chemoattractant for neutrophils and lymphocytes as a novel CC chemokine, Regakine-1","volume":"97","author":"Struyf","year":"2001","journal-title":"Blood"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.bcp.2012.11.027","article-title":"Identification and characterization of MIP-1\u03b1\/CCL3 isoform 2 from bovine serum as a potent monocyte\/dendritic cells chemoattractant","volume":"85","author":"Gouwy","year":"2013","journal-title":"Biochem. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"106620","DOI":"10.1016\/j.pep.2024.106620","article-title":"Nature of recombinant human serum amyloid A1 in Escherichia coli and its preferable approach for purification","volume":"227","author":"Ahmad","year":"2025","journal-title":"Protein Expr. Purif."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/0022-1759(89)90199-3","article-title":"A method for removing interleukin-1 and tumor necrosis factor-inducing substances from bacterial cultures by ultrafiltration with polysulfone","volume":"116","author":"Schindler","year":"1989","journal-title":"J. Immunol. Methods"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.4049\/jimmunol.1800503","article-title":"Bacterial lipoproteins constitute the TLR2-stimulating activity of serum amyloid A","volume":"201","author":"Burgess","year":"2018","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"843","DOI":"10.3389\/fimmu.2020.00843","article-title":"Serum amyloid A1 (SAA1) revisited: Restricted leukocyte-activating properties of homogeneous SAA1","volume":"11","author":"Berghmans","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s11883-020-00888-y","article-title":"Structural Basis for Vital Function and Malfunction of Serum Amyloid A: An Acute-Phase Protein that Wears Hydrophobicity on Its Sleeve","volume":"22","author":"Gursky","year":"2020","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1182\/blood.V90.3.909","article-title":"Chemokines","volume":"90","author":"Rollins","year":"1997","journal-title":"Blood"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S1074-7613(00)80165-X","article-title":"Chemokines: A new classification system and their role in immunity","volume":"12","author":"Zlotnik","year":"2000","journal-title":"Immunity"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"292","DOI":"10.4049\/jimmunol.145.1.292","article-title":"Identification of high affinity receptors for human monocyte chemoattractant protein-1 on human monocytes","volume":"145","author":"Yoshimura","year":"1990","journal-title":"Eur. J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"24934","DOI":"10.1074\/jbc.272.40.24934","article-title":"The second extracellular loop of CCR5 is the major determinant of ligand specificity","volume":"272","author":"Samson","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4588","DOI":"10.1182\/blood.V90.11.4588","article-title":"The CXC-chemokine neutrophil-activating peptide-2 induces two distinct optima of neutrophil chemotaxis by differential interaction with interleukin-8 receptors CXCR-1 and CXCR-2","volume":"90","author":"Ludwig","year":"1997","journal-title":"Blood"},{"key":"ref_41","first-page":"73","article-title":"Isolation and identification of naturally modified C-C chemokines MCP-1, MCP-2 and RANTES: Effects of posttranslational modifications on receptor usage, chemotactic and anti-HIV-1 activity","volume":"9","author":"Proost","year":"1998","journal-title":"Eur. Cytokine Netw."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0031-6997(24)01439-X","article-title":"International Union of Pharmacology. XXII. Nomenclature for chemokine receptors","volume":"52","author":"Murphy","year":"2000","journal-title":"Pharmacol. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/84224","article-title":"Dancing to the tune of chemokines","volume":"2","author":"Thelen","year":"2001","journal-title":"Nat. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/S1471-4906(01)01941-X","article-title":"Decoy receptors: A strategy to regulate inflammatory cytokines and chemokines","volume":"22","author":"Mantovani","year":"2001","journal-title":"Trends Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1124\/pr.54.2.227","article-title":"International Union of Pharmacology. XXX. Update on Chemokine Receptor Nomenclature","volume":"54","author":"Murphy","year":"2002","journal-title":"Pharmacol. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1146\/annurev.immunol.22.012703.104543","article-title":"Chemokines in innate and adaptive host defense: Basic chemokinese grammar for immune cells","volume":"22","author":"Rot","year":"2004","journal-title":"Annu. Rev. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1073\/pnas.80.3.765","article-title":"Structural and biological characteristics of connective tissue activating peptide (CTAP-III), a major human platelet-derived growth factor","volume":"80","author":"Castor","year":"1983","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1084\/jem.171.4.1091","article-title":"Lipopolysaccharide-stimulated human monocytes secrete, apart from neutrophil-activating peptide 1\/interleukin 8, a second neutrophil-activating protein. NH2-terminal amino acid sequence identity with melanoma growth stimulatory activity","volume":"171","author":"Persoon","year":"1990","journal-title":"J. Exp. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"6338","DOI":"10.1074\/jbc.270.11.6338","article-title":"Limited and defined truncation at the C terminus enhances receptor binding and degranulation activity of the neutrophil-activating peptide 2 (NAP-2). Comparison of native and recombinant NAP-2 variants","volume":"270","author":"Ehlert","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1002\/jlb.59.1.67","article-title":"Human monocyte chemotactic proteins-2 and -3: Structural and functional comparison with MCP-1","volume":"59","author":"Proost","year":"1996","journal-title":"J. Leukoc. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"11715","DOI":"10.1021\/bi010224+","article-title":"Gene cloning of a new plasma CC chemokine, activating and attracting myeloid cells in synergy with other chemoattractants","volume":"40","author":"Struyf","year":"2001","journal-title":"Biochemistry"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.4049\/jimmunol.141.3.1018","article-title":"A human T-cell specific molecule is a member of a new gene family","volume":"141","author":"Schall","year":"1988","journal-title":"J. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1002\/(SICI)1521-4141(199902)29:02<633::AID-IMMU633>3.0.CO;2-I","article-title":"Selective expression of liver and activation-regulated chemokine (LARC) in intestinal epithelium in mice and humans","volume":"29","author":"Tanaka","year":"1999","journal-title":"Eur. J. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.imlet.2006.04.007","article-title":"\u201cDirty little secrets\u201d-endotoxin contamination of recombinant proteins","volume":"106","author":"Wakelin","year":"2006","journal-title":"Immunol. Lett."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Schwarz, H., Schmittner, M., Duschl, A., and Horejs-Hoeck, J. (2014). Residual endotoxin contaminations in recombinant proteins are sufficient to activate human CD1c+ dendritic cells. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0113840"},{"key":"ref_56","first-page":"6087109","article-title":"Biological characterization of commercial recombinantly expressed immunomodulating proteins contaminated with bacterial products in the year 2020: The SAA3 case","volume":"6","author":"Berghmans","year":"2020","journal-title":"Mediat. Inflamm."},{"key":"ref_57","unstructured":"Freshney, R.I. (1987). Culture of Animal Cells. A Manual of Basic Technique, Alan R Liss Inc."},{"key":"ref_58","unstructured":"Davis, J.M. (1998). Culture media. Basic Cell Culture. A Practical Approach, Oxford University Press."},{"key":"ref_59","unstructured":"Helgason, C.D. (2005). Culture of primary adherent cells and a continuously growing nonadherent cell line. Basic Cell Culture Protocols, Humana Press."},{"key":"ref_60","first-page":"439","article-title":"COOH-terminal SAA1 peptides fail to induce chemokines but synergize with CXCL8 and CCL3 to recruit leukocytes via FPR2","volume":"131","author":"Gouwy","year":"2018","journal-title":"Blood"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5940","DOI":"10.1158\/0008-5472.CAN-06-4682","article-title":"Platelet factor-4 variant chemokine CXCL4L1 inhibits melanoma and lung carcinoma growh and matastasis by preventing angiogenesis","volume":"67","author":"Struyf","year":"2007","journal-title":"Cancer Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cytogfr.2010.10.011","article-title":"The role of the CXC chemokines platelet factor-4 (CXCL4\/PF-4) and its variant (CXCL4L1\/PF-4var) in inflammation, angiogenesis and cancer","volume":"22","author":"Vandercappellen","year":"2001","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/jlb.60.1.147","article-title":"Cloning and functional expression of CC CKR5, a human monocyte CC chemokine receptor selective for MIP-1 (alpha), MIP-1 (beta), and RANTES","volume":"60","author":"Ahuja","year":"1996","journal-title":"J. Leukoc. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"19972","DOI":"10.1074\/jbc.273.32.19972","article-title":"The N-terminal extracellular segments of the chemokine receptors CCR1 and CCR3 are determinants for MIP-1alpha and eotaxin binding, respectively, but a second domain is essential for efficient receptor activation","volume":"273","author":"Pease","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.imbio.2013.10.004","article-title":"Chemokines and other GPCR ligands synergize in receptor-mediated migration of monocyte-derived immature and mature dendritic cells","volume":"219","author":"Gouwy","year":"2014","journal-title":"Immunobiology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1124\/mol.62.1.173","article-title":"The unique property of the CC chemokine regakine-1 to synergize with other plasma-derived inflammatory mediators in neutrophil chemotaxis does not reside in its NH2-terminal structure","volume":"62","author":"Gouwy","year":"2002","journal-title":"Mol. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1084\/jem.189.2.395","article-title":"A seven-transmembrane, G protein-coupled receptor, FPRL1, mediates the chemotactic activity of serum amyloid A for human phagocytic cells","volume":"189","author":"Su","year":"1999","journal-title":"J. Exp. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1002\/eji.201444818","article-title":"Serum amyloid A chemoattracts immature dendritic cells and indirectly provokes monocyte chemotaxis by induction of cooperating CC and CXC chemokines","volume":"45","author":"Gouwy","year":"2015","journal-title":"Eur. J. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.3389\/fimmu.2018.01081","article-title":"Matrix metalloproteinase-9-generated COOH-, but not NH2-terminal fragments of serum amyloid A1 retain potentiating activity in neutrophil migration to CXCL8, with loss of direct chemotactic and cytokine-inducing capacity","volume":"9","author":"Gouwy","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1084\/jem.167.6.1939","article-title":"Cloning and characterization of a cDNA for murine macrophage inflammatory protein (MIP), a novel monokine with inflammatory and chemokinetic properties","volume":"167","author":"Davatelis","year":"1988","journal-title":"J. Exp. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0065-2776(08)60509-X","article-title":"Interleukin-8 and related chemotactic cytokines- CXC and CC chemokines","volume":"55","author":"Baggiolini","year":"1994","journal-title":"Adv. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1124\/mol.108.045146","article-title":"Synergy between coproduced CC and CXC chemokines in monocyte chemotaxis through receptor-mediated events","volume":"74","author":"Gouwy","year":"2008","journal-title":"Mol. Pharmacol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1002\/eji.200838906","article-title":"Synergy-inducing chemokines enhance CCR2 ligand activities on monocytes","volume":"39","author":"Kuscher","year":"2009","journal-title":"Eur. J. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1182\/blood-2002-05-1431","article-title":"Serum amyloid A induces IL-8 secretion through a G protein-coupled receptor, FPRL1\/LXA4R","volume":"101","author":"He","year":"2003","journal-title":"Blood"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.atherosclerosis.2009.05.007","article-title":"Serum amyloid A induction of cytokines in monocytes\/macrophages and lymphocytes","volume":"207","author":"Song","year":"2009","journal-title":"Atherosclerosis"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"302","DOI":"10.3858\/emm.2010.42.4.029","article-title":"A pertussis toxin sensitive G-protein-independent pathway is involved in serum amyloid A-induced formyl peptide receptor 2-mediated CCL2 production","volume":"42","author":"Lee","year":"2010","journal-title":"Exp. Mol. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1189\/jlb.3A0315-085R","article-title":"Serum amyloid A1\u03b1 induces paracrine IL-8\/CXCL8 via TLR2 and directly synergizes with this chemokine via CXCR2 and formyl peptide receptor 2 to recruit neutrophils","volume":"98","author":"Berghmans","year":"2015","journal-title":"J. Leukoc. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1164\/rccm.200905-0696OC","article-title":"Serum amyloid A regulates granulomatous inflammation in sarcoidosis through Toll-like receptor-2","volume":"181","author":"Chen","year":"2010","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3887","DOI":"10.1038\/onc.2011.112","article-title":"Pleiotropic regulation of macrophage polarization and tumorigenesis by formyl peptide receptor-2","volume":"30","author":"Li","year":"2011","journal-title":"Oncogene"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.mvr.2013.07.011","article-title":"Serum amyloid A activation of human coronary artery endothelial cells exhibits a neutrophil promoting molecular profile","volume":"90","author":"Lakota","year":"2013","journal-title":"Microvasc. Res."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"De Seny, D., Cobraiville, G., Charlier, E., Neuville, S., Esser, N., Malaise, D., Mailaise, O., Calvo, F.Q., Relic, B., and Malaise, M.G. (2013). Acute-phase serum amyloid A in osteoarthritis: Regulatory mechanism and proinflammatory properties. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066769"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1111\/imm.12260","article-title":"Serum amyloid A induces interleukin-6 in dermal fibroblasts via Toll-like receptor 2, interleukin-1 receptor-associated kinase 4 and nuclear factor-\u0138B","volume":"143","author":"Cant","year":"2014","journal-title":"Immunology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1111\/cei.12458","article-title":"Serum amyloid A induces interleukin-1beta secretion from keratinocytes via the NACHT, LRR and PYD domains-containing protein 3 inflammasome","volume":"179","author":"Yu","year":"2015","journal-title":"Clin. Exp. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1038\/76216","article-title":"Receptor-dependent cell stress and amyloid accumulation in systemic amyloidosis","volume":"6","author":"Yan","year":"2000","journal-title":"Nat. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2954","DOI":"10.1074\/jbc.M411555200","article-title":"Serum amyloid A is a ligand for scanvenger receptor class B type I and inhibits high density lipoprotein binding and selective lipid uptake","volume":"280","author":"Cai","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"22","DOI":"10.4049\/jimmunol.181.1.22","article-title":"Cutting edge: TLR2 is a functional receptor for acute-phase serum amyloid A","volume":"181","author":"Cheng","year":"2008","journal-title":"J. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.2353\/ajpath.2010.090014","article-title":"A role for the high-density lipoprotein receptor SR-B1 in synovial inflammation via serum amyloid A","volume":"176","author":"Mullan","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"515","DOI":"10.2119\/molmed.2015.00109","article-title":"Serum amyloid A stimulates PKR expression and HMGB1 release possibly through TLR4\/RAGE receptors","volume":"21","author":"Li","year":"2015","journal-title":"Mol. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.scr.2015.06.008","article-title":"Acute phase serum amyloid A induces proinflammatory cytokines and mineralization via toll-like receptor 4 in mesenchymal stem cells","volume":"15","author":"Ebert","year":"2015","journal-title":"Stem Cell Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1136\/annrheumdis-2015-207655","article-title":"Acute serum amyloid A is an endogenous TLR2 ligand that mediates inflammatory and angiogenic mechanisms","volume":"75","author":"Connolly","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1111\/exd.12979","article-title":"Serum amyloid A1 secreted from UV-irradiated keratinocytes induces matrix metalloproteinase-1 in fibroblasts through toll-like receptor 4","volume":"25","author":"Han","year":"2016","journal-title":"Exp. Dermatol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Baranova, I.N., Souza, A.C.P., Bocharov, A.V., Vishnyakova, T.G., Hu, X., Vaisman, B.L., Amar, M.J., Chen, Z., Remaley, A.T., and Patterson, A.P. (2017). Human SR-BII mediates SAA uptake and contributes to SAA pro-inflammatory signaling in vitro and in vivo. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0175824"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/imm.13295","article-title":"The turning away of serum amyloid A biological activities and receptor usage","volume":"163","author":"Gouwy","year":"2021","journal-title":"Immunology"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2801","DOI":"10.4049\/jimmunol.166.4.2801","article-title":"Serum amyloid A (apoSAA) expression is up-regulated in rheumatoid arthritis and induces transcription of matrix metalloproteinases","volume":"166","author":"Vallon","year":"2001","journal-title":"J. Immunol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.bbrc.2005.03.069","article-title":"Serum amyloid A stimulates matrix-metalloproteinase-9 upregulation via formyl peptide receptor like-1-mediated signaling in human monocytic cells","volume":"330","author":"Lee","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1002\/art.33455","article-title":"Acute-phase serum amyloid A regulates tumor necrosis factor alpha and matrix turnover and predicts disease progression in patients with inflammatory arthritis before and after biologic therapy","volume":"64","author":"Connolly","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.imlet.2018.06.001","article-title":"The ectoenzyme-side of matrix metalloproteinases (MMPs) makes inflammation by serum amyloid A (SAA) and chemokines go round","volume":"205","author":"Gouwy","year":"2019","journal-title":"Immunol. Lett."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"5495","DOI":"10.4049\/jimmunol.152.11.5495","article-title":"Induction of monocyte chemotactic proteins MCP-1 and MCP-2 in human fibroblasts and leukocytes by cytokines and cytokine inducers. Chemical synthesis of MCP-2 and development of specific RIA","volume":"152","author":"Proost","year":"1994","journal-title":"J. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0006-291X(88)80043-3","article-title":"Role of interleukin-6 in regulating synthesis of C-reactive protein and serum amyloid A in human hepatoma cell lines","volume":"157","author":"Ganapathi","year":"1988","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.4049\/jimmunol.147.4.1261","article-title":"Effect of combinations of cytokines and hormones on synthesis of serum amyloid A and C-reactive protein in Hep 3B cells","volume":"147","author":"Ganapathi","year":"1991","journal-title":"J. Immunol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.imlet.2012.04.005","article-title":"Possible mechanisms involved in chemokine synergy fine tuning the inflammatory response","volume":"145","author":"Gouwy","year":"2012","journal-title":"Immunol. Lett."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1189\/jlb.1008638","article-title":"CC chemokine ligand-2 synergizes with the nonchemokine G protein-coupled receptor ligand fMLP in monocyte chemotaxis, and it cooperates with the TLR ligand LPS via induction of CXCL8","volume":"86","author":"Gouwy","year":"2009","journal-title":"J. Leukoc. Biol."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"den Hartigh, L.J., May, K.S., Zhang, X.S., Chait, A., and Blaser, M.J. (2023). Serum amyloid A and metabolic disease: Evidence for a critical role in chronic inflammatory conditions. Front. Cardiovasc. Med., 10.","DOI":"10.3389\/fcvm.2023.1197432"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e167835","DOI":"10.1172\/JCI167835","article-title":"Serum amyloid A expression in liver promotes synovial macrophage activation and chronic arthritis via NFAT5","volume":"134","author":"Li","year":"2024","journal-title":"J. Clin. Investig."},{"key":"ref_105","first-page":"3249","article-title":"New regulatory roles for human serum amyloid A","volume":"3","year":"2024","journal-title":"Int. J. Res. Oncol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/s41420-023-01455-5","article-title":"Serum amyloid protein A in inflammatory bowel disease: From bench to bedside","volume":"9","author":"Chen","year":"2023","journal-title":"Cell Death Discov."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1111\/j.1365-3083.1995.tb03538.x","article-title":"Cathepsin B generates the most common form of amyloid A (76 residues) as a degradation product from serum amyloid A","volume":"41","author":"Yamada","year":"1995","journal-title":"Scan. J. Immunol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/S0002-9440(10)61727-0","article-title":"Proteolysis of AA amyloid fibril proteins by matrix metalloproteinases-1, -2, and -3","volume":"159","author":"Stix","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1136\/ard.2004.030429","article-title":"Proteolysis of serum amyloid A and AA amyloid proteins by cysteine proteases: Cathepsin B generates AA amyloid proteins and cathepsin L may prevent their formation","volume":"64","author":"Menard","year":"2005","journal-title":"Ann. Rheum. Dis."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1093\/rheumatology\/ken371","article-title":"Increased susceptibility of serum amyloid A 1.1 to degradation by MMP-1: Potential explanation for higher risk of type AA amyloidosis","volume":"47","author":"Yamada","year":"2008","journal-title":"Rheumatology"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.cytogfr.2019.10.006","article-title":"Cytokines and serum amyloid A in the pathogenesis of hepatitis C virus infection","volume":"50","author":"Lavie","year":"2019","journal-title":"Cytokine Growth Factor Rev."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/5\/2258\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:46:32Z","timestamp":1760028392000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/5\/2258"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,3]]},"references-count":111,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["ijms26052258"],"URL":"https:\/\/doi.org\/10.3390\/ijms26052258","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,3]]}}}