{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:14:56Z","timestamp":1791976496538,"version":"4.4.0"},"reference-count":84,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T00:00:00Z","timestamp":1752451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>This review summarizes the available evidence on hyaluronic acid\u2019s (HA\u2019s) role in immune response. HA is one of many components in the extracellular matrix that transmits signals from the extracellular microenvironment to cellular effector systems in immune cells. The final effect of these interactions depends on the type of cells and receptors used and the size of HA particles. HA\u2019s activation of intracellular signaling pathways leads to an immune response involving the release of pro- or anti-inflammatory cytokines and chemokines. These play a crucial role in defense mechanisms, such as protecting against pathogens and tissue healing after injuries. HA, as a signaling particle, is also involved in the intensification of the cytokine storm during COVID-19. Multifold increases in HA content in the lungs and the strength of its impact on the immune system define an \u201cHA storm\u201d. The molecular mechanisms involved in inflammation and initiation, including the promotion of cancer, also begin in the microenvironment, and hyaluronic acid is a key element. In this paper, we focus on intra- and intercellular signaling pathways using HA participation rather than injection preparation based on HA use for esthetic treatment.<\/jats:p>","DOI":"10.3390\/biom15071008","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T08:04:41Z","timestamp":1752566681000},"page":"1008","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Hyaluronic Acid in Immune Response"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6701-1861","authenticated-orcid":false,"given":"Lech","family":"Chrostek","sequence":"first","affiliation":[{"name":"Department of Biochemical Diagnostics, Medical University of Bialystok, 15-274 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogdan","family":"Cylwik","sequence":"additional","affiliation":[{"name":"Department of Paediatric Laboratory Diagnostics, Medical University of Bialystok, 15-269 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kobayashi, T., Chanmee, T., and Itano, N. (2020). Hyaluronan: Metabolism and Function. Biomolecules, 10.","DOI":"10.3390\/biom10111525"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lee, B.M., Park, S.J., Noh, I., and Kim, C.-H. (2021). The effects of the molecular weights of hyaluronic acid on the immune responses. Biomater. Res., 25.","DOI":"10.1186\/s40824-021-00228-4"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Donelan, W., Dominguez-Gutierrez, P.R., and Kusmartsev, S. (2022). Deregulated hyaluronan metabolism in the tumor microenvironment drives cancer inflammation and tumor associated immune suppression. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.971278"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.carres.2005.01.022","article-title":"Experimental approaches to hyaluronan structure","volume":"340","author":"Cowman","year":"2005","journal-title":"Carbohydr. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s00281-024-01024-7","article-title":"Role of Hyaluronic acid and its chemical derivatives in immunity during homeostasis, cancer and tissue regeneration","volume":"46","author":"Rosales","year":"2024","journal-title":"Semin. Immunopathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1046\/j.1365-2796.1997.00170.x","article-title":"Hyaluronan: Its nature, distribution, func- tions and turnover","volume":"242","author":"Fraser","year":"1997","journal-title":"J. Intern. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1021\/acsbiomaterials.5b00181","article-title":"High and low molecular weight hyaluronic acid differentially influence macrophage activation","volume":"1","author":"Rayahin","year":"2015","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1007\/s00011-004-1295-8","article-title":"CD44 and hyaluronic acid regulate in vivo iNOS expression and metalloproteinase activity in murine air-pouch inflammation","volume":"53","author":"Cabrera","year":"2004","journal-title":"Inflamm. Res."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"McDonald, B., and Kubes, P. (2015). Interactions between CD44 and hyaluronan in leukocyte trafficking. Front. Immunol., 6.","DOI":"10.3389\/fimmu.2015.00068"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1006\/scdb.2000.0244","article-title":"Hyaluronan in morphogenesis","volume":"12","author":"Toole","year":"2001","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Johnson, P., Arif, A.A., Lee-Sayer, S.S.M., and Dong, Y. (2018). Hyaluronan and Its Interactions with mmune Cells in the Healthy and Inflamed Lung. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02787"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1016\/0092-8674(90)90694-A","article-title":"CD44 is the principal cell surface receptor for hyaluronate","volume":"61","author":"Aruffo","year":"1990","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1002\/jcb.24054","article-title":"The inhibition of hyaluronan degradation reduced pro-inflammatory cytokines in mouse synovial fibroblasts subjected to collagen-induced arthritis","volume":"113","author":"Campo","year":"2012","journal-title":"Cell Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"25085","DOI":"10.1074\/jbc.274.35.25085","article-title":"Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties","volume":"274","author":"Itano","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/S0945-053X(01)00172-X","article-title":"The six hyaluronidase-like genes in the human and mouse genomes","volume":"20","author":"Csoka","year":"2001","journal-title":"Matrix Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1039\/c0ib00096e","article-title":"Hyaluronan metabolism in remodeling extracellular matrix: Probes for imaging and therapy of breast cancer","volume":"3","author":"Veiseh","year":"2011","journal-title":"Integr. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S0925-4439(97)00083-5","article-title":"Degradation of glycosaminoglycans by reactive oxygen species derived from stimulated polymorphonuclear leukocytes","volume":"1362","author":"Moseley","year":"1997","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Niemietz, I., and Brown, K.L. (2023). Hyaluronan promotes intracellular ROS production and apoptosis in TNF\u03b1-stimulated neutrophils. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1032469"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0144-8617(98)00084-8","article-title":"Identification of radicals from hyaluronan (hyaluronic acid) and cross-linked derivatives using electron paramagnetic resonance spectroscopy","volume":"38","author":"Hawkins","year":"1999","journal-title":"Carbohydr. Polym."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Lee-Sayer, S.S.M., Dong, Y., Arif, A.A., Olsson, M., Brown, K.L., and Johnson, P. (2015). The where, when, how, and why of hyaluronan binding by immune cells. Front. Immunol., 6.","DOI":"10.3389\/fimmu.2015.00150"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1038\/s41366-022-01187-z","article-title":"Small fragments of hyaluronan are increased in individuals with obesity and contribute to low-grade inflammation through TLR-mediated activation of innate immune cells","volume":"46","author":"Romo","year":"2022","journal-title":"Int. J. Obesity"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8191","DOI":"10.4049\/jimmunol.179.12.8191","article-title":"Hyaluronan Synthesis Is Required for IL-2-Mediated T Cell Proliferation","volume":"179","author":"Mahaffey","year":"2007","journal-title":"J. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"G309","DOI":"10.1152\/ajpgi.00248.2011","article-title":"Hyaluronic Acid Is Radioprotective in the iintestine through a TLR4 and COX-2-Mediated Mechanism","volume":"302","author":"Riehl","year":"2012","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Johnson, L.A., and Jackson, D.G. (2021). Hyaluronan and its receptors: Key mediators of immune cell entry and trafficking in the lymphatic system. Cells, 10.","DOI":"10.3390\/cells10082061"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Hoarau, A., Polette, M., and Coraux, C. (2022). Lung Hyaluronasome: Involvement of Low Molecular Weight Ha (Lmw-Ha) in Innate Immunity. Biomolecules, 12.","DOI":"10.3390\/biom12050658"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Dodd, R.J., Blundell, C.D., Sattelle, B.M., Enghild, J.J., Milner, C.M., and Day, A.J. (2024). Chemical modification of hyaluronan oligosaccharides differentially modulates hyaluronan\u2013hyaladherin interactions. J. Biol. Chem., 300.","DOI":"10.1101\/2024.03.12.584658"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1093\/glycob\/cwn109","article-title":"Hyaluronan receptors involved in cytokine induction in monocytes","volume":"19","author":"Yamawaki","year":"2009","journal-title":"Glycobiology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"17079","DOI":"10.1074\/jbc.M310859200","article-title":"Hyaluronan Fragments Stimulate Endothelial Recognition of Injury through TLR4","volume":"279","author":"Taylor","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6184","DOI":"10.4049\/jimmunol.159.12.6184","article-title":"Cytokine induction of the ability of human monocyte CD44 to bind hyaluronan is mediated primarily by TNF-alpha and is inhibited by IL-4 and IL-13","volume":"159","author":"Levesque","year":"1997","journal-title":"J. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Misra, S., Hascall, V.C., Markwald, R.R., and Ghatak, S. (2015). Interactions between Hyaluronian and its Rerceptors (CD44, RHAMM) Regulate the Activities of Inflammation and Cancer. Front. Immunol., 6.","DOI":"10.3389\/fimmu.2015.00201"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Weigel, P.H. (2020). Systemic glycosaminoglycan clearance by HARE\/Stabilin-2 activates Intracellular Signaling. Cells, 29.","DOI":"10.3390\/cells9112366"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.12998\/wjcc.v9.i7.1513","article-title":"Regulation of the expression of proinflammatory cytokines induced by SARS-CoV-2","volume":"9","author":"Zhang","year":"2021","journal-title":"World J. Clin. Cases"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4589","DOI":"10.1074\/jbc.R100038200","article-title":"Signaling Properties of Hyaluronan Receptors","volume":"277","author":"Turley","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.matbio.2018.02.001","article-title":"Hyaluronan in the lymphatics: The key role of the hyaluronan receptor LYVE-1 in leucocyte trafficking","volume":"78\u201379","author":"Jackson","year":"2019","journal-title":"Matrix Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"8014","DOI":"10.1074\/jbc.M115.708305","article-title":"Binding of Hyaluronan to the Native Lymphatic Vessel Endothelial Receptor LYVE-1 Is Critically Dependent on Receptor Clustering and Hyaluronan Organization","volume":"291","author":"Lawrance","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e202000908","DOI":"10.26508\/lsa.202000908","article-title":"Dendritic cell entry to lymphatic capillaries is orchestrated by CD44 and the hyaluronan glycocalyx","volume":"4","author":"Johnson","year":"2021","journal-title":"Life Sci. Alliance"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1091\/mbc.12.4.891","article-title":"Layilin, a novel integraal membran\u0119 protein, is a hyaluronian receptor","volume":"12","author":"Bono","year":"2017","journal-title":"Mol. Biol. Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.abb.2019.01.015","article-title":"Hyaluronan fragments produced during tissue injury: A signal amplifying the inflammatory response","volume":"663","author":"Avenoso","year":"2019","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e2202118","DOI":"10.1002\/adhm.202202118","article-title":"Hyaluronan Receptors as Mediators and Modulators of the Tumor Microenvironment","volume":"12","author":"Carvalho","year":"2023","journal-title":"Adv. Healthc. Mater."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s13770-019-00194-y","article-title":"Propofol suppresses LPS-induced inflammation in amnion cells via inhibition of NF-\u03baB activation","volume":"16","author":"Yoon","year":"2019","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.it.2005.09.009","article-title":"Hyaluronan cross-linking: A protective mechanism in inflammation?","volume":"26","author":"Day","year":"2005","journal-title":"Trends Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.2174\/138955709790361485","article-title":"Altered Hyaluronan Biosynthesis and Cancer Progression: An immunological perspective","volume":"9","author":"Alaniz","year":"2010","journal-title":"Mini-Rev. Med. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1074\/jbc.M113.510339","article-title":"Hyaluronic acid receptor for endocytosis (HARE)-mediated endocytosis of hyaluronan, heparin, dermatan sulfate, and acetylated low density lipoprotein (AcLDL), but not chondroitin sulfate types A, C, D, or E, activates NF-\u03baB-regulated gene expression","volume":"289","author":"Pandey","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.matbio.2023.02.005","article-title":"Targeting LAYN inhibits colorectal cancer metastasis and tumor-associated macrophage infiltration induced by hyaluronan oligosaccharides","volume":"117","author":"Yang","year":"2023","journal-title":"Matrix Biol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Berdiaki, A., Neagu, M., Spyridaki, I., Kuskov, A., Perez, S., and Nikitovic, D. (2023). Hyaluronan and reactive oxygen Species Signaling\u2014Novel cues from the Matrix?. Antioxidants, 12.","DOI":"10.3390\/antiox12040824"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1111\/j.1600-0625.2007.00638.x","article-title":"Hyaluronan fragments induce cytokine and metalloprotease upregulation in human melanoma cells in part by signalling via TLR4","volume":"17","author":"Voelcker","year":"2008","journal-title":"Exp. Dermatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1084\/jem.20001858","article-title":"Oligosaccharides of hyaluronan activate dendritic cells via toll-like receptor 4","volume":"195","author":"Termeer","year":"2002","journal-title":"J. Exp. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.4049\/jimmunol.159.5.2492","article-title":"Induction of IL-12 and chemokines by hyaluronan requires adhesion-dependent priming of resident but not elicited macrophages","volume":"159","author":"Noble","year":"1997","journal-title":"J. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1172\/JCI119054","article-title":"Hyaluronan (HA) fragments induce chemokine gene expression in alveolar macrophages. The role of HA size and CD44","volume":"98","author":"McKee","year":"1996","journal-title":"J. Clin. Investig."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3023","DOI":"10.4049\/jimmunol.160.6.3023","article-title":"Regulation of hyaluronan-induced chemokine gene expression by IL-10 and IFN-gamma in mouse macrophages","volume":"160","author":"Horton","year":"1998","journal-title":"J. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Jarczak, D., and Nierhaus, A. (2022). Cytokine Storm-Definition, Causes, and Implications. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911740"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"8198963","DOI":"10.1155\/2020\/8198963","article-title":"Cytokine Storm in COVID-19 Patients, Its Impact on Organs and Potential Treatment by QTY Code-Designed Detergent-Free Chemokine Receptors","volume":"2020","author":"Mustafa","year":"2020","journal-title":"Mediat. Inflamm."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Wu, D., and Yang, X.O. (2021). Dysregulation of Pulmonary Responses in Severe COVID-19. Viruses, 13.","DOI":"10.3390\/v13060957"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Hellman, U., Rosendal, E., Lehrstrand, J., Henriksson, J., Bj\u00f6rsell, T., Wennemo, A., Hahn, M., \u00d6sterberg, B., Dorofte, L., and Nilsson, E. (2024). SARS-CoV-2 infection induces hyaluronan production in vitro and hyaluronan levels in COVID-19 patients relate to morbidity and long-term lung impairment: A prospective cohort study. mBio, 15.","DOI":"10.1128\/mbio.01303-24"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1164\/rccm.200405-652OC","article-title":"Theroleofhyaluronan synthase 3inventilator-inducedlunginjury","volume":"172","author":"Bai","year":"2005","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.matbio.2023.02.001","article-title":"Hyaluronan in the pathogenesis of acute and post-acute COVID-19 infection","volume":"116","author":"Barnes","year":"2023","journal-title":"Matrix Biol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Dodd, R.J., Allen, J.E., and Day, A.J. (2024). Hyaluronan in COVID-19: A matrix for understanding lung disease. mBio, 15.","DOI":"10.1128\/mbio.02609-24"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.arcmed.2020.06.011","article-title":"Molecular Alterations Prompted by SARS-CoV-2 Infection: Induction of Hyaluronan, Glycosaminoglycan and Mucopolysaccharide Metabolism","volume":"51","author":"Torres","year":"2020","journal-title":"Arch. Med. Res."},{"key":"ref_59","first-page":"117","article-title":"Unraveled roles of hyaluronan in severe COVID-19","volume":"20","author":"Ontong","year":"2021","journal-title":"EXCLI J."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Cylwik, B., Gan, K., Kazberuk, M., Gruszewska, E., Panasiuk, A., and Chrostek, L. (2024). Diagnostic Usefulness of Serum Hyaluronic Acid in Patients with SARS-CoV-2 Infection. J. Clin. Med., 13.","DOI":"10.3390\/jcm13237471"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1002\/jlb.59.1.24","article-title":"Expression and regulation of chemokines in bacterial pneumonia","volume":"59","author":"Standiford","year":"1996","journal-title":"J. Leukoc. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.4049\/jimmunol.0903274","article-title":"Kinetics of chemokine-glycosaminoglycan interactions control neutrophil migration into the airspaces of the lungs","volume":"184","author":"Tanino","year":"2010","journal-title":"J. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5387\/fms.2023-07","article-title":"Roles of extracellular matrix in lung diseases","volume":"70","author":"Tanino","year":"2024","journal-title":"Fukushima J. Med. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.2353\/ajpath.2009.080831","article-title":"Platelet-derived hyaluronidase 2 cleaves hyaluronan into fragments that trigger monocyte-mediated production of proinflammatory cytokines","volume":"174","author":"Nigro","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1165\/rcmb.2007-0361OC","article-title":"Hyaluronidaseexpressio and activity is regulated by proinflammatory cytokines in human airway epithelial cells","volume":"39","author":"Monzon","year":"2008","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Petrey, A.C., and de laMotte, C.A. (2014). Hyaluronan, a crucial regulator of inflammation. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00101"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/0014-4827(90)90227-2","article-title":"TGF-b enhances the production of hyaluronan in human lung but not in skin fibroblasts","volume":"186","author":"Fransson","year":"1990","journal-title":"Exp. Cell Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.yjmcc.2024.11.009","article-title":"Hyaluronan provokes inflammation but suppresses phagocytotic function in macrophages","volume":"198","author":"Audam","year":"2025","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Dong, Y., Arif, A., Olsson, M., Cali, V., Hardman, B., Dosanjh, M., Lauer, M., Midura, R.J., Hascall, V.C., and Brown, K.L. (2016). Endotoxin free hyaluronan and hyaluronan fragments do not stimulate TNF-alpha, interleukin-12 or upregulate co-stimulatory molecules in dendritic cells or macrophages. Sci. Rep., 6.","DOI":"10.1038\/srep36928"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/mi.2017.83","article-title":"The survival of fetal and bone marrow monocyte-derived alveolar macrophages is promoted by CD44 and its interaction with hyaluronan","volume":"11","author":"Dong","year":"2018","journal-title":"Mucosal Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"41453","DOI":"10.1074\/jbc.M401678200","article-title":"Myofibroblastic differentiation leads to hyaluronan accumulation through reduced hyaluronan turnover","volume":"279","author":"Jenkins","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s10549-013-2804-7","article-title":"Hyaluronan synthases (HAS1-3) in stromal and malignant cells correlate with breast cancer grade and predict patient survival","volume":"143","author":"Auvinen","year":"2014","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_73","first-page":"5207","article-title":"Hyaluronan synthase 3 overexpression promotes the growth of TSU prostate cancer cells","volume":"61","author":"Liu","year":"2001","journal-title":"Cancer Res."},{"key":"ref_74","first-page":"1141","article-title":"Overproduction of hyaluronan by expression of the hyaluronan synthase Has2 enhances anchorage-independent growth and tumorigenicity","volume":"59","author":"Kosaki","year":"1999","journal-title":"Cancer Res."},{"key":"ref_75","first-page":"2638","article-title":"Evaluation of the prognostic potential of hyaluronic acid and hyaluronidase (HYAL1) for prostate cancer","volume":"63","author":"Posey","year":"2003","journal-title":"Cancer Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.yexcr.2005.07.026","article-title":"The over-expression of HAS2, hyal-2 and CD44 is implicated in the invasiveness of breast cancer","volume":"310","author":"Udabage","year":"2005","journal-title":"Exp. Cell Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.canlet.2016.02.031","article-title":"Hyaluronan: A modulator of the tumor microenvironment","volume":"375","author":"Chanmee","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1146\/annurev-genet-120417-031621","article-title":"The Hippo Signaling Network and Its Biological Functions","volume":"52","author":"Misra","year":"2018","journal-title":"Annu. Rev. Genet."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.devcel.2019.04.018","article-title":"High-molecular-weight hyaluronan is a hippo pathway ligand directing cel density-dependent growth inhibition via PAR1b","volume":"49","author":"Ooki","year":"2019","journal-title":"Dev. Cell"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.coph.2009.06.020","article-title":"Inflammation and cancer: How friendly is the relationship for cancer patients?","volume":"9","author":"Aggarwal","year":"2009","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.soc.2017.11.003","article-title":"Colon Cancer: Inflammation-Associated Cancer","volume":"27","author":"Shawki","year":"2018","journal-title":"Surg. Oncol. Clin. N. Am."},{"key":"ref_82","first-page":"1411","article-title":"Mechanisms by which inflammation may increase intestinal cancer risk in inflammatory bowel disease","volume":"6","author":"Lapointe","year":"2010","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/cmi.2009.43","article-title":"NF-\u03baB Signaling Pathway, Inflammation and Colorectal Cancer","volume":"6","author":"Wang","year":"2009","journal-title":"Cell Mol. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/nature02924","article-title":"NF-\u03baB functions as a tumour promoter in inflammation-associated cancer","volume":"431","author":"Pikarsky","year":"2004","journal-title":"Nature"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/7\/1008\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:09:39Z","timestamp":1760033379000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/7\/1008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,14]]},"references-count":84,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["biom15071008"],"URL":"https:\/\/doi.org\/10.3390\/biom15071008","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,14]]}}}