{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T11:18:22Z","timestamp":1772882302237,"version":"3.50.1"},"reference-count":67,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,21]],"date-time":"2021-08-21T00:00:00Z","timestamp":1629504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No.32002200"],"award-info":[{"award-number":["No.32002200"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20190898"],"award-info":[{"award-number":["BK20190898"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>In subacute rumen acidosis (SARA), the rumen epithelium is frequently attacked by endotoxin (LPS), which is caused by the lysis of dead Gram-negative bacteria. However, the rumen epithelium innate immune system can actively respond to the infection. Previous studies have demonstrated that tea tree oil (TTO) has good bactericidal and anti-inflammatory effects. Therefore, the aim of this study was to investigate the effect of TTO on the expression of genes involved in the inflammatory cytokines in goat rumen epithelial cells (GRECs) triggered by LPS. Our study shows that rumen epithelial cells isolated from goat rumen tissue can be cultured in vitro in 0.25% trypsin for a long time. These cells were identified as epithelial cells by the expression of cytokeratin 18, monocarboxylate transporter 4 (MCT4), Na[+]\/H[+] hydrogen exchanger 1 (NHE1), putative anion transporter 1 (PAT1), vH+ ATPase B subunit (vH+ ATPase), and anion exchanger 2 (AE2). The mRNA expression of IL-1\u03b2, IL-6, TNF-\u03b1, TLR-2, NF-\u03baB, CXCL6 and CXCL8 genes was significantly increased when LPS was used compared to untreated controls. In addition, mRNA expression of IL-1\u03b2, IL-6, TNF-\u03b1, TLR-2, NF-\u03baB, CXCL8, CXCL6 and interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) genes was also significantly higher in the LPS group compared to the 0.05% TTO group. However, the expression of IL-1\u03b2, IL-6, TNF-\u03b1, TLR-2, CXCL6 and IFIT3 genes was significantly lower in the LPS and 0.05% TTO group compared to the 1 \u03bcg\/mL LPS group. These results suggest that TTO can inhibit LPS-induced inflammatory cytokines expression in GRECs.<\/jats:p>","DOI":"10.3390\/ani11082460","type":"journal-article","created":{"date-parts":[[2021,8,22]],"date-time":"2021-08-22T21:42:12Z","timestamp":1629668532000},"page":"2460","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Effect of Tea Tree Oil on the Expression of Genes Involved in the Innate Immune System in Goat Rumen Epithelial Cells"],"prefix":"10.3390","volume":"11","author":[{"given":"Zixuan","family":"Hu","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao","family":"Lin","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyu","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoqi","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kang","family":"Zhan","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.tvjl.2007.12.021","article-title":"The monitoring, prevention and treatment of sub-acute ruminal acidosis (SARA): A review","volume":"176","author":"Enemark","year":"2008","journal-title":"Vet. J."},{"key":"ref_2","unstructured":"Mutsvangwa, T., and Wright, T. (2003). Sub-Acute Ruminal Acidosis (SARA) in Dairy Cows."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.3168\/jds.S0022-0302(05)72807-1","article-title":"Subacute Ruminal Acidosis Induces Ruminal Lipopolysaccharide Endotoxin Release and Triggers an Inflammatory Response","volume":"88","author":"Gozho","year":"2005","journal-title":"J. Dairy Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.2527\/jas.2010-3301","article-title":"Ruminant Nutrition Symposium: Role of fermentation acid absorption in the regulation of ruminal pH12","volume":"89","author":"Aschenbach","year":"2011","journal-title":"J. Anim. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/j.rvsc.2012.02.004","article-title":"Interplay between rumen digestive disorders and diet-induced inflammation in dairy cattle","volume":"93","author":"Zebeli","year":"2012","journal-title":"Res. Vet. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1017\/S1751731114001128","article-title":"High concentrate-induced subacute ruminal acidosis (SARA) increases plasma acute phase proteins (APPs) and cortisol in goats","volume":"8","author":"Jia","year":"2014","journal-title":"Animal"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"856","DOI":"10.3168\/jds.S0022-0302(07)71569-2","article-title":"Ruminal Lipopolysaccharide Concentration and Inflammatory Response During Grain-Induced Subacute Ruminal Acidosis in Dairy Cows","volume":"90","author":"Gozho","year":"2007","journal-title":"J. Dairy Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40104-016-0100-1","article-title":"High-concentrate feeding upregulates the expression of inflammation-related genes in the ruminal epithelium of dairy cattle","volume":"7","author":"Zhang","year":"2016","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1080\/19336896.2016.1254857","article-title":"Role of polysaccharide and lipid in lipopolysaccharide induced prion protein conversion","volume":"10","author":"LeVatte","year":"2016","journal-title":"Prion"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"10689","DOI":"10.1074\/jbc.274.16.10689","article-title":"Toll-like Receptor-4 Mediates Lipopolysaccharide-induced Signal Transduction","volume":"274","author":"Chow","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.4049\/jimmunol.166.3.1938","article-title":"MD-2 Enables Toll-Like Receptor 2 (TLR2)-Mediated Responses to Lipopolysaccharide and Enhances TLR2-Mediated Responses to Gram-Positive and Gram-Negative Bacteria and Their Cell Wall Components","volume":"166","author":"Dziarski","year":"2001","journal-title":"J. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.jsbmb.2014.10.014","article-title":"NEFAs activate the oxidative stress-mediated NF-\u03baB signaling pathway to induce inflammatory response in calf hepatocytes","volume":"145","author":"Shi","year":"2015","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/cdd.2016.148","article-title":"A negative feedback loop of ICER and NF-\u03baB regulates TLR signaling in innate immune responses","volume":"24","author":"Lv","year":"2016","journal-title":"Cell Death Differ."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2687","DOI":"10.1093\/nar\/gkx064","article-title":"TLR4-induced NF-\u03baB and MAPK signaling regulate the IL-6 mRNA stabilizing protein Arid5a","volume":"45","author":"Nyati","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.phymed.2017.10.001","article-title":"The regulatory effect of oxymatrine on the TLR4\/MyD88\/NF-\u03baB signaling pathway in lipopolysaccharide-induced MS1 cells","volume":"36","author":"Lu","year":"2017","journal-title":"Phytomedicine"},{"key":"ref_16","first-page":"1155","article-title":"Schizandrin B protects LPS-induced sepsis via TLR4\/NF-\u03baB\/MyD88 signaling pathway","volume":"10","author":"Xu","year":"2018","journal-title":"Am. J. Transl. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/ni.1863","article-title":"The role of pattern-recognition receptors in innate immunity: Update on Toll-like receptors","volume":"11","author":"Kawai","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7059","DOI":"10.1074\/jbc.M109537200","article-title":"Negative Regulation of Toll-like Receptor-mediated Signaling by Tollip","volume":"277","author":"Zhang","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1016\/j.cub.2006.09.062","article-title":"Intracellular Trafficking of Interleukin-1 Receptor I Requires Tollip","volume":"16","author":"Brissoni","year":"2006","journal-title":"Curr. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/35014038","article-title":"Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor","volume":"2","author":"Burns","year":"2000","journal-title":"Nat. Cell Biol."},{"key":"ref_21","first-page":"80","article-title":"Action of tea tree oil and cinnamon leaf oil against oral pathogens","volume":"8","author":"Subhashini","year":"2015","journal-title":"Asian J. Pharm. Clin. Res."},{"key":"ref_22","first-page":"802","article-title":"Australian tea tree oil: A natural antiseptic and fungicidal agent","volume":"72","author":"Shemesh","year":"1991","journal-title":"Aust. J. Pharm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1021\/jf00089a027","article-title":"Gas chromatographic quality control for oil of Melaleuca terpinen-4-ol type (Australian tea tree)","volume":"37","author":"Brophy","year":"1989","journal-title":"J. Agric. Food Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1007\/s10886-010-9798-y","article-title":"A Biochemical Interpretation of Terpene Chemotypes in Melaleuca alternifolia","volume":"36","author":"Keszei","year":"2010","journal-title":"J. Chem. Ecol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1007\/s000110050639","article-title":"Terpinen-4-ol, the main component of the essential oil of Melaleuca alternifolia (tea tree oil), suppresses inflammatory mediator production by activated human monocytes","volume":"49","author":"Hart","year":"2000","journal-title":"Inflamm. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/PL00000305","article-title":"Tea tree oil reduces histamine-induced oedema in murine ears","volume":"51","author":"Brand","year":"2002","journal-title":"Inflamm. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s000110050746","article-title":"The water-soluble components of the essential oil of Melaleuca alternifolia (tea tree oil) suppress the production of superoxide by human monocytes, but not neutrophils, activated in vitro","volume":"50","author":"Brand","year":"2001","journal-title":"Inflamm. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1080\/09629350310001633342","article-title":"Suppression of tumor necrosis factor-alpha-induced neutrophil adherence responses by essential oils","volume":"12","author":"Abe","year":"2003","journal-title":"Mediat. Inflamm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1080\/1071576042000220247","article-title":"Anti-inflammatory Effects of Melaleuca alternifolia Essential Oil on Human Polymorphonuclear Neutrophils and Monocytes","volume":"38","author":"Guerry","year":"2004","journal-title":"Free. Radic. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1002\/eji.200737898","article-title":"TLR4 and S1P receptors cooperate to enhance inflammatory cytokine production in human gingival epithelial cells","volume":"38","author":"Eskan","year":"2008","journal-title":"Eur. J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1590\/S1678-77572012000200002","article-title":"Modulation of host cell signaling pathways as a therapeutic approach in periodontal disease","volume":"20","author":"Junior","year":"2012","journal-title":"J. Appl. Oral Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1007\/s00011-014-0749-x","article-title":"Terpinen-4-ol and alpha-terpineol (tea tree oil components) inhibit the production of IL-1\u03b2, IL-6 and IL-10 on human macrophages","volume":"63","author":"Nogueira","year":"2014","journal-title":"Inflamm. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.3389\/fimmu.2019.02042","article-title":"Short-Chain Fatty Acids Regulate the Immune Responses via G Protein-Coupled Receptor 41 in Bovine Rumen Epithelial Cells","volume":"10","author":"Zhan","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s40104-017-0162-8","article-title":"Innate immune responses induced by lipopolysaccharide and lipoteichoic acid in primary goat mammary epithelial cells","volume":"8","author":"Bulgari","year":"2017","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1152\/physiolgenomics.00223.2006","article-title":"Identification of reference genes for quantitative real-time PCR in the bovine mammary gland during the lactation cycle","volume":"29","author":"Bionaz","year":"2007","journal-title":"Physiol. Genom."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"R173","DOI":"10.1152\/ajpregu.00425.2004","article-title":"Functional organization of the bovine rumen epithelium","volume":"288","author":"Graham","year":"2005","journal-title":"Am. J. Physiol. Integr. Comp. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1046\/j.1365-2184.2003.00265.x","article-title":"An in vitro model of epithelial cell growth stimulation in the rodent mammary gland","volume":"36","author":"Ehmann","year":"2003","journal-title":"Cell Prolif."},{"key":"ref_38","first-page":"419","article-title":"Short-chain fatty acids and CO2 as regulators of Na+ and Cl? absorption in isolated sheep rumen mucosa","volume":"161","author":"Vogler","year":"1991","journal-title":"J. Comp. Physiol. B"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.3945\/jn.109.108506","article-title":"Epithelial Capacity for Apical Uptake of Short Chain Fatty Acids Is a Key Determinant for Intraruminal pH and the Susceptibility to Subacute Ruminal Acidosis in Sheep","volume":"139","author":"Penner","year":"2009","journal-title":"J. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s00360-005-0493-1","article-title":"Bicarbonate exporting transporters in the ovine ruminal epithelium","volume":"175","author":"Bilk","year":"2005","journal-title":"J. Comp. Physiol. B"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1007\/s00424-003-1067-2","article-title":"The SLC16 gene family? From monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond","volume":"447","author":"Halestrap","year":"2004","journal-title":"Pfl\u00fcgers Archiv"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.rvsc.2010.06.002","article-title":"Effects of age and concentrate feeding on the expression of MCT 1 and CD147 in the gastrointestinal tract of goats and Hereford finishing beef bulls","volume":"90","author":"Koho","year":"2011","journal-title":"Res. Vet. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.cbpb.2005.03.003","article-title":"Expression of MCT1, MCT2 and MCT4 in the rumen, small intestine and liver of reindeer (Rangifer tarandus tarandus L.)","volume":"141","author":"Koho","year":"2005","journal-title":"Comp. Biochem. Physiol. Part A Mol. Integr. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.gene.2006.12.020","article-title":"Expression, cellular localization, and functional role of monocarboxylate transporter 4 (MCT4) in the gastrointestinal tract of ruminants","volume":"391","author":"Kirat","year":"2007","journal-title":"Gene"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0014-5793(98)00119-7","article-title":"Comparative molecular analysis of Na+\/H+ exchangers: A unified model for Na+\/H+ antiport?","volume":"424","author":"Dibrov","year":"1998","journal-title":"FEBS Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1113\/expphysiol.2005.029959","article-title":"H+-coupled nutrient, micronutrient and drug transporters in the mammalian small intestine","volume":"92","author":"Thwaites","year":"2007","journal-title":"Exp. Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"G1171","DOI":"10.1152\/ajpgi.00099.2006","article-title":"A vH+-ATPase is present in cultured sheep ruminal epithelial cells","volume":"291","author":"Etschmann","year":"2006","journal-title":"Am. J. Physiol.-Gastrointest. Liver Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s00360-007-0221-0","article-title":"Molecular identification, immunolocalization, and functional activity of a vacuolar-type H+-ATPase in bovine rumen epithelium","volume":"178","author":"Albrecht","year":"2007","journal-title":"J. Comp. Physiol. B"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Sejrsen, K., Hvelplund, T., and Nielsen, M.O. (2006). Ruminal SCFA Absorption: Channelling Acids without Harm. Ruminant Physiology: Digestion, Metabolism and Impact of Nutrition on Gene Expression, Immunology and Stress, Wageningen Academic Publishers.","DOI":"10.3920\/978-90-8686-566-6"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"351","DOI":"10.3168\/jds.2010-3435","article-title":"Population structure of rumen Escherichia coli associated with subacute ruminal acidosis (SARA) in dairy cattle","volume":"94","author":"Khafipour","year":"2011","journal-title":"J. Dairy Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"761","DOI":"10.3168\/jds.S0022-0302(06)72137-3","article-title":"Plant Extracts Affect In Vitro Rumen Microbial Fermentation","volume":"89","author":"Busquet","year":"2006","journal-title":"J. Dairy Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2649","DOI":"10.3168\/jds.S0022-0302(06)72341-4","article-title":"Effect of Essential Oil Active Compounds on Rumen Microbial Fermentation and Nutrient Flow in In Vitro Systems","volume":"89","author":"Castillejos","year":"2006","journal-title":"J. Dairy Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.anifeedsci.2005.03.008","article-title":"Screening for the effects of natural plant extracts and secondary plant metabolites on rumen microbial fermentation in continuous culture","volume":"123","author":"Busquet","year":"2005","journal-title":"Anim. Feed Sci. Technol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1046\/j.1365-2133.2002.05034.x","article-title":"Tea tree oil reduces histamine-induced skin inflammation","volume":"147","author":"Koh","year":"2002","journal-title":"Br. J. Dermatol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.jcms.2009.03.017","article-title":"The battle against multi-resistant strains: Renaissance of antimicrobial essential oils as a promising force to fight hospital-acquired infections","volume":"37","author":"Warnke","year":"2009","journal-title":"J. Cranio-Maxillofac. Surg."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40104-020-00468-9","article-title":"The protective roles of tea tree oil extracts in bovine mammary epithelial cells and polymorphonuclear leukocytes","volume":"11","author":"Zhan","year":"2020","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"13479","DOI":"10.1016\/S0021-9258(18)68262-6","article-title":"A family of lipopolysaccharide binding proteins involved in responses to gram-negative sepsis","volume":"263","author":"Tobias","year":"1988","journal-title":"J. Biol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1084\/jem.179.1.269","article-title":"Lipopolysaccharide (LPS)-binding protein accelerates the binding of LPS to CD14","volume":"179","author":"Hailman","year":"1994","journal-title":"J. Exp. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0898-6568(00)00149-2","article-title":"LPS induction of gene expression in human monocytes","volume":"13","author":"Guha","year":"2001","journal-title":"Cell. Signal."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/ar1469","article-title":"Toll-like receptor downstream signaling","volume":"7","author":"Kawai","year":"2005","journal-title":"Arthritis Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1093\/intimm\/dxu081","article-title":"Therapeutic uses of anti-interleukin-6 receptor antibody","volume":"27","author":"Kang","year":"2015","journal-title":"Int. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ijporl.2007.09.005","article-title":"Proinflammatory and immunoregulatory cytokines in the middle ear effusions","volume":"72","author":"Skotnicka","year":"2008","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Le, J., and Vil\u010dek, J. (1990). Interleukin 6: A Multifunctional Cytokine Regulating Immune Reactions and the Acute Phase Protein Response. Pathol. Rev. 1990, 97\u2013111.","DOI":"10.1007\/978-1-4612-0485-5_7"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1002\/jlb.56.5.559","article-title":"Essential involvement of interleukin-8 (IL-8) in acute inflammation","volume":"56","author":"Harada","year":"1994","journal-title":"J. Leukoc. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/j.1749-6632.2012.06786.x","article-title":"Regulation of Toll-like receptor signaling pathways in innate immune responses","volume":"1283","author":"Cheng","year":"2013","journal-title":"Ann. N. Y. Acad. Ences"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1146\/annurev.immunol.18.1.217","article-title":"The Biology of Chemokines and their Receptors","volume":"18","author":"Rossi","year":"2000","journal-title":"Annu. Rev. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"R112","DOI":"10.1186\/ar2510","article-title":"Association of elevated transcript levels of interferon-inducible chemokines with disease activity and organ damage in systemic lupus erythematosus patients","volume":"10","author":"Fu","year":"2008","journal-title":"Arthritis Res. Ther."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/11\/8\/2460\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:48:44Z","timestamp":1760165324000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/11\/8\/2460"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,21]]},"references-count":67,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["ani11082460"],"URL":"https:\/\/doi.org\/10.3390\/ani11082460","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,21]]}}}