{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T12:18:18Z","timestamp":1794313098809,"version":"4.9.0"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,5,12]],"date-time":"2006-05-12T00:00:00Z","timestamp":1147392000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2006,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Toll\u2010like receptors (TLRs) are pattern recognition receptors (PRRs) that recognize conserved pathogen\u2010associated molecular patterns (PAMPs) synthesized by micro\u2010organisms. Despite the essential requirement for TLRs in prokaryotic infection, the pattern and regulation of<jats:italic>TLR<\/jats:italic>gene expression by<jats:italic>Trichomonas vaginalis<\/jats:italic>in the mucocutaneous barrier are still unknown. Our hypothesis is that<jats:italic>T.\u2003vaginalis<\/jats:italic>\u2010infected epithelial cells are major effector cells in the skin barrier. These cells function as a central regulator of<jats:italic>TLR<\/jats:italic>gene expression, thus accelerating the process of barrier dysfunction via increased release of chemokines and proinflammatory cytokines. To test this hypothesis, RT\u2010PCR was performed on<jats:italic>TLR<\/jats:italic>s, interleukin (<jats:italic>IL<\/jats:italic>)\u20108 and tumour necrosis factor (<jats:italic>TNF<\/jats:italic>)\u2010\u03b1. Stimulation of HeLa cells by<jats:italic>T.\u2003vaginalis<\/jats:italic>was observed to up\u2010regulate<jats:italic>TLR2<\/jats:italic>,<jats:italic>4<\/jats:italic>and<jats:italic>9<\/jats:italic>mRNA expression as well as that of<jats:italic>IL\u20108<\/jats:italic>and<jats:italic>TNF\u2010\u03b1<\/jats:italic>. To further clarify the molecular mechanism of barrier devastation triggered by these up\u2010regulatory stimuli, we examined the profiles of extracellular signal\u2010regulated kinase (ERK), p38 mitogen\u2010activated protein kinase (MAPK) and nuclear factor (NF)\u2010\u03baB activation in HeLa cells using specific inhibitors. Interestingly, pretreatment of HeLa cells with the p38 MAPK inhibitor SB203580 demonstrated inhibition of<jats:italic>T.\u2003vaginalis<\/jats:italic>\u2010induced up\u2010regulation of<jats:italic>TLR2<\/jats:italic>,<jats:italic>4<\/jats:italic>, and<jats:italic>9<\/jats:italic>mRNA expression. By contrast, inhibition of ERK or NF\u2010\u03baB activation failed to block<jats:italic>T.\u2003vaginalis<\/jats:italic>\u2010induced up\u2010regulation of<jats:italic>TLR9<\/jats:italic>mRNA expression or<jats:italic>TLR2<\/jats:italic>and<jats:italic>TLR4<\/jats:italic>mRNA expression, respectively. In addition, pretreatment with SB203580 reduced epithelium\u2010derived IL\u20108 and TNF\u2010\u03b1 release evoked by<jats:italic>T.\u2003vaginalis<\/jats:italic>. Our results show that<jats:italic>T.\u2003vaginalis<\/jats:italic>infection of the mucocutaneous barrier could up\u2010regulate<jats:italic>TLR2<\/jats:italic>,<jats:italic>4<\/jats:italic>and<jats:italic>9<\/jats:italic>gene expression via the p38 MAPK signalling pathway in epithelial cells; this process then leads to modulation of p38 MAPK\u2010dependent IL\u20108 and TNF\u2010\u03b1 release from the epithelium.<\/jats:p>","DOI":"10.1111\/j.1365-2567.2006.02347.x","type":"journal-article","created":{"date-parts":[[2006,5,12]],"date-time":"2006-05-12T15:19:04Z","timestamp":1147447144000},"page":"164-170","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Dependence on p38 MAPK signalling in the up\u2010regulation of<i>TLR2<\/i>,<i>TLR4<\/i>and<i>TLR9<\/i>gene expression in<i>Trichomonas vaginalis<\/i>\u2010treated HeLa 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