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Toll\u2010like receptors (TLRs) are essential to orchestrate immune responses against bacterial infections. The epididymis displays region\u2010specific inflammatory responses to bacterial\u2010derived TLR agonists, such as lipopolysaccharide (LPS; TLR4 agonist) and lipoteichoic acid (LTA; TLR2\/TLR6 agonist), suggesting that TLR\u2010associated signaling pathways could influence the magnitude of inflammatory responses in epididymitis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate the expression and regulation of key genes associated with TLR4 and TLR2\/TLR6 signaling pathways during epididymitis induced by UPEC, LPS, and LTA in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and methods<\/jats:title>\n                    <jats:p>Epididymitis was induced in mice using UPEC, ultrapure LPS, or LTA, injected into the interstitial space of the initial segment or the lumen of the vas deferens close to the cauda epididymidis. Samples were harvested after 1, 5, and 10 days for UPEC\u2010treated animals and 6 and 24\u00a0h for LPS\u2010\/LTA\u2010treated animals. Ex vivo epididymitis was induced by incubating epididymal regions from naive mice with LPS or LTA. RT\u2010qPCR and Western blot assays were conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      UPEC infection up\u2010regulated\n                      <jats:italic>Tlr2<\/jats:italic>\n                      ,\n                      <jats:italic>Tlr4<\/jats:italic>\n                      , and\n                      <jats:italic>Tlr6<\/jats:italic>\n                      transcripts and their associated signaling molecules\n                      <jats:italic>Cd14<\/jats:italic>\n                      ,\n                      <jats:italic>Ticam1<\/jats:italic>\n                      , and\n                      <jats:italic>Traf6<\/jats:italic>\n                      in the cauda epididymidis but not in the initial segment. In these epididymal regions, LPS and LTA differentially modulated\n                      <jats:italic>Tlr2<\/jats:italic>\n                      ,\n                      <jats:italic>Tlr4<\/jats:italic>\n                      ,\n                      <jats:italic>Tlr6<\/jats:italic>\n                      ,\n                      <jats:italic>Cd14<\/jats:italic>\n                      ,\n                      <jats:italic>Myd88<\/jats:italic>\n                      ,\n                      <jats:italic>Ticam1<\/jats:italic>\n                      ,\n                      <jats:italic>Traf3<\/jats:italic>\n                      , and\n                      <jats:italic>Traf6<\/jats:italic>\n                      expression levels. NFKB and AP1 activation was required for LPS\u2010 and LTA\u2010induced up\u2010regulation of TLR\u2010associated signaling transcripts in the cauda epididymidis and initial segment, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The dynamic modulation of TLR4 and TLR2\/TLR6 signaling pathways gene expression during epididymitis indicates bacterial\u2010derived antigens elicit an increased tissue sensitivity to combat microbial infection in a spatial manner in the epididymis. Differential activation of TLR\u2010associated signaling pathways may contribute to fine\u2010tuning inflammatory responses along the epididymis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.13630","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T05:28:59Z","timestamp":1710739739000},"page":"1024-1037","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Regional modulation of toll\u2010like receptor signaling pathway genes in acute epididymitis in mice"],"prefix":"10.1111","volume":"12","author":[{"given":"Alexandre D.","family":"Andrade","sequence":"first","affiliation":[{"name":"Department of Biophysics and Pharmacology Institute of Biosciences of Botucatu S\u00e3o Paulo State University, Botucatu  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscila G. 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