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Signalling pathways associated with IL ‐6 production and epithelial–mesenchymal transition induction in prostate epithelial cells stimulated with Trichomonas vaginalis
Author(s) -
Han I. H.,
Kim J. H.,
Kim S. S.,
Ahn M. H.,
Ryu J. S.
Publication year - 2016
Publication title -
parasite immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 75
eISSN - 1365-3024
pISSN - 0141-9838
DOI - 10.1111/pim.12357
Subject(s) - epithelial–mesenchymal transition , prostatitis , cancer research , prostate cancer , trichomonas vaginalis , inflammation , prostate , mapk/erk pathway , mesenchymal stem cell , biology , hyperplasia , immunology , signal transduction , medicine , endocrinology , cancer , metastasis , microbiology and biotechnology
Summary Trichomonas vaginalis (Tv) has been found in patient tissue of benign prostatic hyperplasia ( BPH ), and suggested to cause chronic prostatitis. IL ‐6 is known as one of the important factors of chronic inflammation in prostate cancer. Patients with chronic prostatitis/chronic pelvic pain syndrome ( CP / CPPS ) had higher levels of IL ‐6 in seminal plasma. Furthermore, inflammatory conditions induced by pathogen infections have been shown to promote epithelial–mesenchymal transition ( EMT ). Here, we investigated the signals involved in IL ‐6 production by human prostate epithelial cells ( PEC s) stimulated with Tv and examined whether Tv induces EMT in PEC s. We found that PEC s stimulated with Tv increased the production of IL ‐6, as well as the expression of TLR 2, TLR 4, MAPK s (p38, JNK , ERK ), NF ‐κB and JAK 2/ STAT 3, and levels of ROS . Inhibition of TLR 2 or TLR 4 reduced IL ‐6 production as well as expression of these other factors, and agents inhibiting ROS , MAPK s, NF ‐κB and JAK reduced IL ‐6 production. However, when PEC s were stimulated with Tv , transcripts of mesenchymal cell markers increased, and epithelial cell markers decreased. In addition, the induction of EMT was suppressed by inhibitors of JAK or NF ‐κB. These findings are the first evidence that Tv infection of prostate epithelial cells may induce EMT .