FimH of uropathogenic Escherichia coli influenced the infection in prostate cells by the modulation of JAK/STAT signaling pathway

Abstract Background: The FimH expression may be a key factor affecting prostatitis caused by UPEC infection. Whether its regulation by the JAK/STAT pathway increases resistance to inflammation caused by infection with high FimH-expressing UPEC strains requires investigation. Methods: The effect of FimH on the ability of knockout ΔFimH UPEC, FimHover -expressed UPEC, and wild-type strains to invade prostate cells and induce inflammation and the effects of different FimH levels on testosterone-treated UPEC and regulation of the JAK/STAT pathway were analyzed. Results: Comparison of the three strains revealed the inhibitory effects of testosterone were more significant in the ΔFimH strain. Testosterone-pretreated ΔFimH UPEC showed weak inflammatory responses and JAK/STAT expression. FimHover UPEC better resisted the inhibitory effects of testosterone, which there was no significantly decreases except 20 μg/ml pretreated group in most JAK/STAT-related proteins. The effects of FimH showed a concentration-dependent response to testosterone, particularly to JAK1, STAT3, and pSTAT3, which also affected the subsequent expression of TLR4, IL-6, and IFN-γ. It has been suggested that regulation of the JAK1/STAT3 pathway may be associated with the effects of the FimH virulence factor on the inhibition of testosterone in UPEC infection. Conclusion: The inhibitory effect of testosterone on UPEC infection in prostate epithelial cells was affected by the virulence factor FimH of UPEC, and reduced the production of inflammatory factors. The JAK/STAT pathway plays a key role in regulating UPEC infection and influences testosterone suppression responses in prostate cells. Our study provides a possible guideline for using testosterone to treat clinical recurrent UPEC infection and persistent prostatitis.