Signalling pathways associated with IL-6 production and epithelial-mesenchymal transition induction in prostate...

Area of Science:

• Urology
• Infectious Diseases
• Cell Biology

Background:

• Trichomonas vaginalis (Tv) is linked to benign prostatic hyperplasia (BPH) and chronic prostatitis.
• Elevated IL-6 levels are associated with prostate inflammation and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).
• Pathogen-induced inflammation can drive epithelial-mesenchymal transition (EMT).

Purpose of the Study:

• To investigate IL-6 production in human prostate epithelial cells (PECs) stimulated by Tv.
• To determine if Tv infection induces EMT in PECs.
• To identify signaling pathways involved in Tv-induced IL-6 production and EMT.

Main Methods:

• PECs were stimulated with Tv.
• IL-6 production, TLR2/4, MAPK, NF-κB, JAK2/STAT3, and ROS levels were measured.
• EMT markers (epithelial and mesenchymal) were assessed via transcript analysis.
• Inhibitors of TLRs, ROS, MAPKs, NF-κB, and JAK were used to block signaling pathways.

Main Results:

• Tv stimulation increased IL-6 production, TLR2/4, MAPKs, NF-κB, JAK2/STAT3, and ROS in PECs.
• Inhibition of TLR2/4, ROS, MAPKs, NF-κB, or JAK pathways reduced IL-6 production.
• Tv exposure led to decreased epithelial markers and increased mesenchymal markers, indicating EMT.
• JAK and NF-κB inhibition suppressed Tv-induced EMT.

Conclusions:

• Tv infection stimulates IL-6 production in PECs via TLR2/4, MAPKs, NF-κB, JAK2/STAT3, and ROS.
• Tv infection induces EMT in PECs, a process dependent on JAK and NF-κB signaling.
• These findings suggest Tv may contribute to prostate pathologies through inflammation and EMT.