Pattern recognition receptor-initiated innate immune responses in mouse prostatic epithelial cells‡

Area of Science:

• Immunology
• Urology
• Molecular Biology

Background:

• Prostate pathologies such as benign prostatic hyperplasia, prostate cancer, and prostatitis are associated with local inflammation.
• The precise mechanisms initiating prostate inflammation are not fully understood.
• Innate immune responses in tissue-specific cells are implicated in local inflammation.

Purpose of the Study:

• To investigate pattern recognition receptor (PRR)-initiated innate immune responses in mouse prostatic epithelial cells (PECs).
• To elucidate the specific responses triggered by different PRR ligands in the prostate.

Main Methods:

• Primary mouse PECs were analyzed for the expression of pattern recognition receptors (PRRs).
• PECs were stimulated with various PRR ligands, including lipopolysaccharide (LPS), flagellin, polyinosinic-polycytidylic acid (poly(I:C)), and a herpes simplex virus DNA analog (HSV60).
• Gene expression of inflammatory cytokines, chemokines, type 1 interferons, and antiviral proteins was quantified.

Main Results:

• Mouse PECs expressed Toll-like receptor 3 (TLR3), TLR4, TLR5, melanoma differentiation-associated protein 5 (MDA5), and IFN-inducible protein 16 (p204).
• LPS and flagellin induced inflammatory cytokines (TNF-α, IL-6) and chemokines (MCP-1, CXCL10).
• Poly(I:C) and HSV60 induced type 1 interferons (IFN-α, IFN-β) and antiviral proteins, inhibiting mumps virus replication.

Conclusions:

• Prostatic epithelial cells possess a functional innate immune system mediated by PRRs.
• Distinct PRR activation pathways lead to either pro-inflammatory cytokine or type 1 interferon responses.
• These findings provide crucial insights into the initiation of prostate inflammation and potential therapeutic strategies.