PORF5 plasmid protein of Chlamydia trachomatis induces MAPK-mediated pro-inflammatory cytokines via TLR2 activation in THP-1 cells.

Infection with Chlamydia trachomatis induces inflammatory pathologies in the urogenital tract that can lead to infertility and ectopic pregnancy. Pathogenesis of infection has been mostly attributed to excessive cytokine production. However, precise mechanisms on how C. trachomatis triggers this production, and which protein(s) stimulate inflammatory cytokines remains unknown. In the present study, the C. trachomatis pORF5 protein induced tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-8 (IL-8) in dose- and time-dependent manners in the THP-1 human monocyte cell line. We found that intracellular p38/mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK)/MAPK signaling pathways were required for the induction of TNF-α, IL-1β and IL-8. Blockade of toll-like receptor 2 (TLR2) signaling reduced induction levels of TNF-α, IL-8 and IL-1β. We concluded that the C. trachomatis pORF5 protein might contribute to the inflammatory processes associated with chlamydial infections.