Lack of Toll-Like Receptor 4 Expression in the Oviductal Epithelial Cells: The Protective Mucosal Immunity of the Human Fallopian Tube Against Bacterial Infection

Abstract

The aim of the study is to evaluate the site-specific immunoregulatory mechanisms against bacterial infection in the human fallopian tubes. We investigated the effects of lipopolysaccharide (LPS) and proinflammatory cytokines on the production of CXC chemokines by cultured oviductal epithelial cells (OEC) and oviductal stromal fibroblasts (OSF) using enzyme-linked immunosorbent assays and western blot analysis. Normal oviducts were obtained from premenopausal patients who had undergone sterilization or hysterectomies for leiomyoma.To study the production of granulocyte chemotactic protein-2 (GCP-2), growth-regulated oncogene α (GROα), and epithelial neutrophil activating peptide-78 (ENA-78) by OEC and OSF. The supernatant was then replaced with recombinant human TNF-α, recombinant human IL-1β, and LPS. The expression of the toll-like receptor (TLR) 4 and others were observed by western blot analysis. LPS stimulated the secretion of GCP-2, GROα, and ENA-78 by OSF, but not by OEC. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) also stimulated these chemokine secretions by both OEC and OSF. The expression of the TLR4 was detected only in OSF, but not in OEC. The CD14 expression was not detected in either OEC or OSF. A significant expression of the TNF-receptor (TNFR) I, TNFRII, the IL-1 receptor (IL-1R) I, and IL-1RII were detected in both OEC and OSF. The phosphorylation of the inhibitor kB-α (IκB-α) protein was not detected in OEC after stimulation by LPS, whereas IκB-α phosphorylation was observed after stimulation by TNF-α or IL-1β in these cells. However, IκB-α phosphorylation was observed in OSF after stimulation by either LPS, TNF-α, or IL-1β. These results suggest that epithelial cells and fibroblasts in the human fallopian tube have evolved aunique, site-specific mechanism for recognizing Gram-negative pathogens. The lack of TLR4 in OEC may be important for avoiding a state of unnecessary inflammation that could disrupt the epithelial barrier and cause irreversible tubal scarring.