TLR4 pathway is hypersensitive to lipopolysaccharide in patients with chronic suppurative otitis media

Abstract

Background: Chronic Suppurative Otitis Media (CSOM) is an uncontrolled inflammation in the middle ear due to bacterial infections and has been linked to the overactivation of the Toll-Like Receptor 4 (TLR4) pathway. The pathway is activated by Lipopolysaccharide (LPS) released from the gram-negative bacterial cell wall. Currently, there is limited information about the factors responsible for overactivation. One possible factor could be the hypersensitivity of the TLR4 pathway in CSOM patients. Aim and Objectives: To evaluate the effect of LPS on the expression of key markers of the TLR4 pathway viz.,TLR4, Nuclear Factor kappa B (NFkB), and Tumor Necrosis Factor α (TNFα) in CSOM. Material and Methods: A case-control study was carried out in patients with CSOM and healthy participants (n = 63). Peripheral blood mononuclear cells from the participants were cultured for 4h in the presence of LPS. TLR4 and NFkB genes expression was measured in the cell pellet by using qPCR. TNFα cytokine levels were measured in the conditioned media by using ELISA. Fold change expression of genes between LPS-treated and untreated samples was calculated and compared using statistical methods. Results: LPS-induced fold change in the expression of TLR4 (2.8 vs. 1.6; p < 0.001) and NFkB genes (3.8 vs. 1.4; p < 0.001) were higher in the CSOM group compared to the control group. Furthermore, LPS-induced fold change in TNFα production was higher in the CSOM group compared to the control group (3.2 vs. 1.1; p < 0.001). Conclusion: Overall results indicate that the LPS treatment resulted in comparatively higher expression of the selected genes, indicating hypersensitivity of the TLR4 pathway in CSOM patients.

Keywords

• chronic suppurative otitis media
• lipopolysaccharide
• toll-like receptor 4
• tumor necrosis factor
• nuclear factor kappa b