Abstract: In this study, we aimed to investigate whether high glucose regulates proinflammatory cytokine IL-1β, IL-6 and TNF-α release from bovine alveolar macrophages (BAMs) through RAGE-TLR4 crosstalk. BAMs were randomly divided into normal glucose group (NG), high glucose group (HG), high glucose + RAGE inhibitor group (H + F), high glucose + TLR4 inhibitor group (H + T) and DMSO group, and the supernatant and lower cells were collected after 12 h of treatment. The mRNA and protein expression of RAGE, TLR4, MyD88 and NF-κB p65 were detected by qRT-PCR and Western blot, and the concentrations of TNF-α, IL-1β and IL-6 in the supernatant were detected by ELISA. The levels of mRNA and protein expression of RAGE, TLR4, MyD88 and NF-κB p65 and the concentrations of IL-1β, IL-6 and TNF-α in the supernatant of HG group were significantly higher than those of NG group, H+F group and H+T group (P<0.01); the levels of mRNA and protein of MyD88, NF-κB p65 and RAGE and the concentrations of three proinflammatory cytokines in the supernatant of H+F group and H+T group were significantly higher than those of NG group (P<0.05, P<0.01). Our results suggest that high glucose can cause the release of proinflammatory cytokines IL-1β, IL-6 and TNF-α from bovine alveolar macrophages via RAGE-TLR4 crosstalk, which further elucidated the molecular mechanism of high glucose promoted the inflammatory response in bovine alveolar macrophages.

Key words: inflammatory signaling pathway, RAGE-TLR4 crosstalk, bovine alveolar macrophage, high glucose