TLR4–RAGE crosstalk participates in the HG-enhanced LPS-induced inflammation in BAMs (created with BioRender

Schematic representation of the TLR4–RAGE crosstalk participates in the HG-enhanced LPS-induced inflammation in BAMs (created with BioRender.com). HG firstly upregulated the levels of RAGE and TLR4 genes and protein expression in the BAM membrane and the secretion of pro-inflammatory-related mediators (such as HMGB1, S100A8/9, and AGEs) through the ROS/NF-κB pathway. Then, pro-inflammatory-related mediators bind to RAGE and TLR4, causing RAGE–TLR4 crosstalk (increasing the levels of RAGE and TLR4) to synergistically activate the downstream MyD88/NF-κB signaling pathway and promote the release of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. When HG acts together with LPS, HG upregulates the levels of RAGE and TLR4 genes and protein expression, which can provide more receptor sites for LPS binding, and the LPS also upregulates the levels of RAGE and TLR4 genes and protein expression that can offer more receptor sites for pro-inflammatory-related mediators. The combination of HG and LPS through RAGE–TLR4 crosstalk further activates the downstream MyD88/NF-κB signaling pathway and exacerbates pro-inflammatory cytokine release in BAMs.

Publication

RAGE–TLR4 Crosstalk Is the Key Mechanism by Which High Glucose Enhances the Lipopolysaccharide-Induced Inflammatory Response in Primary Bovine Alveolar Macrophages (2023) Longfei Yan, et al. Int J Mol Sci. 2023 Apr;24(8). Figure: F6. Homo sapiens

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