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. 2023 Nov 1;24(21):15875. doi: 10.3390/ijms242115875

Figure 5.

Figure 5

Inflammatory signaling pathways that produce chemokines during cardiorenal syndrome type 4 (CRS type 4). Factors and molecules the kidney releases during chronic kidney disease (CKD) activate inflammation-related signaling pathways. These pathways comprise Toll-like receptors (TLRs) 2, 4, and 9, the stimulator of interferon genes (STING), and NOD-like receptor (NLR) family pyrin domain containing 3 (NLRP3), which mediate the activation of p65/c-Rel, inducing the activation of nuclear factor kappa B (NF-κB) into the nucleus. Moreover, mitochondrial reactive oxygen species (mtROS) stimulates this transcription factor. NF-κB activation induces the production of inflammatory genes like tumor necrosis factor α (TNF-α), proinflammatory interleukins (IL): IL-1β, IL-18, IL-6, and chemokines (CCL2, CCL8, and CXCL10). These chemokines attract inflammatory cells (macrophages, neutrophils, and T cells) to the tissue, aggravating inflammation. Using chemokine inhibitors during CKD might be an excellent strategy to prevent CRS type 4. cGAS: cyclic guanosine monophosphate (cGMP)–adenosine monophosphate (AMP) synthase, mtDNA: mitochondrial deoxyribonucleic acid, HSPs = heat shock proteins, ATP = adenosine triphosphate, TNFR: tumor necrosis factor receptor, P2YRs and P2XRs: purinergic receptor. Symbols: red and blue ↑ mean an increase. Figure created using BioRender.com.