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Chronic kidney disease induces inflammation by increasing Toll–like receptor–4, cytokine and cathelicidin expression in neutrophils and monocytes

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ABSTRACT TLR expression in neutrophils and monocytes is associated with increased cytokine synthesis, resulting in increased inflammation. However, the inflammatory pathway related to TLR and cathelicidin expression in these cells… Click to show full abstract

ABSTRACT TLR expression in neutrophils and monocytes is associated with increased cytokine synthesis, resulting in increased inflammation. However, the inflammatory pathway related to TLR and cathelicidin expression in these cells from CKD patients is unclear. To evaluate TLR4, cathelicidin, TNF–&agr;, IL–6, IL–10 and MCP–1 expression in neutrophils and monocytes from HD and CKD patients. Blood samples were drawn from 47 CKD and 43 HD patients and 71 age and gender–matched healthy volunteers (CONT). TLR4 was analyzed using flow cytometry. Cathelicidin, TNF–&agr;, IL–6, IL–10 and MCP–1 were analyzed via ELISA.TLR4 expression in neutrophils was higher in HD patients than in stage 3 and 4 CKD patients. In these cells, we observed a positive correlation between TLR4 and cathelicidin, TNF–&agr;, IL–6, IL–10 and MCP–1 levels. In monocytes, TLR4 expression was significantly higher in CKD 3 and 4 groups than in the control and HD groups and positively and negatively correlated with IL–6 and MCP–1 and cathelicidin, respectively. TNF–&agr;, IL–6 and MCP–1 serum levels were higher in HD and CKD patients than in control. Cathelicidin and IL–10 levels were only higher in HD patients. IL–6 serum levels were positively correlated with all cytokines, and cathelicidin was negatively correlated with MCP–1 (r = − 0.35; p < 0.01) and positively correlated with IL–10 (r = 0.37; p = 0.001). These results suggest that a uremic environment induces high TLR4, cathelicidin and cytokine expression and may increase inflammation. Thus, future studies should be conducted to evaluate whether TLR4 and cathelicidin should be targets for anti–inflammatory therapeutic strategies. HIGHLIGHTSExpression of TLR4 in neutrophils was higher in HD than CKD patients.Expression of TLR4 in monocytes was higher in CKD than HD patients.CKD and HD patients have high levels of TNF–&agr;, IL–6, IL–10, MCP–1 and cathelicidin.TLR4 had a correlation between TNF–&agr;, IL–6, IL–10 MCP–1 and cathelicidin.The uremic environment induces inflammation by TLR4, cathelicidin and cytokine activation.

Keywords: ckd patients; mcp; expression; expression neutrophils; tlr4; cathelicidin

Journal Title: Experimental Cell Research
Year Published: 2018

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