Cationic ribosomal proteins can inhibit pro‐inflammatory action stimulated by LPS+HMGB1 and are hindered by advanced glycation end products

Abstract

AbstractWe previously found that ribosomal protein L9 (RPL9) is a novel advanced glycation end product (AGE)‐binding protein that can decrease pro‐inflammatory TNF‐α expression stimulated by lipopolysaccharide (LPS) plus high‐mobility group box 1 (HMGB1), suggesting that RPL9 has a role in regulating LPS+HMGB1‐stimulated inflammatory reactions. Among the various ribosomal proteins, it was found that RPS5 reproduced the regulatory activity of RPL9 on LPS+HMGB1‐stimulated TNF‐α expression in macrophage‐like RAW264.7 cells. RPL9 and RPS5 share a common feature as cationic proteins. Polylysine, a cationic polypeptide, and a synthetic peptide of the cationic region from RPL9 also exhibited reducing activity on LPS+HMGB1‐induced TNF‐α expression. By pull‐down assay, RPL9 and RPS5 were confirmed to interact with AGEs. When AGEs coexisted with LPS, HMGB1, plus RPL9 or RPS5, the reducing effect of TNF‐α expression by these cationic ribosomal proteins was shown to be abrogated. The results suggest that cationic ribosomal proteins have a regulatory role in the pro‐inflammatory response induced by LPS+HMGB1, and in the pathophysiological condition of accumulating AGEs, this regulatory effect is abolished, which exacerbates inflammation.