Tripartite motif 22 (TRIM22) downregulates TLR3-induced CCL5 expression in human renal proximal tubular epithelial cells

BackgroundTripartite motif 22 (TRIM22) plays a key role in viral defense by suppressing replication. Kidney transplant recipients and patients with chronic kidney disease are compromised hosts and susceptible to viral infections. Although several viruses that infect the renal tubules have been identified, the function and role of TRIM22 in viral infections of the renal tubules remain unknown. Tubular epithelial cells express Toll-like receptors (TLRs), which are pattern recognition receptors. Notably, TLR3 recognizes viral RNA and induces the release of type I interferons (IFNs) and subsequently several proinflammatory chemokines, such as IFN-beta and C-C motif chemokine ligand 5 (CCL5). This study investigated the role of TRIM22 in TLR3-induced CCL5 expression in cultured human renal proximal tubular epithelial cells (hRPTECs).Methods and resultshRPTECs were treated with polyinosinic-polycytidylic acid (poly IC), a ligand for TLR3. Reverse transcription-quantitative polymerase chain reaction was used to analyze mRNA expression, and western blotting and enzyme-linked immunosorbent assays were used to analyze protein expression. Poly IC-induced TRIM22 mRNA and protein expression increased in concentration- and time-dependent manners. Cells were transfected with small interfering RNA against IFN-beta or TRIM22 to knock down their respective expression. Knockdown of IFN-beta attenuated poly IC-induced TRIM22 mRNA and protein expression. Whereas TRIM22 knockdown upregulated poly IC-induced CCL5 mRNA and protein expression.ConclusionOur results revealed the TLR3-IFN-beta-TRIM22 pathways in hRPTECs. TRIM22 suppressed TLR3-induced CCL5 expression, suggesting that TRIM22 suppresses viral infection-induced excessive inflammation in addition to direct antiviral defense.