DEC1 negatively regulates the expression of CXCL10 and CCL5 induced by poly IC in normal human mesangial cells

Abstract

The functions of differentiated embryonic chondrocyte gene (DEC) 1, a basic helix-loop-helix (bHLH) transcription factor, have been reported to be associated with the regulation of mammalian circadian rhythms, differentiation of chondrocytes and skeletal muscles, apoptosis, hypoxia-induced reactions and epithelial mesenchymal transition. Our previous report showed that another bHLH transcription factor DEC2 constitutes a negative feedback loop in Toll-like receptor 3 (TLR3)/interferon (IFN)-β-mediated inflammatory responses in human mesangial cells. However, the role of DEC1 in innate immune responses remains unclear. We have previously reported TLR3/IFN-β/retinoic acid-inducible gene-I (RIG-I)/CCL5 and TLR3/IFN-β/melanoma differentiation-associated gene 5 (MDA5)/CXCL10 axes in cultured normal human mesangial cells treated with polyinosinic-polycytidylic acid (poly IC), a synthetic double-stranded RNA that is sensed by TLR3. The present study was carried out to examine the involvement of DEC1 in these axes. DEC1 was constitutively expressed in human mesangial cells, and the expression was not altered by treatment with poly IC. Interestingly, RNA interference against DEC1 markedly enhanced the poly IC-induced expression of chemokines CXCL10 and CCL5. Knockdown of DEC1 increased the poly IC-induced MDA5 and RIG-I protein expression without affecting mRNA expression, and did not affect phosphorylation of signal transducer and transcription 1 (STAT1). DEC1 may serve as an anti-inflammatory factor by negative regulation of MDA5/CXCL10 and RIG-I/CCL5 in human mesangial cells treated with poly IC.