IFIT Proteins Are Involved in CXCL10 Expression in Human Glomerular Endothelial Cells Treated with a Toll-Like Receptor 3 Agonist

Abstract

Introduction: Various viruses including a novel coronavirus (SARS-CoV-2) can infect the kidney. When viruses invade the glomeruli from the bloodstream, glomerular endothelial cells (GECs) initiate the innate immune reactions. We investigated the expression of interferon (IFN)-induced protein with tetratricopeptide repeats (IFIT) 1/2/3, antiviral molecules, in human GECs treated with a toll-like receptor (TLR) 3 agonist. Role of IFIT1/2/3 in the expression of C-X-C motif chemokine ligand 10 (CXCL10) was also examined. Methods: Human GECs were cultured and stimulated with polyinosinic-polycytidylic acid (poly IC), a synthetic TLR3 agonist. Real-time qPCR, Western blotting, and ELISA were used to examine the expression of IFIT1/2/3, IFN-β, and CXCL10. RNA interference against IFN-β or IFIT1/2/3 was also performed. Results: Expression of IFIT1/2/3 and CXCL10 was induced by poly IC in GECs. The inductions were inhibited by RNA interfering of IFN-β. Knockdown of IFIT1/2/3 decreased the CXCL10 expression. Knockdown of IFIT3 decreased the expression of IFIT1 and IFIT2 proteins. Conclusion: IFIT1/2/3 and CXCL10 were induced by poly IC via IFN-β in GECs. IFIT1/2/3 may increase the expression of CXCL10 which induces lymphocyte chemotaxis and may inhibit the replication of infected viruses. These molecules may play a role in GEC innate immune reactions in response to viruses.

The emerging roles of IFIT3 in antiviral innate immunity and cellular biology

“…IFIT3 positively regulates IFN‐β and the OAS RNase L pathway to degrade RNA to inhibit KSHV lytic replication, in addition to potentially directly targeting viral mRNA 10,11 . IFIT3 may increase the expression of CXCL10 that induces lymphocyte chemotaxis and inhibits the replication of virus 49 . IFIT3 induces IFN signaling pathway and represses adenoviral immediate early gene expression 42 .…”

Mucosal Gene Expression in Response to SARS-CoV-2 Is Associated with Viral Load

“…IFIT genes, particularly IFIT1, work in concert with other ISGs to inhibit viral translation by binding viral mRNAs that mimic host mRNAs due to the presence of 5′ cap-1 structures ( 33 , 34 ), which SARS-CoV-2 contains ( 35 ). The IFIT proteins also increase the expression of CXCL10 ( 36 ), the 2nd most upregulated gene in our analysis, which induces lymphocyte chemotaxis and may inhibit the replication of infected viruses. Only one study has identified IFIT1 in vitro during COVID-19 infection ( 37 ).…”

Mucosal gene expression in response to SARS-CoV-2 is associated with early viral load

“…IFIT genes, particularly IFIT1, work in concert with other ISGs to inhibit viral translation by binding viral mRNAs that mimic host mRNAs due to presence of 5’ cap-1 structures [33, 34], which SARS-CoV-2 contains [35]. IFIT proteins also increase the expression of CXCL10,[36] the 2 nd most upregulated gene in our analysis, which induces lymphocyte chemotaxis and may inhibit the replication of infected viruses. Only one study has identified IFIT1 during COVID-19 in vitro [37].…”