Carbon monoxide inhibits human bronchial epithelial CCL5 and IL-6 secretion induced by SARS-CoV-2 spike RBD protein

Abstract

Carbon monoxide (CO) is a novel anti-inflammatory molecule, but the effects of CO on SARS-CoV-2 spike RBD (S-RBD)-induced human bronchial epithelial cytokines release remains unclear. CO was delivered using CO-releasing molecule 3 (CORM-3). The effects of S-RBD, ATPγS and CO on cytokines secretion were determined by enzyme-linked immunosorbent assay (ELISA) in 16HBE14o-human bronchial epithelial cell line. The inhibitory effect of CO on S-RBD-induced ERK phosphorylation was assessed by Western blot analysis. The regulatory effect of CO on extracellular nucleotide-induced ion transport was quantified by short-circuit current (I_SC). S-RBD evoked CCL5 and IL-6 release and this effect could be suppressed by CO. However, CO failed to inhibit ATP release induced by S-RBD while decreased ATP-induced CCL5 and IL-6 secretion as well as ion transport. Furthermore, CO significantly inhibited ERK phosphorylation induced by S-RBD. These findings suggest an anti-inflammatory role of CO during inflammation induced by S-RBD and extracellular nucleotide in human bronchiol epithelial cells.