Circular RNA hsa_circ_0099188 Regulates Inducible Nitric Oxide Synthase and Chemokine Transcription in Macrophages by Targeting the hsa-miR-381-3p/PPP3CA and hsa-miR-381-3p/KLF4 Pathways in Response to 4,4’-Methylene Diphenyl Diisocyanate-Glutathione Conj

Exposure to 4,4’-methylene diphenyl diisocyanate (MDI), the most used monomeric diisocyanate, can lead to the development of occupational asthma (OA). However, the detailed molecular pathophysiological mechanisms behind how MDI exposure leading to OA remain poorly understood. Our previous research has shown that MDI or MDI-glutathione (GSH) exposure reduces the levels of endogenous human (hsa) and murine (mmu) microRNAs (miRs), specifically miR-206-3p and miR-381-3p, which were downregulated after MDI-GSH exposure, in turn activates the calcineurin/Nuclear Factor of Activated T Cells (NFAT)/inducible nitric oxide synthase (NOS2) signaling axis and the Krüppel-Like Factor 4 (KLF4)/chemokine pathways in macrophages. Prior studies have shown the roles of circular RNAs (circRNAs) species involve in the regulation of miR expression. The circRNA hsa_circ_0008726 is induced by MDI-GSH expression and plays a role to downregulate hsa-miR-206-3p in macrophages. However, the response of MDI-GSH-induced circular RNAs in downregulating hsa-miR-381-3p is not yet known. In this study, the expression of candidate circular RNAs that bind hsa-miR-381-3p was analyzed in differentiated THP-1 macrophages treated with MDI-GSH conjugates using RT-qPCR.