Carbon monoxide (CO) is an anti-inflammatory gaseous molecule produced endogenously by heme oxygenases (HOs) HO-1 and HO-2. However, the mechanisms underlying the anti-inflammatory effects of CO in the human bronchial epithelium are still not fully understood. In this study, the cationic peptide poly-l-arginine (PLA) was utilized to induce bronchial epithelial damage and subsequent pro-inflammatory cytokine release in the human bronchial epithelial cell line 16HBE14o-. Expression of both HO-1 and HO-2 after PLA exposure was examined. The polarized secretion of two pro-inflammatory cytokines, interleukin (IL)-6 and IL-8, was determined by ELISA. The anti-inflammatory effects of CO liberated from CO-releasing molecules (CORMs) were examined by both ELISA and western blot analysis. Our results indicate that PLA exposure leads to upregulation of HO-1 expression and p65 NF-κB phosphorylation, as well as IL-6 and IL-8 release. HO-1 induction by hemin or CORMs significantly suppressed IL-6 and IL-8 release. In addition, HO-1 knockdown further increased IL-6 and IL-8 release under basal and PLA-stimulated conditions. Our results thereby demonstrate that the HO-1/CO axis exerts significant anti-inflammatory activity during bronchial epithelial damage caused by cationic protein.
Keywords: Anti-inflammation; Bronchial epithelium; Carbon monoxide; Heme oxygenase; Poly-l-arginine.
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