부산대학교 도서관

Prior research demonstrated that glucagon has protective roles against inflammation, but its effect on the resolution of inflammation remains elusive. Using in vitro and in vivo approaches, this study aimed to investigate the pro-resolving p otential of glucagon on pulmonary neutrophilic inflammation caused by lipopolysaccharide. Lipopolysaccharide induced an increase in the proportions of neutrophils positives to glucagon receptor (GcgR) in vitro. In addition, lipopolysaccharide induced an increase in the ne utrophil accumulation and expression of GcgR by the inflammatory cells in the lungs, however, without altering glucagon levels. Intranasal treatment with glu cagon, at the peak of neutrophilic inflammation, reduced the neutrophil number in the bronchoalveolar lavage (BAL), and lung tissue within 24 h. The reduction of neutrophil ic inflammation provoked by glucagon was accompanied by neutrophilia in the blood, an in crease in the apoptosis rate of neutrophils in the BAL, enhance in the pro-apoptotic Ba x protein expression, and decrease in the anti-apoptotic Bcl-2 protein levels in the lung. Glucagon also induced a rise in the cleavage of caspase-3 in the lungs; however, it was not significant. Glucagon inhibited the levels of IL-1β and TNF-α while increasing the content of pro-resolving mediators transforming growth factor (TGF-β1) and PGE2 in the BAL and lung. Finally, glucagon inhibited lipopolysaccharide-induced airway hyper-reactivity, as evidenced by the reduction in lung elastance values in response to methac holine. In conclusion, glucagon-induced resolution of neutrophilic inflammation by promoting cessation of neutrophil migration and a rise of neutrophil apoptosis and the levels of pro-resolving mediators TGF-β1 and PGE2. [ABSTRACT FROM AUTHOR]