Inhaled [D-Ala < sup > 2 < /sup > ]-Dynorphin 1-6 Prevents Hyperacetylation and Release of High Mobility Group Box 1 in a Mouse Model of Acute Lung Injury

In this study, we demonstrate that inhaled [D-Ala2]-dynorphin 1-6 (leytragin), a peptide agonist of δ-opioid receptors, significantly inhibits HMGB1 secretion in mice with lipopolysaccharide- (LPS-) induced acute lung injury. The mechanism of action involves preventing HMGB1's hyperacetylation at critical lysine residues within nuclear localization sites, as well as promoting the expression of sirtuin 1 (SIRT1), an enzyme known to deacetylate HMGB1. Leytragin's effects are mediated by opioid receptors, since naloxone, an antagonist of opioid receptors, abrogates the leytragin effect on SIRT1 expression. Overall, our results identify leytragin as a promising therapeutic agent for the treatment of pulmonary inflammation associated with HMGB1 release. In a broader context, we demonstrate that the opioidergic system in the lungs may represent a promising target for the treatment of inflammatory lung diseases.PMID:34616852 | PMC:PMC8490075 | DOI:10.1155/2021/4414544

Source: Journal of Immunology Research - October 7, 2021 Category: Allergy & Immunology Authors: Vladislav N Karkischenko Veronika I Skvortsova Melik T Gasanov Yuriy V Fokin Maxim S Nesterov Nataliya V Petrova Oxana V Alimkina Igor A Pomytkin Source Type: research