Blockade of Cluster of Differentiation 38 Alleviates Sepsis-Induced Acute Lung Injury in Mice Through Inflammation Suppression via Regulating Toll-Like Receptor 4/Nuclear Factor kappa B p65

Abstract

This study aimed to investigate the role of CD38 inhibition in sepsis-induced acute lung injury (ALI) using a murine model. ALI, commonly associated with excessive inflammation, was induced by cecal ligation and puncture (CLP). We observed an increase in CD38 expression in lung tissue over time in the ALI mice. To address this, we administered the CD38 inhibitor, 78C, subcutaneously at a dose of 10 mg/kg. Following treatment, we assessed lung function, inflammatory cell levels, and cytokine concentrations in bronchoalveolar lavage fluid. We also examined the activity of the TLR4/NF-κB p65 signaling pathway in lung tissue. Results showed that 78C treatment improved lung function and reduced inflammatory cells and cytokines in ALI mice. Moreover, 78C inhibited the expression of the TLR4/NF-κB p65 signaling pathway in lung tissue. This CD38 blockade effectively mitigated inflammation levels in lung tissue, ameliorated lung function, and alleviated sepsis-induced ALI induced by CLP. These findings suggest that targeting CD38 to modulate the TLR4/NF-κB p65 inflammatory pathway holds promise as a therapeutic strategy for sepsis-induced ALI.