Toll-like receptor-4-interacting surfactant protein-A-derived peptide reduces inflammation in a mouse model of intratracheal lipopolysaccharide challenge.

Abstract

Abstract Acute lung injury is characterized by inflammation and respiratory failure. In this work, we evaluated the effect of Toll-like receptor 4 (TLR4)-interacting SPA4 peptide on inflammatory and physiological parameters in cells and in mice against lipopolysaccharide (LPS). Cellular toxicity was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Binding of SPA4 peptide was studied in cells transiently transfected with a plasmid DNA encoding TLR4. We assessed the changes in the levels of cytokines and chemokines in supernatants of cells treated with SPA4 peptide simultaneously or post-LPS challenge. The extent of lung edema, levels of cytokines and chemokines, and changes in lung histopathology, blood gas and electrolytes, and serum lactate levels, were then determined after SPA4 peptide treatment in a mouse model of acute lung inflammation and injury induced by intratracheal LPS challenge. Our results demonstrate that the SPA4 peptide is not toxic, and binds to TLR4 at the cellular level. A significant reduction was observed in secreted levels of LPS-induced cytokines and chemokines in cell-free supernatants. Correspondingly, the levels of TNF-α, IL-1β, IL-6, MIP-2, KC, and MCP-1 were reduced in bronchoalveolar lavage fluids of SPA4 peptide-treated mice. Moreover, SPA4 peptide treatment attenuated the LPS-induced pulmonary inflammation, lung edema, serum lactate, and blood gas and electrolyte parameters. Together, our results suggest that the SPA4 peptide treatment can help control lung inflammation and injury.