PHLDA1 Promotes Lung Contusion by Regulating the Toll-Like Receptor 2 Signaling Pathway.

BACKGROUND/AIMS:Lung contusion is a potentially lethal injury. Pleckstrin homology-like domain family A, member-1 (PHLDA1) is known to play crucial roles in cell proliferation and apoptosis. In this study, we investigated the biological role of PHLDA1 in lung contusion. METHODS:The expression levels of PHLDA1 and TLR2 were detected by real time PCR and western. The cytokines were determined by ELISA. The inflammatory factors were detected by flow cytometry. The lung injury was determined by HE staining. RESULTS:PHLDA1 gene and protein expression levels were up-regulated in a mouse lung-contusion model, together with increased neutrophil and macrophage contents. Down-regulation of PHLDA1 by interfering RNA (siPHLDA1 mice) decreased lung injury and neutrophil infiltration. Inflammatory factors, including interleukin (IL)-1β, IL-6, mouse homolog of human growth-regulated oncogene-α (KC), tumor necrosis factor-α, CC chemokine ligand (CCL) 2, and CCL12 were also decreased in siPHLDA1 mice. Expression levels of Toll-like receptor 2 (TLR2) were increased in the lung-contusion mouse model, but were decreased when PHLDA1 was down-regulated. CONCLUSION:These results demonstrate that PHLDA1 plays a critical role in the development of progressive lung contusion and subsequent inflammation. This information furthers our understanding of the pathogenesis of lung contusion, and suggests that PHLDA1 blockade may represent a potential therapeutic strategy for the treatment of this injury.

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