HSPA12B Attenuates Acute Lung Injury During Endotoxemia in Mice
Acute lung injury (ALI) is a critical manifestation of sepsis/septic shock. Heat shock protein A12B (HSPA12B), an endothelial cell-expressed heat shock protein, shows a negative regulation of lipopolysaccharide (LPS)-induced inflammation in myocardium and endothelial cells. However, it is unclear whether HSPA12B exerts protective effects against ALI during sepsis/septic shock. In this study, we treated HSPA12B transgenic mice (Tg) and wild type littermates (WT) with LPS for 6 h to induce endotoxemia. LPS treatment significantly caused pulmonary injuries as evidenced by microarchitecture destruction, vascular leakage and neutrophil recruitment in lungs of WT mice. However, the LPS-induced pulmonary injuries were significantly attenuated in Tg mice. Moreover, the LPS-induced activation of extracellular signal-regulated kinases (ERKs) and upregulation of intercellular adhesion molecule-1 (ICAM-1) and Cyclooxygenase-2 (Cox-2) were inhibited in Tg lungs compared with that in WT mice. Additionally, Tg lungs showed a significant lower level of vascular endothelial growth factor (VEGF) compared with WT mice. Our results demonstrate a pulmonary protective effect of HSPA12B against endotoxin challenge, which indicates management of HSPA12B expression could serve as a potential therapeutic target for ALI during sepsis/septic shock.
Zhang, Xiaojin; Li, Jingjin; Li, Chuanfu; Li, Yuehua; Zhu, Weina; Zhou, Hongmei; Ding, Zhengnian; and Liu, Li. 2015. HSPA12B Attenuates Acute Lung Injury During Endotoxemia in Mice. International Immunopharmacology. Vol.29(2). 599-606. https://doi.org/10.1016/j.intimp.2015.09.022 PMID: 26428851 ISSN: 1567-5769