Heme oxygenase-1 upregulation significantly inhibits TNF-alpha and Hmgb1 releasing and attenuates lipopolysaccharide-induced acute lung injury in mice.
The present study was designed to investigate whether administration of CoPPIX, an HO-1 inducer, could significantly inhibit TNF-alpha and Hmgb1 expression and thus attenuate the acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice. Acute lung injury was induced successfully by intratracheal administration of LPS (0.5 mg/kg) in male BALB/c mice. CoPPIX or ZnPPIX (an HO-1 inhibitor) was administered to mice 24 h prior to LPS exposure. It was found that CoPPIX (5, 10 mg/kg, i.p.) caused a significant reduction in the total cells and neutrophils in BALF, a significant reduction in the W/D ratio and EBA leakage at 24 h after LPS challenge. Furthermore, the histopathologic findings indicated that alveolitis with leukocyte infiltration in the alveolar space was less severe in the CoPPIX-treated mice than in the mice treated with LPS alone. In addition, CoPPIX was also believed to have down-regulated the expression of LPS-induced proinflammatory cytokines, including early proinflammatory cytokine TNF-a, and late proinflammatory cytokine Hmgb1. In contrast, no obvious difference was observed between the ZnPPIX group and the LPS group. These findings demonstrate the significant protection of CoPPIX against LPS-induced ALI, and the effect mechanism of CoPPIX was associated with decreasing the expression of TNF-a and Hmgb1.
Gong
Quan
Q
Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
Yin
Hui
H
Fang
Min
M
Xiang
Ying
Y
Yuan
Chun-Lei
CL
Zheng
Guo-Ying
GY
Yang
Heng
H
Xiong
Ping
P
Chen
Gang
G
Gong
Fei-Li
FL
Zheng
Fang
F
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D024243:HMGB1 Protein / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D008070:Lipopolysaccharides; D008168:Lung / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011524:Protoporphyrins / Q000008:administration & dosage / Q000494:pharmacology*; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation
D024243:HMGB1 Protein; D008070:Lipopolysaccharides; D011524:Protoporphyrins; D014409:Tumor Necrosis Factor-alpha; C007095:cobaltiprotoporphyrin; D051547:Heme Oxygenase-1