title: Heme oxygenase-1 ameliorates LPS-induced acute lung injury correlated with downregulation of interleukin-33.
abstract: Although studies have shown that heme oxygenase-1 (HO-1) can abrogate leukocyte recruitment and tissue injury after LPS stimulation, the underlying mechanisms remain incompletely understood. Interleukin (IL)-33, a new member of the IL-1 family, is found to play a crucial immunoregulatory effect on the MD2/TLR4 complex expression. Moreover, TLR4 further promotes the activation of NF-κB and the production of proinflammatory mediators, which exacerbate neutrophil infiltration and organ damage. The present study was designed to determine whether the protection of HO-1 against LPS-induced acute lung injury (ALI) is involved in downregulation of IL-33. We observed that the levels of IL-33 mRNA and protein in LPS-stimulated macrophages were strongly suppressed by a potent HO-1 inducer, CoPP, treatment. Meanwhile, CoPP significantly reduced the expression of TLR4 and TNF-α in IL-33-pretreated macrophages followed LPS challenge. In the murine model of LPS-induced ALI, CoPP treatment resulted in a remarkable decrease in LPS-mediated leukocyte exudation, Evans blue dye albumin (EBA) leakage as well as histopathologic disruption. Notably, CoPP treatment markedly inhibited the expression of IL-33 and TLR4 in lung tissues under LPS stimulation. Therefore, these data suggest that the cytoprotection of HO-1 in LPS-induced pulmonary injury is associated with negative regulation of IL-33 and TLR4-mediated inflammatory response.
authors.affiliation: Department of Microbiology and Immunology, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yin
authors.forename: Xiangyong
authors.initials: X
authors.lastname: Li
authors.forename: Baohong
authors.initials: B
authors.lastname: Yuan
authors.forename: Bobin
authors.initials: B
authors.lastname: Zhang
authors.forename: Shilian
authors.initials: S
authors.lastname: Hu
authors.forename: Hongbiao
authors.initials: H
authors.lastname: Gu
authors.forename: Xiaobao
authors.initials: X
authors.lastname: Jin
authors.forename: Jiayong
authors.initials: J
authors.lastname: Zhu
mesh_terms: D055371:Acute Lung Injury / Q000276:immunology* / Q000473:pathology; D000818:Animals; D015536:Down-Regulation; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D000067596:Interleukin-33; D007378:Interleukins / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000819:agonists / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000187:drug effects; D011719:Pyrazines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D011719:Pyrazines; D011758:Pyrroles; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C484301:cyclohexyl-octahydro-pyrrolo(1,2-a)pyrazine; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse