title: Caveolin-1 scaffolding domain peptides enhance anti-inflammatory effect of heme oxygenase-1 through interrupting its interact with caveolin-1.
abstract: Caveolin-1(Cav-1) scaffolding domain (CSD) peptides compete with the plasma membrane Cav-1, inhibit the interaction of the proteins and Cav-1, and re-store the functions of Cav-1 binding proteins. Heme oxygenase-1 (HO-1) binds to Cav-1 and its enzymatic activity was inhibited. In this study, we investigated the effect of CSD peptides on interaction between HO-1 and Cav-1, and on the HO-1 activity in vitro and in vivo. Our data showed that CSD peptides decreased the compartmentalization of HO-1 and Cav-1, and increased the HO-1 activity both in LPS-treated alveolar macrophages and in mice. Meanwhile, CSD peptides obviously ameliorated the pathology changes in mice and lowered the following injury indexes: the wet/dry ratio of lung tissues, total cell numbers in bronchoalveolar lavage fluid and lactate dehydrogenase activity in the serum. Mechanistically, it was firstly found that CSD peptides promoted alveolar macrophages polarization to M2 phenotype and inhibited the IκB degeneration. Furthermore, CSD peptides down-regulated the expression of IL-1β, IL-6, TNF-α, MCP-1, and iNOS in alveolar macrophages and in lung tissue. However, the protective role of CSD peptides on LPS-induced acute lung injury in mice could be abolished by zinc protoporphyrin IX (ZnPP, a HO-1 activity inhibitor). In summary, CSD peptides have beneficial anti-inflammatory effects by restoring the HO-1 activity suppressed by Cav-1 on plasma membrane.
authors.affiliation: Wuxi Medical School, Jiangnan University, Wuxi, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Weng
authors.affiliation: Wuxi Medical School, Jiangnan University, Wuxi, China.
authors.forename: Xiao-Tong
authors.initials: XT
authors.lastname: Zhang
authors.affiliation: Wuxi Medical School, Jiangnan University, Wuxi, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Sheng
authors.affiliation: Wuxi Medical School, Jiangnan University, Wuxi, China.
authors.forename: Wen-Fang
authors.initials: WF
authors.lastname: Tian
authors.affiliation: Wuxi Medical School, Jiangnan University, Wuxi, China.
authors.forename: Jun-Liang
authors.initials: JL
authors.lastname: Chen
authors.affiliation: Wuxi Medical School, Jiangnan University, Wuxi, China.
authors.forename: Jia-Jia
authors.initials: JJ
authors.lastname: Yuan
authors.affiliation: Department of Anesthesiology, the Affiliated Hospital of Jiangnan University, Wuxi, China.
authors.forename: Ji-Ru
authors.initials: JR
authors.lastname: Zhang
authors.affiliation: Wuxi Medical School, Jiangnan University, Wuxi, China.
authors.forename: Qing-Feng
authors.initials: QF
authors.lastname: Pang
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D000818:Animals; D051242:Caveolin 1 / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008262:Macrophage Activation / Q000187:drug effects; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects
chemical_list: D051242:Caveolin 1; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D020011:Protective Agents; C571371:caveolin-1 (82-101); D051547:Heme Oxygenase-1
keywords: acute lung injury; caveolin-1; caveolin-1 scaffolding domain peptide; heme oxygenase-1; lipopolysaccharide