title: Role of Metallothionein in Post-Burn Inflammation.
abstract: Metallothioneins (MTs) are a family of low molecular-weight and cysteine-rich metalloproteins that regulate metal metabolism and protect cells from oxygen free radicals. Recent studies suggested that MTs have some anti-inflammatory effects. However, the role of MTs in post-burn inflammation remains unclear. This study is designed to investigate the role of MTs in post-burn inflammation in a mouse burn model. MT-I/II null (-/-) and C57BL/6 wild-type (WT) mice were randomly divided into sham burn, burn, Zn treated, and Zn-MT-2 treated groups. The inflammatory cytokines levels were measured by enzyme-linked immunosorbent assay (ELISA). Myeloperoxidase (MPO) activity was determined by spectrophotometry. In in vitro study, exogenous MT-2 was added to macrophages that were stimulated with burn serum in the presence or absence of a p38 MAPK inhibitor SB203580. The IL-6 and TNF-α messenger RNA (mRNA) expression were detected by quantitative real-time polymerase chain reaction. The levels of p38 expression were determined by Western blot. Burn induced increased inflammatory cytokines such as interleukin (IL)-1β, IL-6, tumor necrosis factors-α, and macrophage chemoattractant protein-1 production in burn wound and serum. The MPO activities in the lung and heart were also increased after burn. These effects were significantly more prominent in MT (-/-) mice than in WT mice. Furthermore, these effects were inhibited by administration of exogenous MT-2 to both WT and MT (-/-) mice. Exogenous MT-2 inhibited the p38 expression and abrogated the increase of IL-6 and TNF-α mRNA expression from macrophages that were stimulated with burn serum. The effect of MT-2 was not further strengthened in the presence of SB203580. MTs may have a protective role against post-burn inflammation and inflammatory organ damage, at least partly through inhibiting the p38 MAPK signaling.
authors.affiliation: Burn and Plastic Surgery Department, The First Affiliated Hospital of Chengdu Medical College, 278 Baoguang Road, Xindu District, Chengdu, 610500, Sichuan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Basic Medical College of Chengdu Medical College, Sichuan, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Burn and Plastic Surgery Department, The First Affiliated Hospital of Chengdu Medical College, 278 Baoguang Road, Xindu District, Chengdu, 610500, Sichuan, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Liu
authors.affiliation: Burn and Plastic Surgery Department, The First Affiliated Hospital of Chengdu Medical College, 278 Baoguang Road, Xindu District, Chengdu, 610500, Sichuan, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Xu
authors.affiliation: Burn and Plastic Surgery Department, The First Affiliated Hospital of Chengdu Medical College, 278 Baoguang Road, Xindu District, Chengdu, 610500, Sichuan, China.
authors.forename: Xuelian
authors.initials: X
authors.lastname: Chen
authors.affiliation: Burn and Plastic Surgery Department, The First Affiliated Hospital of Chengdu Medical College, 278 Baoguang Road, Xindu District, Chengdu, 610500, Sichuan, China.
authors.forename: Hairong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Burn and Plastic Surgery Department, The First Affiliated Hospital of Chengdu Medical College, 278 Baoguang Road, Xindu District, Chengdu, 610500, Sichuan, China. liuyueming618@126.com.
authors.forename: Yueming
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D002056:Burns / Q000473:pathology*; D018932:Chemokine CCL2 / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007093:Imidazoles / Q000494:pharmacology; D007249:Inflammation / Q000473:pathology*; D053583:Interleukin-1beta / Q000097:blood / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009195:Peroxidase / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C587672:IL1B protein, mouse; D007093:Imidazoles; D053583:Interleukin-1beta; D015850:Interleukin-6; D011725:Pyridines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D008668:Metallothionein; D009195:Peroxidase; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580
keywords: burn; inflammation; metallothionein; p38
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