title: Stanniocalcin-1 ameliorates lipopolysaccharide-induced pulmonary oxidative stress, inflammation, and apoptosis in mice.
abstract: Stanniocalcin-1 (STC1) is an endogenous glycoprotein whose anti-inflammatory effects occur through induction of uncoupling proteins to reduce oxidative stress. In this study, we tested the hypothesis that exogenous recombinant human STC1 (rhSTC1) protects against lipopolysaccharide (LPS)-induced acute lung injury in mice. Anesthetized C57BL/6 mice underwent intratracheal spraying of LPS (20 µg/10 g body wt), and lung injury was assessed 24h later by analyzing pulmonary edema, bronchoalveolar lavage fluid, and lung histopathology. Lung inflammation, oxidative stress, and expression of STC1 and its downstream uncoupling protein 2 (UCP2) were analyzed at specific time points. Expression of UCP2 was suppressed initially but was subsequently upregulated after STC1 elevation in response to intratracheal administration of LPS. Intratracheal rhSTC1 treatment 1h before or after LPS spraying significantly attenuated pulmonary inflammation, oxidative stress, cell apoptosis, and acute lung injury. Pretreatment with STC1 short interfering RNA 48 h before LPS spraying inhibited the expression of STC1 and UCP2 and significantly increased the extent of lung injury. These findings suggest that STC1 is an endogenous stress protein that may counteract LPS-induced lung injury by inhibiting the inflammatory cascade and inducing antioxidant and antiapoptotic mechanisms. However, the potential clinical application of STC1 and the direct linkage between UCP2 and LPS-induced lung injury remain to be further investigated.
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Shih-En
authors.initials: SE
authors.lastname: Tang
authors.affiliation: Department of Critical Care Medicine, Landseed Hospital, Taoyuan, Taiwan.
authors.forename: Chin-Pyng
authors.initials: CP
authors.lastname: Wu
authors.affiliation: Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Shu-Yu
authors.initials: SY
authors.lastname: Wu
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Chung-Kan
authors.initials: CK
authors.lastname: Peng
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Wann-Cherng
authors.initials: WC
authors.lastname: Perng
authors.affiliation: Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Bor-Hwang
authors.initials: BH
authors.lastname: Kang
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan. Electronic address: d1204812@ndmctsgh.edu.tw.
authors.forename: Shi-Jye
authors.initials: SJ
authors.lastname: Chu
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan; Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei 114, Taiwan. Electronic address: kun@ndmctsgh.edu.tw.
authors.forename: Kun-Lun
authors.initials: KL
authors.lastname: Huang
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D007473:Ion Channels / Q000235:genetics* / Q000378:metabolism; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage*; D000071246:Uncoupling Protein 2
chemical_list: D006023:Glycoproteins; D007473:Ion Channels; D008070:Lipopolysaccharides; D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C000604389:UCP2 protein, human; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; C051795:teleocalcin
keywords: Acute lung injury; Free radicals; Lipopolysaccharide; Oxidative stress; Stanniocalcin-1; Stress proteins; Uncoupling protein 2