title: Glutamine attenuates acute lung injury by inhibition of high mobility group box protein-1 expression during sepsis.
abstract: Heat shock protein 70 (HSP70) is reported as the main factor responsible for the beneficial effects of glutamine (GLN) and as a negative regulator of high mobility group box protein-1 (HMGB-1) expression. Our aim was to determine whether GLN attenuates acute lung injury (ALI) by the inhibition of HMGB-1 expression during sepsis. Male Sprague-Dawley rats were subjected to caecal ligation and puncture (CLP) to induce sepsis. GLN or saline was administered through tail vein 1 h after CLP. Then, quercetin (Q), an inhibitor of HSP70, was utilised to assess the role of the enhanced HSP70. We observed the survival of the subjects. At 24 h post-CLP, we measured lung HSP70, phosphorylated heat shock factor-1 (HSF-1-p) and HMGB-1 expressions, NF-kappaB DNA-binding activity and ALI occurrence. We also measured serum HSP70, IL-6 and HMGB-1 concentrations. GLN improved survival during sepsis. In GLN-treated rats, lung HSP70 and HSF-1-p expressions were enhanced, lung HMGB-1 expression and NF-kappaB DNA-binding activity were suppressed, and ALI was attenuated. Furthermore, in GLN-administered rats, serum HSP70 concentration was higher, and serum IL-6 and HMGB-1 concentrations were lower than those in non-treated rats. Q inhibited the enhancement of HSP70 and HSF-1-p expressions and abrogated the GLN-mediated benefits. In conclusion, GLN attenuated ALI and improved survival by the inhibition of HMGB-1 expression during sepsis in rats. These benefits were associated with the enhancement of HSP70 expression by GLN.
authors.affiliation: Department of Emergency Medicine, Seoul National University College of Medicine, Chongno-gu, Seoul, South Korea.
authors.forename: Woon Yong
authors.initials: WY
authors.lastname: Kwon
authors.forename: Gil Joon
authors.initials: GJ
authors.lastname: Suh
authors.forename: Kyung Su
authors.initials: KS
authors.lastname: Kim
authors.forename: You Hwan
authors.initials: YH
authors.lastname: Jo
authors.forename: Jae Hyuk
authors.initials: JH
authors.lastname: Lee
authors.forename: Kyuseok
authors.initials: K
authors.lastname: Kim
authors.forename: Sung Koo
authors.initials: SK
authors.lastname: Jung
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002432:Cecum; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis / Q000737:chemistry; D005973:Glutamine / Q000008:administration & dosage*; D024243:HMGB1 Protein / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000097:blood; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis / Q000097:blood / Q000502:physiology; D000076249:Heat Shock Transcription Factors; D015850:Interleukin-6 / Q000097:blood; D008168:Lung / Q000737:chemistry; D008171:Lung Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011677:Punctures; D011794:Quercetin / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000150:complications / Q000378:metabolism*; D014157:Transcription Factors / Q000032:analysis / Q000737:chemistry
chemical_list: D004268:DNA-Binding Proteins; D024243:HMGB1 Protein; D018840:HSP70 Heat-Shock Proteins; C104200:Hbp1 protein, rat; D000076249:Heat Shock Transcription Factors; D015850:Interleukin-6; D016328:NF-kappa B; D014157:Transcription Factors; D005973:Glutamine; D004247:DNA; D011794:Quercetin