Glutamine attenuates acute lung injury by inhibition of high mobility group box protein-1 expression during sepsis.
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.
Kwon
Woon Yong
WY
Department of Emergency Medicine, Seoul National University College of Medicine, Chongno-gu, Seoul, South Korea.
Suh
Gil Joon
GJ
Kim
Kyung Su
KS
Jo
You Hwan
YH
Lee
Jae Hyuk
JH
Kim
Kyuseok
K
Jung
Sung Koo
SK
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
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