Glutamine's protection against sepsis and lung injury is dependent on heat shock protein 70 expression

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2007-05, Vol.292 (5), p.R1839-R1845
• Main Authors: Singleton, Kristen D, Wischmeyer, Paul E
• Format: Article
• Language: English
• Subjects: Animals; Gene Expression Regulation; Glutamine - pharmacology; HSP70 Heat-Shock Proteins - genetics; HSP70 Heat-Shock Proteins - metabolism; Interleukin-6 - metabolism; Lung - metabolism; Lung Diseases - complications; Lung Diseases - prevention & control; Male; Mice; Mice, Knockout; NF-kappa B - metabolism; Sepsis - complications; Sepsis - prevention & control; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00755.2006

Department of Anesthesiology, University of Colorado Health Sciences Center, Denver, Colorado Submitted 30 October 2006 ; accepted in final form 9 January 2007 Glutamine (GLN) has been shown to protect against inflammatory injury and illness in experimental and clinical settings. The mechanism of this protection is unknown; however, laboratory and clinical trial data have indicated a relationship between GLN-mediated protection and enhanced heat shock protein 70 (HSP70) expression. The aim of this study was to examine the hypothesis that GLN's beneficial effect on survival, tissue injury, and inflammatory response after inflammatory injury is dependent on HSP70 expression. Mice with a specific deletion of the HSP70 gene underwent cecal ligation and puncture (CLP)-induced sepsis and were treated with GLN (0.75 g/kg) or a saline placebo 1 h post-CLP. Lung tissue NF- B activation, inflammatory cytokine response, and lung injury were assessed post-CLP. Survival was assessed for 5 days post-CLP. Our results indicate that GLN administration improved survival in Hsp70 +/+ mice vs. Hsp70 +/+ mice not receiving GLN; however, GLN exerted no survival benefit in Hsp70 –/– mice. This was accompanied by a significant decrease in lung injury, attenuation of NF- B activation, and proinflammatory cytokine expression in GLN-treated Hsp70 +/+ mice vs. Hsp70 +/+ mice not receiving GLN. In the Hsp70 –/– mice, GLN's attenuation of lung injury, NF- B activation, and proinflammatory cytokine expression was lost. These results confirm our hypothesis that HSP70 expression is required for GLN's effects on survival, tissue injury, and the inflammatory response after global inflammatory injury. inflammation; NF- B; Hsp70.1 and Hsp70.3 genes; cecal ligation and puncture Address for reprint requests and other correspondence: K. D. Singleton, Univ. of Colorado Health Sciences Center, Dept. of Anesthesiology, 4200 E. Ninth Ave., Campus Box B113, Denver, CO 80262 (e-mail: kristen.singleton{at}uchsc.edu )