title: Different effect of glutamine on macrophage tumor necrosis factor-alpha release and heat shock protein 72 expression in vitro and in vivo.
abstract: Macrophage plays a vital role in sepsis. However, the modulatory effect of glutamine (Gln) on macrophage/ monocyte-mediate cytokines release is still controversial. Thus, we investigated the effect of Gln on macrophage tumor necrosis factor (TNF)-alpha release and heat shock protein (HSP) 72 expression in vivo and in vitro. Data from our study indicated that the increase of HSP72 expression was significant at 8 mM of Gln 4 h after lipopolysaccharide (LPS) stimulation and became independent of Gln concentrations at 24 h, whereas TNF-alpha release was dose- and time-dependent on Gln. Heat stress (HS) induced more HSP72 and less TNF-alpha production compared with the non-HS group. However, the production of TNF-alpha in cells pretreated with HS was increased with increasing concentrations of Gln. Treatment with various concentrations of Gln for 1 h and then 0.5 mM Gln for 4 h led to an increase in HSP72 expression, but not in TNF-alpha production. In sepsis model mice, Gln treatment led to a significantly lower intracellular TNF-alphalevel and an increase in HSP72 expression in mouse peritoneal macrophages. Our results demonstrate that Gln directly increases TNF-alpha release of LPS-stimulated RAW264.7 macrophages in a dose-dependent manner, and also decreases mouse peritoneal macrophages TNF-a release in the sepsis model. Taken together, our data suggest that there may be more additional pathways by which Gln modulates cytokine production besides HSP72 expression in macrophage during sepsis.
authors.affiliation: Department of Anesthesiology/Intensive Care Unit, 6th Municipal Hospital, Medical College of Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Mengfan
authors.initials: M
authors.lastname: Liang
authors.forename: Xuemin
authors.initials: X
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.forename: Quanhong
authors.initials: Q
authors.lastname: Zhou
authors.forename: Chuanyao
authors.initials: C
authors.lastname: Tong
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
mesh_terms: D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005973:Glutamine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism*; D018869:Heat-Shock Response; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D018805:Sepsis / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D050884:HSP72 Heat-Shock Proteins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D005973:Glutamine