title: Up-regulation of growth factor independence 1 in endotoxin tolerant macrophages with low secretion of TNF-alpha and IL-6.
abstract: OBJECTIVE
  Endotoxin tolerance refers to a low response to lipopolysaccharide (LPS). We hypothesized that growth factor independence 1 (Gfi1) involves in the endotoxin tolerance in macrophages.
  
  
  METHODS
  Endotoxin tolerance was induced in the RAW264.7 cell line and thioglycolate-elicited murine peritoneal macrophages by incubation with 100 ng/ml LPS for 20 h. Macrophages without the pretreatment were set as control. Both endotoxin tolerant and control cells were then stimulated with 1,000 ng/ml LPS for indicated period of incubation. Gfi1 mRNA expression and protein production were investigated by real-time PCR and Western blotting, respectively. ELISA was performed to quantify the secretion of TNF-alpha and IL-6.
  
  
  RESULTS
  Compared with non-endotoxin tolerant macrophages, endotoxin tolerant cells secreted a lower amount of TNF-alpha and IL-6. The mRNA expression of Gfi1 in endotoxin tolerant macrophages was higher than that of control in both RAW264.7 cells and thioglycolate-elicited murine peritoneal macrophages. The protein production was accordingly up-regulated in endotoxin tolerant RAW264.7 cells.
  
  
  CONCLUSIONS
  In in vitro endotoxin tolerant macrophages, the expression of Gfi1 mRNA and protein were up-regulated after high dose LPS stimulation, accompanied with a blunted TNF-alpha and IL-6 secretion. Gfi1 might participate in the mechanism of endotoxin tolerance.
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Min-Fang
authors.initials: MF
authors.lastname: Zhu
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Jie-Ming
authors.initials: JM
authors.lastname: Qu
authors.forename: Hui-Jun
authors.initials: HJ
authors.lastname: Zhang
authors.forename: Shuang-Cheng
authors.initials: SC
authors.lastname: Zhou
authors.forename: Sheng-Fu
authors.initials: SF
authors.lastname: Dong
authors.forename: Hong-Ni
authors.initials: HN
authors.lastname: Jiang
authors.forename: Hanssa
authors.initials: H
authors.lastname: Summah
mesh_terms: D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; C079873:Gfi1 protein, mouse; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha
references.citation: Nature. 2007 Jun 21;447(7147):972-8
references.pmid: 17538624
references.citation: Eur J Immunol. 2006 Feb;36(2):421-30
references.pmid: 16402406
references.citation: Cell Microbiol. 2006 Jul;8(7):1096-105
references.pmid: 16819963
references.citation: Scand J Immunol. 2003 Dec;58(6):613-9
references.pmid: 14636417
references.citation: J Trauma. 1994 Jul;37(1):82-9; discussion 89-90
references.pmid: 8028064
references.citation: Infect Immun. 1996 Mar;64(3):1011-5
references.pmid: 8641750
references.citation: Trends Immunol. 2009 Oct;30(10):475-87
references.pmid: 19781994
references.citation: Crit Care Med. 2002 Jan;30(1 Supp):S64-S73
references.pmid: 11891406
references.citation: J Clin Immunol. 1992 Nov;12(6):440-50
references.pmid: 1287036
references.citation: N Engl J Med. 2000 Aug 3;343(5):338-44
references.pmid: 10922424
references.citation: J Biol Chem. 2007 Sep 14;282(37):26857-26864
references.pmid: 17646159
references.citation: Am J Respir Cell Mol Biol. 2000 Aug;23(2):128-32
references.pmid: 10919975
references.citation: J Leukoc Biol. 1997 Jan;61(1):88-95
references.pmid: 9000541
references.citation: J Surg Res. 1994 Jul;57(1):85-92
references.pmid: 8041155
references.citation: Nat Genet. 2002 Mar;30(3):295-300
references.pmid: 11810106
references.citation: J Clin Invest. 1993 Oct;92(4):2053-9
references.pmid: 7691891
references.citation: J Appl Physiol (1985). 1992 Sep;73(3):1008-13
references.pmid: 1400011
references.citation: Crit Care. 2006;10(5):233
references.pmid: 17044947
references.citation: Shock. 1995 Apr;3(4):252-8
references.pmid: 7600192
references.citation: Biochim Biophys Acta. 1999 Jun 8;1450(2):130-44
references.pmid: 10354505