title: Evidence for aberrant regulation of MAP kinase signal transduction pathway in peripheral blood mononuclear cells in patients with active celiac disease.
abstract: BACKGROUND
  Aberrant signaling via the p21/mitogen-activated proteins (MAP) kinase pathway has been described in lymphocytes of patients with various autoimmune diseases. There is little published data about the intracellular mediators and signals that regulate expression and activity of transcription factors and their effect on celiac disease induction and progression.
  
  
  OBJECTIVE
  To investigate the possible involvement of MAP kinase pathway in peripheral blood mononuclear cells (PBMC) in celiac disease and its correlation with disease activity.
  
  
  METHODS
  Expression of the total and activated forms of two MAP kinases [extracellular response kinase (ERK) and c-Jun amino terminal kinase (JNK)] were studied by Western blots in PBMC of 17 untreated and 19 treated celiac patients, and 17 controls. Seven of these untreated celiac patients were studies before and after 6 months of gluten-free diet.
  
  
  RESULTS
  Phosphorylated ERK of active celiac disease patients was significantly lower compared with controls (P < 0.01) and was increased towards normal after 6 month of gluten-free diet (P < 0.01). Phosphorylated JNK was increased significantly in the untreated celiac group (P < 0.01) and normalized towards the control level after 6 months of gluten-free diet (P < 0.04).
  
  
  CONCLUSIONS
  Aberrant MAP-kinase pathway activity is associated with active celiac disease (CD). Further studies should examine the potential role of this aberration in pathogenesis of CD.
authors.affiliation: Institute of Gastroenterology and Liver Diseases, Assaf Harofeh Medical Center Affiliated to Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. efibroide@yahoo.com
authors.forename: E
authors.initials: E
authors.lastname: Broide
authors.forename: E
authors.initials: E
authors.lastname: Scapa
authors.forename: O
authors.initials: O
authors.lastname: Bloch
authors.forename: M
authors.initials: M
authors.lastname: Shapiro
authors.forename: N A
authors.initials: NA
authors.lastname: Kimchi
authors.forename: G
authors.initials: G
authors.lastname: Ben-Yehudah
authors.forename: M J
authors.initials: MJ
authors.lastname: Rapoport
mesh_terms: D000293:Adolescent; D000328:Adult; D002446:Celiac Disease / Q000378:metabolism*; D002648:Child; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D055815:Young Adult
chemical_list: D020928:Mitogen-Activated Protein Kinases
references.citation: N Engl J Med. 2002 Jan 17;346(3):180-8
references.pmid: 11796853
references.citation: Cell Mol Immunol. 2005 Feb;2(1):20-7
references.pmid: 16212907
references.citation: J Immunol. 1989 May 1;142(9):3006-12
references.pmid: 2523422
references.citation: Lupus. 1999;8(1):24-8
references.pmid: 10025596
references.citation: J Immunol. 2003 Mar 1;170(5):2427-34
references.pmid: 12594266
references.citation: Gastroenterology. 2002 Jan;122(1):7-14
references.pmid: 11781274
references.citation: J Immunol. 2005 Nov 15;175(10):7038-45
references.pmid: 16272365
references.citation: Immunol Invest. 1989 Jan-May;18(1-4):499-508
references.pmid: 2659519
references.citation: Annu Rev Immunol. 2002;20:55-72
references.pmid: 11861597
references.citation: FEBS J. 2007 May;274(9):2376-84
references.pmid: 17403042
references.citation: Nat Med. 2001 Aug;7(8):899-905
references.pmid: 11479621
references.citation: Gut. 1990 May;31(5):497-9
references.pmid: 2112501
references.citation: J Autoimmun. 2002 Aug-Sep;19(1-2):63-70
references.pmid: 12367560
references.citation: Biochem Pharmacol. 2002 Sep;64(5-6):789-95
references.pmid: 12213571
references.citation: Autoimmunity. 1999;29(2):147-54
references.pmid: 10433077
references.citation: J Exp Med. 1993 Apr 1;177(4):1221-6
references.pmid: 8459217
references.citation: J Exp Med. 1997 Sep 15;186(6):887-97
references.pmid: 9294143
references.citation: Immunol Today. 1995 Mar;16(3):159-64
references.pmid: 7718090
references.citation: Free Radic Biol Med. 2000 May 1;28(9):1328-37
references.pmid: 10924852
references.citation: Nature. 1990 Nov 8;348(6297):125-32
references.pmid: 2122258
references.citation: Clin Immunol. 2006 May;119(2):146-55
references.pmid: 16503419
references.citation: Gastroenterology. 2005 Apr;128(4 Suppl 1):S25-32
references.pmid: 15825123
references.citation: Annu Rev Immunol. 1991;9:243-69
references.pmid: 1910678
references.citation: J Immunol. 1996 Nov 15;157(10):4721-5
references.pmid: 8906854
references.citation: J Rheumatol Suppl. 1987 Jun;14 Suppl 13:166-76
references.pmid: 3497269
references.citation: J Immunol. 2002 May 15;168(10):5342-51
references.pmid: 11994493
references.citation: Diabetologia. 1994 Dec;37(12):1195-201
references.pmid: 7895948
references.citation: J Allergy Clin Immunol. 2002 Feb;109(2):349-56
references.pmid: 11842308
references.citation: Gastroenterology. 2005 Apr;128(4 Suppl 1):S19-24
references.pmid: 15825122
references.citation: Lancet. 2003 Jul 5;362(9377):30-7
references.pmid: 12853196
references.citation: Nature. 1993 Dec 16;366(6456):643-54
references.pmid: 8259209
references.citation: Scand J Gastroenterol Suppl. 1985;114:45-54
references.pmid: 3937222
references.citation: Eur J Hum Genet. 2001 Dec;9(12):938-44
references.pmid: 11840196
references.citation: Immunology. 2001 Aug;103(4):435-40
references.pmid: 11529933
references.citation: Ann N Y Acad Sci. 2002 Nov;973:349-58
references.pmid: 12485892