Evidence for aberrant regulation of MAP kinase signal transduction pathway in peripheral blood mononuclear cells in patients with active celiac disease.
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.
Broide
E
E
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
Scapa
E
E
Bloch
O
O
Shapiro
M
M
Kimchi
N A
NA
Ben-Yehudah
G
G
Rapoport
M J
MJ
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
D020928:Mitogen-Activated Protein Kinases
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