Identification of genes upregulated in the inflamed colonic lesions of Crohn's disease.
To identify the molecular mechanism which primarily plays a role in the pathogenesis of Crohn's disease (CD) without prior hypothesis, differential display method was employed to detect differentially expressed genes between the inflamed and uninflamed colonic samples from one patient with CD. The mRNA levels of these genes were subsequently semi-quantitated in affected and unaffected tissues from six patients using reverse transcriptase polymerase chain reaction (RT-PCR). Six genes including long form FLICE inhibitory protein (FLIP(L)) were found to be consistently overexpressed in the inflamed colonic CD tissues. Immunohistochemical studies revealed that FLIP(L) expressing cells were lamina propria lymphocytes (LPLs). The present study suggested that overexpression of FLIP(L) in the LPLs may be involved in the pathogenesis of CD through defective activation-induced cell death. In addition, this study provided evidence for a possible role of several previously unsuspected genes in the pathogenesis of CD.
Hagiwara
K
K
Department of Allergy and Rheumatology, University of Tokyo, Tokyo, 113-0033, Japan.
Yamaguchi
A
A
Tsuchiya
N
N
Kitamura
S
S
Iwadare
J
J
Sahara
R
R
Yamamoto
K
K
Tokunaga
K
K
D000328:Adult; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D003424:Crohn Disease / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D000081410:Germinal Center Kinases; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000235:genetics*
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; D000081410:Germinal Center Kinases; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; D017346:Protein Serine-Threonine Kinases; D010749:Phosphoprotein Phosphatases; C106079:protein phosphatase 6; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases