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Backgrounds & Aims: Liver is classically considered as the unique source of C-reactive protein (CRP) responsible for CRP plasma level in Crohn' s disease (CD). We hypothesized that adipocytes of mesenteric adipose tissue (MAT), which is especially hypertrophied in CD, may constitute an extrahepatic source of CRP. Methods: a) CRP expression was measured in biopsy specimens of adipose tissue and intestine in 6 CD, 6 UC and 4 control patients by using real-time PCR, immunochemistry, and Western blot analysis. b) CRP plasma concentrations was measured on the morning before surgery. C) Regulation of CRP mRNA expression was investigated in vitro. Results: a) Ex vivo, CRP mRNA levels detected in MAT and subcutaneous adipose tissue in UC and control patients were 15090 times higher than those detected in the intestine. Hypertrophied MAT overexpressed the CRP gene in CD patients, with mRNA levels, respectively, 8040 (p<0.05), 1450750 (p<0.01) and 14065 times (p = 0.04) higher than those detected in MAT of UC patients, MAT of controls and subcutaneous adipose tissue of the same CD subjects. Specific expression and release of CRP by adipocytes of MAT was demonstrated by immunochemistry and ELISA, respectively. b) Mesenteric CRP mRNA concentrations were correlated with plasma CRP levels in CD (r=0.79, p<0.05). c) Only E. coli (2290350 fold, p<0.01), LPS (505 fold, p<0.01), TNF- (203 fold, p<0.01) and IL-6 (82-fold, p<0.05) were able to induce an overexpression of CRP mRNA by 3T3-L1 cells. The production of CRP mRNA in TNF- pretreated 3T3-L1 cells was enhanced synergistically by the addition of E. Coli. Conclusion: Constitutive expression of CRP in mesenteric adipocytes may be preferentially enhanced by TLR4 ligands and cytokine stimuli (TNF- and IL-6). Hypertrophied MAT, which overexpress the CRP gene may be responsible, at least in part, for elevated CRP plasma levels observed in patients with active CD.
Schreiber et al. (Thu,) studied this question.