Abstract:
:Mucosal inflammation in patients with inflammatory bowel disease (IBD) is characterized by an alteration of prohormone chromogranin A (CgA) production. The recent demonstration of an implication of CgA in collagenous colitis and immune regulation provides a potential link between CgA-derived peptides (catestatin, CTS) and gut inflammation. Colitis was induced by administration of dextran sulfate sodium or 2, 4 dinitrobenzenesulfonic acid to C57BL/6 mice. Treatment with human (h)CTS or its proximal or distal part was started one day before colitis induction and colonic inflammatory markers were determined. Pro-inflammatory cytokines were evaluated in peritoneal isolated and bone marrow derived macrophages (BMDMs); p-STAT3 level was studied. Serum levels of CgA and CTS were assessed in experimental colitis and in a separate study in IBD patients and healthy controls. We show that sera from IBD patients and that in experimental colitis conditions the colonic level of mouse (m)CgA and mCTS are significantly increased. Moreover, in vivo treatment with human (h)CTS reduces the disease onset and suppresses exacerbated inflammatory responses in preclinical settings of colitis associated with an increase of p-STAT3. In vitro, hCTS treatment decreases proinflammatory cytokine release by peritoneal macrophages and BMDMs and increases p-STAT3 levels. These results support the hypothesis that CTS is increased during colitis and that hCTS modulates intestinal inflammation via the macrophage population and through a STAT-3 dependent pathway in a murine model of colitis. Identification of the molecular mechanism underlying the protective role of this peptide may lead to a novel therapeutic option in IBD.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Rabbi MF,Labis B,Metz-Boutigue MH,Bernstein CN,Ghia JEdoi
10.1016/j.bcp.2014.03.003subject
Has Abstractpub_date
2014-06-01 00:00:00pages
386-98issue
3eissn
0006-2952issn
1873-2968pii
S0006-2952(14)00161-0journal_volume
89pub_type
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:1984-02-01 00:00:00
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pub_type: 杂志文章
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