Ghrelin ameliorates colonic inflammation. Role of nitric oxide and sensory nerves.

• Autorzy: Konturek P.C. , Brzozowski T. , Engel M. , Burnat G. , Gaca P. , Kwiecien S. , Pajdo R. , Konturek S.J.
• Języki publikacji: EN

Abstrakty

EN

Ghrelin is a novel growth hormone (GH)-releasing and orexigenic peptide with anti-inflammatory activities. However, the role of ghrelin in the colonic inflammation is still controversial. The aim of the present study was: 1) to examine the expression of ghrelin and TNF- mRNA in the inflamed colonic mucosa of patients with ulcerative colitis (UC), 2) to analyze the effect of treatment with exogenous ghrelin on the healing of trinitrobenze sulphonic acid (TNBS)-induced colitis in rats, and 3) to assess the effects of ghrelin treatment on mRNA expression for iNOS and protein expression for COX-2 and PPAR in intact colonic mucosa and in that with TNBS-induced colitis. Fifteen patients with UC and fifteen healthy controls were enrolled in this study. Expression of ghrelin and TNF- was assessed by semi-quantitative RT-PCR in the colonic mucosal biopsies from UC patients and healthy controls. In addition, the effect of exogenous ghrelin on healing of TNBS colitis was tested in rats without or with capsaicin-induced functional ablation of sensory nerves. Patients with UC showed a significant upregulation of mRNA for ghrelin and TNF- in colonic mucosa as compared to that observed in healthy controls. The expression of ghrelin correlated with the grade of inflammation and expression of TNF-. In rats the exogenous ghrelin administered daily at a dose of 20 µg/kg i.p. significantly accelerated the healing of TNBS colitis and this effect was accompanied by an increase in mRNA expression for iNOS and protein expression for COX-2 in the colonic mucosa. The protein expression for PPAR, which was down-regulated in rat colonic mucosa after exposure to TNBS as compared to that in intact colonic mucosa, was not significantly influenced by ghrelin treatment. We conclude that 1) patients with UC show an increased mucosal expression of mRNA for ghrelin in the colonic mucosa which could trigger protective response in inflamed colon; and 2) exogenous ghrelin accelerates healing of colonic lesions in animal model of ulcerative colitis via increased release of NO and PGE2 due to an increase in iNOS and COX-2 expression and stimulation of sensory neuropeptides such as CGRP released from sensory afferent endings.

Słowa kluczowe

EN

ulcerative colitis; orexigenic peptide; nitric oxide; antiinflammatory activity; colitis; tumour necrosis factor-alpha; inflammatory bowel disease; inflammation; sensory nerve; cyclooxygenase-2; trinitrobenze sulphonic acid; ghrelin; growth hormone

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2009
• Tom: 60
• Numer: 2
• Opis fizyczny: p.41-47,fig.,ref.

Twórcy

autor

Konturek P.C.

• University Erlangen-Nuremberg, Ulmenweg 18, 91054 Erlangen, Germany

autor

Brzozowski T.

autor

Engel M.

autor

Burnat G.

autor

Gaca P.

autor

Kwiecien S.

autor

Pajdo R.

autor

Konturek S.J.