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Melatonin modulates signal transduction pathways and apoptosis in experimental colitis
Author(s) -
Mazzon Emanuela,
Esposito Emanuela,
Crisafulli Concetta,
Riccardi Luisa,
Muià Carmelo,
Bella Paolo Di,
Meli Rosaria,
Cuzzocrea Salvatore
Publication year - 2006
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2006.00378.x
Subject(s) - melatonin , colitis , signal transduction , inflammatory bowel disease , apoptosis , tunel assay , fas ligand , endocrinology , medicine , inflammation , chemistry , pharmacology , biology , cancer research , microbiology and biotechnology , immunology , programmed cell death , biochemistry , disease
Various evidences have documented that the pineal secretory product melatonin exerts an important anti‐inflammatory effect in different experimental models including colitis. The aim of the present study was to evaluate whether melatonin regulates the inflammatory response of experimental colitis in rats at the level of signal transduction pathway. Colitis was induced by intracolonic instillation of dinitrobenzene sulfonic acid (DNBS). Four days after DNBS administration, a substantial increase of colon TNF‐ α production was associated with the colon damage. In DNBS‐treated rats, the colon injury correlated with a significant rise of apoptosis (evaluated by TUNEL coloration) which was associated with a significant increased expression of proapoptotic Bax and decreased colon content of antiapoptotic Bcl‐2. This inflammatory response was also related to activation of nuclear factor‐ κ B (NF‐ κ B) and phosphorylation of c‐Jun as well as FAS ligand expression in the colon. Treatment with melatonin (15 mg/kg daily i.p.) was associated with a remarkable amelioration of colonic disrupted architecture as well as a significant reduction of TNF‐ α . Melatonin also reduced the NF‐ κ B activation and phosphorylation of c‐Jun as well as the Fas ligand expression in the colon. Furthermore, melatonin reduced the expression of Bax and prevented the loss of Bcl‐2 proteins as well as the presence of apoptotic cells caused by DNBS. The results of this study show that melatonin administration exerts beneficial effects in inflammatory bowel disease by modulating signal transduction pathways.