title: Protective effect of retinoic acid on interleukin-1 beta-induced cytotoxicity of pancreatic beta-cells.
abstract: Cytokines produced by immune cells in pancreatic islets infiltrating are important mediators of beta-cell destruction in insulin-dependent diabetes mellitus. In this study, the effects of retinoic acid (RA) on cytokine-induced beta-cell dysfunction were examined. RA significantly protected interleukin-1 beta (IL-1) and interferon-gamma (IFN-gamma)-mediated cytotoxicity of rat insulinoma cell (RINm5F), and also reduced in IL-1 and IFN-gamma-induced nitric oxide (NO) production, which correlated well with reduced levels of the inducible form of NO synthase (iNOS) mRNA and protein. The molecular mechanism, by which RA inhibited iNOS gene expression, appeared to involve the inhibition of NF-kappa B activation. Our results suggest possible therapeutic value of RA for the prevention of diabetes mellitus progression.
authors.affiliation: Department of Oral Biochemistry, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju 561-756, South Korea.
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Kang
authors.forename: Yeo-Eun
authors.initials: YE
authors.lastname: Yoon
authors.forename: Jeong-Yeh
authors.initials: JY
authors.lastname: Yang
authors.forename: Kang-Beom
authors.initials: KB
authors.lastname: Kwon
authors.forename: Jin-Woo
authors.initials: JW
authors.lastname: Park
authors.forename: Eun-Chung
authors.initials: EC
authors.lastname: Jhee
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007340:Insulinoma / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D007375:Interleukin-1 / Q000633:toxicity*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000473:pathology; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D007375:Interleukin-1; D016328:NF-kappa B; D009573:Nitrites; D020011:Protective Agents; D009569:Nitric Oxide; D014212:Tretinoin; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019331:NG-Nitroarginine Methyl Ester