Protective effect of retinoic acid on interleukin-1 beta-induced cytotoxicity of pancreatic beta-cells.
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.
Kang
Mi-Kyung
MK
Department of Oral Biochemistry, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju 561-756, South Korea.
Yoon
Yeo-Eun
YE
Yang
Jeong-Yeh
JY
Kwon
Kang-Beom
KB
Park
Jin-Woo
JW
Jhee
Eun-Chung
EC
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*
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