Radix asari extract protects pancreatic beta cells against cytokine-induced toxicity: implication of the NF-kappaB-iNOS signaling cascade.
In this study, we assessed the preventive effects of Radix asari extract (RAE) against cytokine-induced beta-cell destruction. Cytokines secreted by immune cells that have infiltrated pancreatic islets are crucial mediators of beta-cell destruction in insulin-dependent diabetes mellitus. Treatment of RINm5F (RIN) cells with interleukin (IL)-1beta and interferon (IFN)-gamma resulted in a reduction of cell viability and proliferation. However, treatment of RIN cells with RAE protected the IL-1beta and IFN-gamma- mediated viability and proliferation reduction in a concentration-dependent manner. Incubation with RAE also resulted in significant suppression of IL-1beta and IFN-gamma-induced nitric oxide (NO) production, and this reduction was correlated with reduced levels of mRNA and protein associated with the inducible form of NO synthase (iNOS). The molecular mechanism by which RAE inhibited iNOS gene expression appeared to involve the inhibition of NF-kappaB activation as a result of RAE's suppression of IL-1beta and IFN-gamma-induced IkappaBalpha degradation. The protective effects of RAE were verified via the observation of reduced NO generation and iNOS expression, as well as the observation of normal insulin-secretion responses to glucose in IL-1beta and IFN-gamma-treated rat islets. These results suggest that RAE protects beta cells from cytokine toxicity by suppression of NF-kappaB activation.
Song
Mi-Young
MY
Department of Biochemistry, Medical School and Institute for Medical Sciences, Chonbuk National University, Jeonju, Jeonbuk 561-756, Korea.
Kim
Kyung-Ah
KA
Lee
Su-Yeop
SY
Kim
Eun-Kyung
EK
Lv
Na
N
Lee
Ji-Hyun
JH
Park
Jin-Woo
JW
Ryu
Do-Gon
DG
Kwon
Kang-Beom
KB
Park
Byung-Hyun
BH
D000818:Animals; D029065:Aristolochiaceae; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D019610:Cytoprotection / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D007371:Interferon-gamma / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
D016207:Cytokines; D007328:Insulin; D053583:Interleukin-1beta; D016328:NF-kappa B; D010936:Plant Extracts; D012333:RNA, Messenger; D009569:Nitric Oxide; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; D005947:Glucose