Fructus Xanthii extract protects against cytokine-induced damage in pancreatic beta-cells through suppression of NF-kappaB activation.
Cytokines released by infiltrating inflammatory cells around the pancreatic islets are involved in the pathogenesis of type 1 diabetes. Interleukin (IL)-1beta and interferon (IFN)-gamma are the primary cytokines responsible for stimulation of inducible nitric oxide synthase (iNOS) expression and nitric oxide overproduction, which leads to beta-cell damage. In addition, nuclear factor-kappaB (NF-kappaB) plays a crucial role in the activation of this pathway. Therefore, suppression of the cytokine-NF-kappaB pathway is considered an effective therapeutic strategy for preventing inflammatory reactions in pancreatic beta-cells. In this study, the effects of Fructus Xanthii extract (FXE) on IL-1beta and IFN-gamma-induced beta-cell damage were examined. Treatment of RINm5F cells with IL-1beta and IFN-gamma reduced cell viability, however, FXE completely protected cells from IL-1beta and IFN-gamma-mediated reduction in viability in a concentration-dependent manner. In addition, incubation with FXE resulted in a significant suppression of IL-1beta and IFN-gamma-induced nitric oxide (NO) production, which correlated with the reduced levels of the inducible form of iNOS mRNA and protein observed. The IL-1beta and IFN-gamma-stimulated RIN cells showed increases in NF-kappaB binding activity and p50 subunit levels in the nucleus, as well as increased IkappaBalpha degradation in cytosol when compared to unstimulated cells, which indicates that the mechanism by which FXE inhibited the iNOS gene involves inhibition of NF-kappaB activation. Furthermore, a protective effect of FXE was demonstrated by reduction in NO generation and iNOS expression, as well as the normal insulin secreting responses to glucose observed in IL-1beta and IFN-gamma-treated islets.
Song
Mi-Young
MY
Department of Biochemistry, Medical School and Institute for Medical Sciences, Chonbuk National University, Jeonju, Jeonbuk 561-756, Korea.
Kim
Eun-Kyung
EK
Lee
Heon-Jae
HJ
Park
Jin-Woo
JW
Ryu
Do-Gon
DG
Kwon
Kang-Beom
KB
Park
Byung-Hyun
BH
D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology*; D024202:Electrophoretic Mobility Shift Assay; D005638:Fruit / Q000737:chemistry; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007371:Interferon-gamma / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D031210:Xanthium / Q000737:chemistry*
D016207:Cytokines; D007328:Insulin; D053583:Interleukin-1beta; D016328:NF-kappa B; D009687:Nuclear Proteins; D009841:Oligonucleotides; D010936:Plant Extracts; D009569:Nitric Oxide; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; D005947:Glucose