싸이토카인 유발 췌장 β세포 독성에 대한 천화분 추출물의 방어효과
Protective Effect of Radix Trichosanthis Extracts on Cytotoxicity of Pancreatic β-Cells by Cytokines
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초록
In this study, the preventive effects of Radix Trichosanthis extracts (RTE) against cytokine-induced β-cell death were assessed. Cytokines generated by immune cells infiltrating pancreatic islets are crucial mediators of β-cell destruction in insulin-dependent diabetes mellitus. The treatment of RIN cells with interleukin-1β (IL-1β) and interferon-γ (IFN-γ) resulted in a reduction of cell viability. RTE protected IL-1β and IFN-γ-mediated viability reduction in a concentration-dependent manner. Incubation with RTE also induced a significant suppression of IL-1β and IFN-γ-induced inducible nitric oxide synthase (iNOS) protein expression. The molecular mechanism by which RTE inhibited iNOS protein expression appeared to involve the inhibition of NF-κB activation. The IL-1β and IFN-γ-stimulated RIN cells showed increases in NF-κB binding activityand IκBα degradation in cytosol compared to unstimulated cells. However, pretreatment with RTE inhibited cytokines-induced IκBα degradation and NF-κB activation in RINm5F cells. Furthermore, the protective effects of RTE were verified via protection of impairment in glucose-stimulated insulin secretions in IL-1β and IFN-γ-treated islets.
Abstract
In this study, the preventive effects of Radix Trichosanthis extracts (RTE) against cytokine-induced β-cell death were assessed. Cytokines generated by immune cells infiltrating pancreatic islets are crucial mediators of β-cell destruction in insulin-dependent diabetes mellitus. The treatment of RIN cells with interleukin-1β (IL-1β) and interferon-γ (IFN-γ) resulted in a reduction of cell viability. RTE protected IL-1β and IFN-γ-mediated viability reduction in a concentration-dependent manner. Incubation with RTE also induced a significant suppression of IL-1β and IFN-γ-induced inducible nitric oxide synthase (iNOS) protein expression. The molecular mechanism by which RTE inhibited iNOS protein expression appeared to involve the inhibition of NF-κB activation. The IL-1β and IFN-γ-stimulated RIN cells showed increases in NF-κB binding activityand IκBα degradation in cytosol compared to unstimulated cells. However, pretreatment with RTE inhibited cytokines-induced IκBα degradation and NF-κB activation in RINm5F cells. Furthermore, the protective effects of RTE were verified via protection of impairment in glucose-stimulated insulin secretions in IL-1β and IFN-γ-treated islets.
참고문헌 (22)
- Bach, J.F., "Insulin-dependent diabetes mellitus as a β-cell targeted disease of immunoregulation", Journal of Autoimmunity, 8(4), pp.39~63 (1995)
- Foulis, A.K., "The histopathology of the pancreas in type 1 (insulin-dependent) diabetes mellitus: a 25-year review of deaths in patients under 20 years of age in the United Kingdom", Diabetologia, 29, pp.267~274 (1986)
- Eizirik, D.L., "The harmony of the spheres: inducible nitric oxide synthase and related genes in pancreatic β cells", Diabetologia, 39, pp.875~890 (1996)
- Mandrup-Poulsen, T., "The role of interleukin-1β in the pathogenesis of IDDM", Diabetologia, 39, pp.1005~1029 (1996)
- Southern, C., "Inhibition of insulin secretion by interleukin-1β and tumour necrosis factor-α via an L-arginine-dependent nitric oxide generating mechanism", FEBS Letters, 276, pp.42~44 (1990)
- Eizirik, D.L., "Cytokines suppress human islet function irrespective of their effects on nitric oxide generation", Journal of Clinical Investigation, 93, pp.1968~1974 (1994)
- 신민교, "원색 임상본초학", pp.241~284 (1983), 영림출판사
- 노진구, "천화분이 실험적 당뇨 흰쥐의 췌장 내분비세포에 미치는 영향에 관한 면역세포화학적 연구", 방제학회지, 2(1), pp.97~105 (1991)
- Xie, Q.W., "Cloning and characterization of inducible nitric oxide synthase from mouse macrophages", Science, 256, pp.225~228 (1992)
- Jeong, J.Y., "Chloroquine inhibits processing of tumor necrosis factor in lipopolysaccharide-stimulated RAW 264.7 macrophages", Journal of Immunology, 158, pp.4901~4907 (1997)
- Kim, H.R., "Role of Ca2+ in alloxan-induced pancreatic β-cell damage", Biochimica et biophysica acta, 1227, pp.87~91 (1994)
- Bradford, M.M., "A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding", Analasis Biochememistry, 72, pp.248~254 (1976)
- Kwon, K.B., "Cortex cinnamomi extract prevents streptozotocin- and cytokine-induced β-cell damage by inhibiting NF-κB", World Journal of Gastroenterol, 12, pp.4331~4337 (2006)
- Kwon, K.B., "Amomum xanthoides extract prevents cytokine-induced cell death of RINm5F cells through the inhibition of nitric oxide formation", Life Sciences, 73, pp.181~191 (2003)
- Kwon, K.B., "Fructus Benincasae Recens extract prevents cytokine-induced nitric oxide formation and cytotoxicity of RINm5F cells", Immunopharmacology & Immunotoxicology, 25, pp.615~625 (2003)
- 김은경, "권강범", Coptidis rhizoma extract protects against cytokine-induceddeath of pancreatic β-cells through suppression of NF-κBactivation, 2007, pp.39(2), 149~159[DOI]
- Kim, E.K., "Inhibitory effect of Artemisia capillaris extract on cytokine-induced nitric oxide formation and cytotoxicity of RINm5F cells", International Journal of Molecular Medicine, 19(3), pp.535~540 (2007)
- Southern, C., "Inhibition of insulin secretion by interleukin-1β and tumour necrosis factor-α via an L-arginine-dependent nitric oxide generating mechanism", FEBS Lett, 276, pp.42~44 (1990)
- Welsh, N., "Interleukin-1-induced nitric oxide production in isolated rat pancreatic islets requires gene transcription and may lead to inhibition of the Krebs cycle enzyme aconitase", Endocrinology, 129, pp.3167~3173 (1991)
- Eizirik, D.L., "The harmony of the spheres: inducible nitric oxide synthase and related genes in pancreatic β cells", Diabetologia, 39, pp.875~890 (1996)
- Baeuerle, P.A., "Function and activation of NF-κB in the immune system", Annual Review of Immunology, 12, pp.141~179 (1994)
- Baldwin, A.S., "The NF-κB and IκB proteins: new discoveries and insights", Annual Review of Immunology, 14, pp.649~683 (1996)