본문 바로가기
KERD
논문KCI 등재

Celastrol suppresses expression of adhesion molecules and chemokines by inhibiting JNK-STAT1/NF-κB activation in poly(I:C)-stimulated astrocytes

0

조회

0

다운로드

3

인용

0

참고문헌

키워드

주제분류화학

초록

In the central nervous system, viral infection can induce inflammation by up-regulating pro-inflammatory mediators that contribute to enhanced infiltration of immune cells into the central nervous areas. Celastrol is known to exert various regulatory functions, including anti-microbial activities. In this study, we investigated the regulatory effects and the mechanisms of action of celastrol against astrocytes activated with polyinosinic-polycytidylic acid (poly(I:C)), a synthetic dsRNA, as a model of pro-inflammatory mediated responses. Celastrol significantly inhibited poly(I:C)-induced expression of adhesion molecules, such as ICAM-1/VCAM-1, and chemokines, such as CCL2, CXCL8, and CXCL10, in CRT-MG human astroglioma cells. In addition, celastrol significantly suppressed poly(I:C)-induced activation of JNK MAPK and STAT1 signaling pathways. Furthermore, celastrol significantly suppressed poly(I:C)-induced activation of the NF-κB signaling pathway. These results suggest that celastrol may exert its regulatory activity by inhibiting poly(I:C)-induced expression of pro-inflammatory mediators by suppressing activation of JNK MAPK-STAT1/NF-κB in astrocytes.

Abstract

In the central nervous system, viral infection can induce inflammation by up-regulating pro-inflammatory mediators that contribute to enhanced infiltration of immune cells into the central nervous areas. Celastrol is known to exert various regulatory functions, including anti-microbial activities. In this study, we investigated the regulatory effects and the mechanisms of action of celastrol against astrocytes activated with polyinosinic-polycytidylic acid (poly(I:C)), a synthetic dsRNA, as a model of pro-inflammatory mediated responses. Celastrol significantly inhibited poly(I:C)-induced expression of adhesion molecules, such as ICAM-1/VCAM-1, and chemokines, such as CCL2, CXCL8, and CXCL10, in CRT-MG human astroglioma cells. In addition, celastrol significantly suppressed poly(I:C)-induced activation of JNK MAPK and STAT1 signaling pathways. Furthermore, celastrol significantly suppressed poly(I:C)-induced activation of the NF-κB signaling pathway. These results suggest that celastrol may exert its regulatory activity by inhibiting poly(I:C)-induced expression of pro-inflammatory mediators by suppressing activation of JNK MAPK-STAT1/NF-κB in astrocytes.

참고문헌 (26)

  1. Arroyo DS, "Toll-like receptors are key players in neurodegeneration", Int Immunopharmacol, 11, pp.1415~1421 (2011)
  2. Zhang SY, "TLR3 immunity to infection in mice and humans", Curr Opin Immunol, 25, pp.19~33 (2013)
  3. Salmina AB, "Astroglial control of neuroinflammation: TLR3-mediated dsRNA-sensing pathways are in the focus", Rev Neurosci, 26, pp.143~159 (2015)
  4. Farina C, "Preferential expression and function of Toll-like receptor 3 in human astrocytes", J Neuroimmunol, 159, pp.12~19 (2005)
  5. Bsibsi M, "Toll-like receptor 3 on adult human astrocytes triggers production of neuroprotective mediators", Glia, 53, pp.688~695 (2006)
  6. Park C, "TLR3-mediated signal induces proinflammatory cytokine and chemokine gene expression in astrocytes: differential signaling mechanisms of TLR3-induced IP-10 and IL-8 gene expression", Glia, 53, pp.248~256 (2006)
  7. Kim H, "Double-stranded RNA mediates interferon regulatory factor 3 activation and interleukin-6 production by engaging Toll-like receptor 3 in human brain astrocytes", Immunology, 124, pp.480~488 (2008)
  8. Gorina R, "Astrocytes are very sensitive to develop innate immune responses to lipid-carried short interfering RNA", Glia, 57, pp.93~107 (2009)
  9. Scumpia PO, "Double-stranded RNA signals antiviral and inflammatory programs and dysfunctional glutamate transport in TLR3-expressing astrocytes", Glia, 52, pp.153~162 (2005)
  10. So EY, "Induction of chemokine and cytokine genes in astrocytes following infection with Theiler's murine encephalomyelitis virus is mediated by the Toll-like receptor 3", Glia, 53, pp.858~867 (2006)
  11. Allison AC, "Celastrol, a potent antioxidant and anti-inflammatory drug, as a possible treatment for Alzheimer's disease", Prog Neuropsychopharmacol Biol Psychiatry, 25, pp.1341~1357 (2001)
  12. 주성미, "Celastrol ameliorates cytokine toxicity and pro-inflammatory immune responses by suppressing NF-κB activation in RINm5F beta cells", BMB Reports, 48(3), pp.172~177 (2015), 생화학분자생물학회
  13. Hyo Won Jung, "Celastrol inhibits production of nitric oxide and proinflammatorycytokines through MAPK signal transduction and NF-κB inLPS-stimulated BV-2 microglial cells", Experimental and Molecular Medicine, 39(6), pp.715~721 (2007), 생화학분자생물학회
  14. Nakamichi K, "Celastrol suppresses morphological and transcriptional responses in microglial cells upon stimulation with double-stranded RNA", Int J Neurosci, 120, pp.252~257 (2010)
  15. Narayan V, "Celastrol inhibits Tat-mediated human immunodeficiency virus (HIV) transcription and replication", J Mol Biol, 410, pp.972~983 (2011)
  16. Youn GS, "Celastrol ameliorates HIV-1 Tat-induced inflammatory responses via NF-kappaB and AP-1 inhibition and heme oxygenase-1 induction in astrocytes", Toxicol Appl Pharmacol, 280, pp.42~52 (2014)
  17. Imaizumi T, "Desferrioxamine, an iron chelator, inhibits CXCL10 expression induced by polyinosinic-polycytidylic acid in U373MG human astrocytoma cells", Neurosci Res, 94, pp.10~16 (2015)
  18. Lee CS, "Inhibition of doublestranded RNA-induced inducible nitric oxide synthase expression by fraxinellone and sauchinone in murine microglia", Biol Pharm Bull, 32, pp.1870~1874 (2009)
  19. 서진원, "An inhibitory alternative splice isoform of Toll-like receptor 3 is induced by type I interferons in human astrocyte cell lines", BMB Reports, 48(12), pp.696~701 (2015), 생화학분자생물학회
  20. Melchjorsen J, "Expression and function of chemokines during viral infections: from molecular mechanisms to in vivo function", J Leukoc Biol, 74, pp.331~343 (2003)
  21. Ramesh G, "Cytokines and chemokines at the crossroads of neuroinflammation, neurodegeneration, and neuropathic pain", Mediators Inflamm, 2013, pp.480739~ (2013)
  22. Lee JH, "Inhibition of NF-kappa B activation through targeting I kappa B kinase by celastrol, a quinone methide triterpenoid", Biochem. Pharmacol, 72, pp.1311~1321 (2006)
  23. 김혜진, "2,3-Dimethoxy-2′-hydroxychalcone ameliorates TNF-α-induced ICAM-1 expression and subsequent monocyte adhesiveness via NF-kappaB inhibition and HO-1 induction in HaCaT cells", BMB Reports, 49(1), pp.57~62 (2016), 생화학분자생물학회
  24. Youn GS, "HDAC6 mediates HIV-1 tat-induced proinflammatory responses by regulating MAPK-NF-kappaB", AP-1 pathways in astrocytes, 2015, pp.63, 1953~1965
  25. 권동주, "Salicortin suppresses lipopolysaccharide-stimulated inflammatory responses via blockade of NF-κB and JNK activation in RAW 264.7 macrophages", BMB Reports, 47(6), pp.318~323 (2014), 생화학분자생물학회
  26. 서원영, "Butein, a tetrahydroxychalcone, suppresses pro-inflammatory responses in HaCaT keratinocytes", BMB Reports, 48(9), pp.495~500 (2015), 생화학분자생물학회

관련 논문AI추천

Celastrol ameliorates cytokine toxicity and pro-inflammatory immune responses by suppressing NF-κB activation in RINm5F beta cells박진서, 윤기수, 조윤신, 주성미, 최수영생화학분자생물학회 · BMB Reports2015 · 제48권 제3호Hindsiipropane B alleviates HIV-1 Tat-induced inflammatory responses by suppressing HDAC6-NADPH oxidase-ROS axis in astrocytes김동규, 박진서, 윤기수, 이채연, 장재희, 장하영, 전종갑, 조현동, 최수영생화학분자생물학회 · BMB Reports2018 · 제51권 제8호An inhibitory alternative splice isoform of Toll-like receptor 3 is induced by type I interferons in human astrocyte cell lines김세훈, 서진원, 양은정, 최인홍생화학분자생물학회 · BMB Reports2015 · 제48권 제12호Effects of 3′-isovaleryl-4′-senecioylkhellactone from Peucedanum japonicum Thunberg on PMA-Stimulated Inflammatory Response in A549 Human Lung Epithelial Cells류형원, 안경섭, 한상배, Hwang Daseul, Kim Doo-Young, Kim Jung-Hee, Kwon Ok-Kyoung, Oh Jae-Hoon, Park Ji-Won한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2022 · 제32권 제1호Anti-inflammatory Effects of Gastrodia elata Extract in Lipopolysaccharide-stimulated BV-2 Microglia Cell김재규, 서영경, 이준혁, 장지연, 최나현, 최병태, 허영현한의병리학회 · 동의생리병리학회지2012 · 제26권 제5호Paeoniflorin ameliorates Aβ-stimulated neuroinflammation via regulation of NF-κB signaling pathway and Aβ degradation in C6 glial cellsCho Eun Ju, Kim Hyun Young, Lee Ah Young한국영양학회 · Nutrition Research and Practice2020 · 제14권 제6호

이 간행물의 다른 논문 (9건)