지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2015.3
- 수록면
- 11 - 16 (6page)
이용수
초록· 키워드
오류제보하기
Our body’s immune system has defense mechanisms against pathogens such as viruses and bacteria. Immune responses are primarily initiated by the activation of toll-like receptors (TLRs). In particular, TLR4 is well-characterized and is known to be activated by gram-negative bacteria and tissue damage signals. TLR4 requires myeloid differentiation factor 2 (MD2) as a co-receptor to recognize its ligand, lipopolysaccharides (LPS), which is an extracellular membrane component of gram-negative bacteria. Gambogic acid is a xanthonoid isolated from brownish or orange resin extracted from Garcinia hanburyi. Its primary effect is tumor suppression. Since inflammatory responses are related to the development of cancer, we hypothesized that gambogic acid may regulate TLR4 activation. Our results demonstrated that gambogic acid decreased the expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-12, and IL-1β) in both mRNA and protein levels in bone marrow-derived primary macrophages after stimulation with LPS. Gambogic acid did not inhibit the activation of Interferon regulatory factor 3 (IRF3) induced by TBK1 overexpression in a luciferase reporter gene assay using IFN-β-PRD III-I-luc. An in vitro kinase assay using recombinant TBK1 revealed that gambogic acid did not directly inhibit TBK1 kinase activity, and instead suppressed the binding of LPS to MD2, as determined by an in vitro binding assay and confocal microscopy analysis. Together, our results demonstrate that gambogic acid disrupts LPS interaction with the TLR4/MD2 complex, the novel mechanism by which it suppresses TLR4 activation.
목차
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
참고문헌 (14)
참고문헌 신청
Takeda, K. / 2003 / Toll-like receptors / Annu. Rev. Immunol. 21:335~376
Dixon, D.R. / 2005 / Lipopolysaccharides heterogeneity: innate host responses to bacterial modification of lipid a structure / J. Dent. Res. 84:584~595
Park, B. S. / 2009 / The structural basis of lipopolysaccharides recognition by the TLR4-MD-2 complex / Nature 458:1191~1195
Geng, J. / 2013 / Gambogic acid protects from endotoxin shock by suppressing pro-inflammatory factors in vivo and in vitro / Inflammation Res. 62:165~172
Kim, S. Y. / 2013 / Suppression of Toll-like receptor 4 activation by caffeic acid phenethyl ester is mediated by interference of LPS binding to MD2 / Br. J. Pharmacol. 168:1933~1945
Dixon, D.R. / 2005 / Lipopolysaccharides heterogeneity: innate host responses to bacterial modification of lipid a structure / J. Dent. Res. 84:584~595
Park, B. S. / 2009 / The structural basis of lipopolysaccharides recognition by the TLR4-MD-2 complex / Nature 458:1191~1195
Geng, J. / 2013 / Gambogic acid protects from endotoxin shock by suppressing pro-inflammatory factors in vivo and in vitro / Inflammation Res. 62:165~172
Kim, S. Y. / 2013 / Suppression of Toll-like receptor 4 activation by caffeic acid phenethyl ester is mediated by interference of LPS binding to MD2 / Br. J. Pharmacol. 168:1933~1945
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UCI(KEPA) : I410-ECN-0101-2016-513-001366422