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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
- 2015.1
- 수록면
- 26 - 32 (7page)
- DOI
- 10.14348/molcells.2015.2136
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초록· 키워드
오류제보하기
Toll-like receptors (TLR) 7 and 9 transduce a cellular signal through the MyD88-dependent pathway and induce the production of inflammatory mediators against microbial nucleotide components. The repeated stimulation of TLR4 leads to endotoxin tolerance, but the molecular mechanisms of tolerance induced through the costimulation of individual TLR has not yet been established, although endosomal TLRs share signaling pathways with TLR4. In the present study, mouse macrophages were simultaneously stimulated with the TLR7 agonist, gardiquimod (GDQ), and the TLR9 agonist, CpG ODN 1826, to examine the mechanism and effector functions of macrophage tolerance. Compared with individual stimulation, the costimulation of both TLRs reduced the secretion of TNF-α and IL-6 through the delayed activation of the NF-κB pathway; notably, IL-10 remained unchanged in costimulated macrophages. This tolerance reflected the early induction of suppressor of cytokine signaling-1 (SOCS-1), according to the detection of elevated TNF-α secretion and restored NF-κB signaling in response to the siRNA-mediated abrogation of SOCS-1 signaling. In addition, the restimulation of each TLRs using the same ligand significantly reduced the expression of both TLRs in endosomes. These findings revealed that the costimulation of TLR7 and TLR9 induced macrophage tolerance via SOCS-1, and the restimulation of each receptor or both TLR7 and TLR9 downregulated TLR expression through a negative feedback mechanisms that protects the host from excessive inflammatory responses. Moreover, the insufficient and impaired immune response in chronic viral infection might also reflect the repeated and simultaneous stimulation of those endosomal TLRs.
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등록된 정보가 없습니다.
참고문헌 (25)
참고문헌 신청
Akira, S. / 2009 / Innate immunity to pathogens : diversity in receptors for microbial recognition / Immunol. Rev 227:5~8
Chang, Z. L. / 2010 / Important aspects of Toll-like receptors, ligands and their signaling pathways / Inflamm. Res 59:791~808
Chang, J. J. / 2012 / Differential regulation of toll-like receptor pathways in acute and chronic HIV-1 infection / Aids 26:533~541
Chen, W. H. / 2012 / Potential role for alternatively activated macrophages in the secondary bacterial infection during recovery from influenza / Immunol. Lett 141:227~234
Cross, A. / 1995 / The importance of a lipopolysaccharide-initiated, cytokine-mediated host defense mechanism in mice against extraintestinally invasive Escherichia coli / J. Clin. Invest 96:676~686
Chang, Z. L. / 2010 / Important aspects of Toll-like receptors, ligands and their signaling pathways / Inflamm. Res 59:791~808
Chang, J. J. / 2012 / Differential regulation of toll-like receptor pathways in acute and chronic HIV-1 infection / Aids 26:533~541
Chen, W. H. / 2012 / Potential role for alternatively activated macrophages in the secondary bacterial infection during recovery from influenza / Immunol. Lett 141:227~234
Cross, A. / 1995 / The importance of a lipopolysaccharide-initiated, cytokine-mediated host defense mechanism in mice against extraintestinally invasive Escherichia coli / J. Clin. Invest 96:676~686
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