2009年 02月 08日 ( 2 )

 

Toll-like receptor

日曜なので、私の初学的お勉強

本来、
Toll-like receptor control of the adaptive immune responses
Nature Immunology 5, 987 - 995 (2004)
から勉強すべきなのだろうが・・・初歩のお勉強なので・・文献検索すると、2005年以降基礎的報告が少なくなり、そのburdenの広がりと基礎的知識の深まりがじんわりと・・・という感じか?

”LPS、IFN-γ、酸化LDL→外因性リガンド - TLR4”ってことで、各種感染症(肺炎球菌、肺結核、ナイセリア・・・)や動脈硬化など幅広い関連が今世紀になって検討されている。感染症においては、LPSによるTLR認識が”central regulator of effective host immunity to bacterial pathogens”と考えられ、また、TLR-2はグラム陽性菌細胞壁のリポタイコ酸やペプチドグリカンを認識、TLR5は細菌鞭毛蛋白フラジェリン認識、細菌DNAやウィルスDNAもリガンドとして作用、真菌・原虫の構成成分も認識することが報告されている。RSVではTLR4が融合蛋白の認識に関わり、合成dsRNAとTLR3との関連、TLR9やTLR7などもウィルスの認識に関わる(ウィルス vol. 54 (2) 145-152, 2004


Toll-like receptors (TLRs) recognize distinct pathogen-associated molecular patterns and play a critical role in innate immune responses. They participate in the first line of defense against invading pathogens and play a significant role in inflammation, immune cell regulation, survival and proliferation. To date 11 members of the TLR family have been identified, of which TLR1, 2, 4, 5 and 6 are located on the cell surface and TLR3, 7, 8 and 9 are localized to the endosomal/lysosomal compartment. The activation of the TLR signaling pathway originates from the cytoplasmic Toll/IL-1 receptor (TIR) domain that associates with a TIR domain-containing adaptor, MyD88. Upon stimulation with ligands, MyD88 recruits IL-1 receptor-associated kinase (IRAK) to TLRs through interaction of the death domains of both molecules. IRAK activated by phosphorylation then associates with TRAF6, finally leading to activation of JNK and NF-κB. Tollip and IRAK-M interact with IRAK-1 and negatively regulate the TLR-mediated signaling pathways. MyD88-independent pathways induce activation of IRF3 and expression of interferon-β. TIR-domain containing adaptors such as TIRAP, TRIF and TRAM regulate TLR-mediated signaling pathways by providing specificity for individual TLR signaling cascades.


(http://www.cellsignal.com/reference/pathway/Toll_Like.html)


Molecular surface of toll-like receptor




Toll様受容体は、主として微生物感染を感知して、Th1を誘導するシステムで、NK細胞らと共に自然免疫に関わっている。・・・




http://allatopy.wakabagari.com/sigu/sigu15.html


http://www.ariadnegenomics.com/products/pathway-studio/sample-pathways/toll-like-receptor/


肺炎球菌とTLR
Toll-Like Receptor 2 Deficiency Delays Pneumococcal Phagocytosis and Impairs Oxidative Killing by Granulocytes
Infection and Immunity, December 2005, p. 8397-8401, Vol. 73, No. 12


インフルエンザとTLR
the model involves mitogen-activated protein kinases, phosphatidylinositol 3-kinase/Akt signaling, and the TLR3-associated adaptor molecule TRIF but not MyD88-dependent activation of the transcription factors NF-{kappa}B or interferon regulatory factor/interferon-sensitive response-element pathways.
Involvement of Toll-like Receptor 3 in the Immune Response of Lung Epithelial Cells to Double-stranded RNA and Influenza A Virus
J. Biol. Chem., Vol. 280, Issue 7, 5571-5580, February 18, 2005
its evasion by viruses and a potential role in crosspriming is addressed, which reveals a clearer appreciation of the contribution of TLR3 to antiviral immunity.
TLR3 in antiviral immunity: key player or bystander?
Trends in Immunology Volume 26, Issue 9, September 2005, Pages 462-468


動脈硬化とTLR
Review:The toll of Toll-like receptors, especially toll-like receptor 2, on murine atherosclerosis.
Curr Drug Targets. 2007 Dec;8(12):1230-8.

Toll-like receptors (TLRs) – which sense microbial pathogens and initiate immediate inflammatory responses – are potentially involved in the pathogenesis of atherosclerosis.
Toll-like receptors and atherosclerosis: oxidized LDL as an endogenous Toll-like receptor ligand
Future Cardiology, Volume 1, Number 6, November 2005 , pp. 785-792(8)

by internalmedicine | 2009-02-08 08:44 | 医学  

虚血性心疾患と間質性肺炎の関係?

筆者らは、間質性肺炎の原因としてスタチンを想定してた模様

症例対照だし、あえて紹介しなくて良かったと、今は反省

Association between ischaemic heart disease and interstitial lung disease: A case–control study
Respiratory Medicine doi:10.1016/j.rmed.2009.01.004

ある医療機関での症例対照検討で、
IPFにおいて スタチン使用 12/50 vs 未使用 20/100(matched OR 1.13, CI 0.30-4.24)

冠動脈疾患は12/50 vs 対照 20/100 (matched OR 5.37, CI 1.52–19.0, p < 0.01)


なんか、キリ良すぎるのだが・・・

by internalmedicine | 2009-02-08 08:31 | 呼吸器系