PMID- 21091668 OWN - NLM STAT- MEDLINE DCOM- 20110203 LR - 20211020 IS - 1365-2249 (Electronic) IS - 0009-9104 (Print) IS - 0009-9104 (Linking) VI - 163 IP - 2 DP - 2011 Feb TI - Toll-like receptor (TLR)-4 mediates anti-beta2GPI/beta2GPI-induced tissue factor expression in THP-1 cells. PG - 189-98 LID - 10.1111/j.1365-2249.2010.04291.x [doi] AB - Our previous study demonstrated that annexin A2 (ANX2) on cell surface could function as a mediator and stimulate tissue factor (TF) expression of monocytes by anti-beta(2)-glycoprotein I/beta(2)-glycoprotein I complex (anti-beta(2)GPI/beta(2)GPI). However, ANX2 is not a transmembrane protein and lacks the intracellular signal transduction pathway. Growing evidence suggests that Toll-like receptor 4 (TLR-4) might act as an 'adaptor' for intracellular signal transduction in anti-beta(2)GPI/beta(2)GPI-induced TF expressing cells. In the current study, we investigated the roles of TLR-4 and its related molecules, myeloid differentiation protein 2 (MD-2) and myeloid differentiation factor 88 (MyD88), in anti-beta(2)GPI/beta(2)GPI-induced TF expressing human monocytic-derived THP-1 (human acute monocytic leukaemia) cells. The relationship of TLR-4 and ANX2 in this process was also explored. Along with TF, expression of TLR-4, MD-2 and MyD88 in THP-1 cells increased significantly when treated by anti-beta(2)GPI (10 microg/ml)/beta(2)GPI (100 microg/ml) complex. The addition of paclitaxel, which competes with the MD-2 ligand, could inhibit the effects of anti-beta(2)GPI/beta(2)GPI on TLR-4, MD-2, MyD88 and TF expression. Both ANX2 and TLR-4 in THP-1 cell lysates could bind to beta(2)GPI that had been conjugated to a column (beta(2)GPI-Affi-Gel). Furthermore, TLR-4, MD-2, MyD88 and TF expression was remarkably diminished in THP-1 cells infected with ANX2-specific RNA interference (RNAi) lentivirus (LV-RNAi-ANX2), in spite of treatment with a similar concentration of anti-beta(2)GPI/beta(2)GPI complex. These results indicate that TLR-4 and its signal transduction pathway contribute to anti-beta(2)GPI/beta(2)GPI-induced TF expression in THP-1 cells, and the effects of TLR-4 with ANX2 are tightly co-operative. CI - (c) 2010 The Authors. Clinical and Experimental Immunology (c) 2010 British Society for Immunology. FAU - Zhou, H AU - Zhou H AD - Department of Clinical Laboratory and Hematology, Jiangsu University, Zhenjiang, China. hongzhou@ujs.edu.cn FAU - Yan, Y AU - Yan Y FAU - Xu, G AU - Xu G FAU - Zhou, B AU - Zhou B FAU - Wen, H AU - Wen H FAU - Guo, D AU - Guo D FAU - Zhou, F AU - Zhou F FAU - Wang, H AU - Wang H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101122 PL - England TA - Clin Exp Immunol JT - Clinical and experimental immunology JID - 0057202 RN - 0 (Annexin A2) RN - 0 (Antibodies, Antiphospholipid) RN - 0 (LY96 protein, human) RN - 0 (Lymphocyte Antigen 96) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (TLR4 protein, human) RN - 0 (Toll-Like Receptor 4) RN - 0 (beta 2-Glycoprotein I) RN - 9035-58-9 (Thromboplastin) RN - P88XT4IS4D (Paclitaxel) SB - IM MH - Annexin A2/metabolism MH - Antibodies, Antiphospholipid/*immunology MH - Antiphospholipid Syndrome/*immunology MH - Cell Line MH - Humans MH - Lymphocyte Antigen 96/metabolism MH - Monocytes/drug effects/immunology MH - Myeloid Differentiation Factor 88/metabolism MH - Paclitaxel/pharmacology MH - Thromboplastin/*biosynthesis MH - Toll-Like Receptor 4/*metabolism MH - beta 2-Glycoprotein I/*antagonists & inhibitors/immunology PMC - PMC3043309 EDAT- 2010/11/26 06:00 MHDA- 2011/02/04 06:00 PMCR- 2012/02/01 CRDT- 2010/11/25 06:00 PHST- 2010/11/25 06:00 [entrez] PHST- 2010/11/26 06:00 [pubmed] PHST- 2011/02/04 06:00 [medline] PHST- 2012/02/01 00:00 [pmc-release] AID - 10.1111/j.1365-2249.2010.04291.x [doi] PST - ppublish SO - Clin Exp Immunol. 2011 Feb;163(2):189-98. doi: 10.1111/j.1365-2249.2010.04291.x. Epub 2010 Nov 22.