Tumour necrosis factor activates the mitogen-activated protein kinases p38α and ERK in the synovial membrane in vivo 英文参考文献.docVIP

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Tumour necrosis factor activates the mitogen-activated protein kinases p38α and ERK in the synovial membrane in vivo 英文参考文献.doc

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Tumour necrosis factor activates the mitogen-activated protein kinases p38α and ERK in the synovial membrane in vivo 英文参考文献

Available online /content/7/5/R1140 Research article Open Access Vol 7 No 5 Tumour necrosis factor activates the mitogen-activated protein kinases p38α and ERK in the synovial membrane in vivo Birgit G?rtz1,2, Silvia Hayer1, Birgit Tuerck1, Jochen Zwerina1, Josef S Smolen1 and Georg Schett1 1Division of Rheumatology, Department of Internal Medicine III, University of Vienna, Vienna, Austria 2Institute of Pathology, University of Giessen, Giessen, Germany Corresponding author: Georg Schett, georg.schett@meduniwien.ac.at Received: 9 May 2005 Revisions requested: 14 Jun 2005 Revisions received: 27 Jun 2005 Accepted: 28 Jun 2005 Published: 28 Jul 2005 Arthritis Research Therapy 2005, 7:R1140-R1147 (DOI 10.1186/ar1797) This article is online at: /content/7/5/R1140 ? 2005 G?rtz et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (/licenses/by/ 2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Tumour necrosis factor (TNF) is considered to be a major factor in chronic synovial inflammation and is an inducer of mitogen- activated protein kinase (MAPK) signalling. In the present study we investigated the ability of TNF to activate MAPKs in the synovial membrane in vivo. We studied human TNF transgenic mice – an in vivo model of TNF-induced arthritis – to examine phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun amino terminal kinase (JNK) and p38MAPKα in the immunohistochemical analysis. Activated p38MAPKα was predominantly found in synovial macrophages, whereas ERK activation was present in both synovial macrophages and fibroblasts. T and B lymphocytes did not exhibit major activation of any of the three MAPKs. Systemic blockade of TNF reduced activation of p38MAPKα and ERK, whereas inhibition of IL-1 only affected p38MAP