| JNK1 deficiency limits macrophage mediated antigen-induced arthritis. | |
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MedLine Citation:
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PMID: 21305529 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVE: To elucidate the non-redundant roles of JNK1 and JNK2 in antigen-induced arthritis (AIA). METHODS: Mice that were genetically disrupted in Jnk1 or Jnk2 were primed with methylated BSA (mBSA) in complete Freund's adjuvant and then given an intraarticular challenge with mBSA in the knee on day 21. Bone marrow chimeras were generated and similarly treated. Joints were harvested and prepared for histological assessment. T cell responses were verified by cytokine and proliferation responses, and relative immunoglobulin responses were measured by ELISA. Cytokine mRNA expression levels were measured by qPCR. Thioglycollate and zymosan A elicited macrophage recruitment was tested in vivo and migration was tested in vitro. The peptide inhibitor D-JNKi was injected daily starting four days after intraarticular mBSA injection in wild type (WT) mice and inflammation was histologically scored. RESULTS: JNK1-deficient, but not JNK2-deficient mice, had a reduction in inflammatory infiltration and joint damage. This effect was primarily restricted to hematopoetic cells, but B and T cell responses were preserved in mBSA-injected mice. JNK1-deficient macrophages produced cytokines and chemokines comparably to WT counterparts. However, macrophage migration was impaired in vivo and in vitro. Targeting JNK with the peptide inhibitor D-JNKi dramatically reduced inflammation and joint destruction in WT mice. CONCLUSIONS: AIA is dependent on JNK1, but not JNK2. JNK1 is a promising molecular target for reducing autoimmune inflammation as its inhibition impairs macrophage migration. |
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Authors:
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Monica Guma; Lisa M Ronacher; Gary S Firestein; Michael Karin; Maripat Corr |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-1-28 |
Journal Detail:
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Title: Arthritis and rheumatism Volume: - ISSN: 1529-0131 ISO Abbreviation: - Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-2-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0370605 Medline TA: Arthritis Rheum Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 by the American College of Rheumatology. |
Affiliation:
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Laboratory of Gene Regulation and Signal Transduction, Departments, University of California at San Diego, La Jolla, California; Pharmacology, University of California at San Diego, La Jolla, California; Pathology, University of California at San Diego, La Jolla, California. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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