| Role of adrenomedullin in Lyme disease. | |
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MedLine Citation:
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PMID: 20921145 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Borrelia burgdorferi stimulates a strong inflammatory response during infection of a mammalian host. To understand the mechanisms of immune regulation employed by the host to control this inflammatory response, we focused our studies on adrenomedullin, a peptide produced in response to bacterial stimuli that exhibits antimicrobial activity and regulates inflammatory responses by modulating the expression of inflammatory cytokines. Specifically, we investigated the effect of B. burgdorferi on the expression of adrenomedullin as well as the ability of adrenomedullin to dampen host inflammatory responses to the spirochete. The concentration of adrenomedullin in the synovial fluid of untreated Lyme arthritis patients was elevated compared with that in control osteoarthritis patient samples. In addition, coculture with B. burgdorferi significantly increased the expression of adrenomedullin in RAW264.7 macrophages through MyD88-, phosphatidylinositol 3-kinase (PI3-K)-, and p38-dependent signaling cascades. Furthermore, the addition of exogenous adrenomedullin to B. burgdorferi-stimulated RAW264.7 macrophages resulted in a significant decrease in the induction of proinflammatory cytokines. Taken together, these results suggest that B. burgdorferi increases the production of adrenomedullin, which in turn negatively regulates the B. burgdorferi-stimulated inflammatory response. |
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Authors:
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Meghan L Marre; Courtney T Darcy; Janeth Yinh; Shizuo Akira; Satoshi Uematsu; Allen C Steere; Linden T Hu |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-10-04 |
Journal Detail:
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Title: Infection and immunity Volume: 78 ISSN: 1098-5522 ISO Abbreviation: Infect. Immun. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-16 Completed Date: 2010-12-15 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 0246127 Medline TA: Infect Immun Country: United States |
Other Details:
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Languages: eng Pagination: 5307-13 Citation Subset: IM |
Affiliation:
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Graduate Program in Immunology, Sackler School of Graduate Biomedical Sciences, Tufts University, 155 Harrison Avenue, Boston, Massachusetts 02111, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adrenomedullin
/
analysis,
biosynthesis,
immunology,
physiology* Animals Borrelia burgdorferi / immunology Case-Control Studies Cell Line Chemokine CXCL2 / immunology Humans Inflammation / immunology, physiopathology Interleukin-1beta / immunology Interleukin-6 / immunology Lyme Disease / immunology*, physiopathology Macrophages / immunology, physiology Mice Mice, Inbred C57BL Osteoarthritis / immunology, physiopathology Reverse Transcriptase Polymerase Chain Reaction Synovial Fluid / chemistry Tumor Necrosis Factor-alpha / immunology |
| Grant Support | |
ID/Acronym/Agency:
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R01-AI-50043/AI/NIAID NIH HHS; R56AI80846/AI/NIAID NIH HHS; T32 AI07077/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chemokine CXCL2; 0/Interleukin-1beta; 0/Interleukin-6; 0/Tumor Necrosis Factor-alpha; 148498-78-6/Adrenomedullin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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