Abstract

The overall aims of this research are to study the mechanisms of murine arthritis induced by M. arthritidis and to apply this knowledge to further understand the etiology and immunological dysfunction of human rehumatoid arthritis. More specifically investigations will include: 1. The mechanisms of mouse disease induced by M. arthritidis in respect to the role of mitogens in toxic death and acute and chronic arthritis induced by this organism. Studies to determine the immunological abnormalities induced by the administration of mitogens. 2. The genetic control of mouse and rat arthritis and its relationship to background or genes of the major histocompatibility comples. Multiple inbred, congenic and recombinant animal strains will be used. 3. To determine the relationship between Ir gene control of muring lymphocyte activation and the role of HLA.DR antigens in predisposing to human reheumatoid arthritis. 4. To isolate an agent from human rheumatoid tissues utilizing latest methodology. These studies have considerable implications for human disease since the arthritogenic mycoplasmas exhibit inflammatory pathways similar to those demonstrated in human RA. Moreover the new studies provide a link to further understanding the nature of HLA.DR associations with rheumatic disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR002255-28
Application #
3154643
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1978-03-01
Project End
1987-06-30
Budget Start
1986-03-01
Budget End
1987-06-30
Support Year
28
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of Utah
Department
Type
Schools of Medicine
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112

  Publications

Mu, Hong-Hua; Hasebe, Akira; Van Schelt, Adam et al. (2011) Novel interactions of a microbial superantigen with TLR2 and TLR4 differentially regulate IL-17 and Th17-associated cytokines. Cell Microbiol 13:374-87
Hasebe, Akira; Mu, Hong-Hua; Washburn, Leigh R et al. (2007) Inflammatory lipoproteins purified from a toxigenic and arthritogenic strain of Mycoplasma arthritidis are dependent on Toll-like receptor 2 and CD14. Infect Immun 75:1820-6
Mu, Hong-Hua; Humphreys, Jennifer; Chan, Fok Vun et al. (2006) TLR2 and TLR4 differentially regulate B7-1 resulting in distinct cytokine responses to the mycoplasma superantigen MAM as well as to disease induced by Mycoplasma arthritidis. Cell Microbiol 8:414-26
Hasebe, Akira; Pennock, Nathan D; Mu, Hong-Hua et al. (2006) A microbial TLR2 agonist imparts macrophage-activating ability to apolipoprotein A-1. J Immunol 177:4826-32
Cole, Barry C; Mu, Hong-Hua; Pennock, Nathan D et al. (2005) Isolation and partial purification of macrophage- and dendritic cell-activating components from Mycoplasma arthritidis: association with organism virulence and involvement with Toll-like receptor 2. Infect Immun 73:6039-47
Mu, H-H; Pennock, N D; Humphreys, J et al. (2005) Engagement of Toll-like receptors by mycoplasmal superantigen: downregulation of TLR2 by MAM/TLR4 interaction. Cell Microbiol 7:789-97
Mu, H H; Sawitzke, A D; Cole, B C (2001) Presence of Lps(d) mutation influences cytokine regulation in vivo by the Mycoplasma arthritidis mitogen superantigen and lethal toxicity in mice infected with M. arthritidis. Infect Immun 69:3837-44
Sawitzke, A; Joyner, D; Knudtson, K et al. (2000) Anti-MAM antibodies in rheumatic disease: evidence for a MAM-like superantigen in rheumatoid arthritis? J Rheumatol 27:358-64
Mu, H H; Sawitzke, A D; Cole, B C (2000) Modulation of cytokine profiles by the Mycoplasma superantigen Mycoplasma arthritidis mitogen parallels susceptibility to arthritis induced by M. arthritidis. Infect Immun 68:1142-9
Cole, B C (1999) Mycoplasma-induced arthritis in animals: relevance to understanding the etiologies of the human rheumatic diseases. Rev Rhum Engl Ed 66:45S-49S

Showing the most recent 10 out of 22 publications