Research in this program is focused on the basic mechanisms by which the host mobilizes and modulates cellular inflammatory reactions in defense against foreign antigens and infectious agents. In a multi-disciplinary approach, mechanisms of integrin adhesion, chemotaxis, signaling, mediator synthesis and apoptosis are explored in vitro and extended into experimental animal models (bacterial induced rodent arthritis; knockout and transgenic mice) for in vivo analysis. In addition, human conditions of chronic inflammatory disease in response to foreign implants, infectious pathogens, or of unknown etiology are explored at the cellular, molecular and biochemical levels. Understanding the mechanisms which control normal immune cell recruitment, activation and/or deletion and the switch to pathogenesis underlies the development of strategies for modulating chronic pathogenic inflammatory diseases. In an experimental model of arthritis, we have characterized the immunopathology through phenotypic, functional and morphologic parameters, in addition to DNA microarrays and ribonuclease protection assays, to identify targets for therapeutic intervention including leukocyte adhesion, signal transduction, cytokines, proteases, and nitric oxide. We recently demonstrated that human chorionic gonadotropin, a hormone that increases in pregnancy and declines sharply thereafter, was an effective inhibitor of experimental arthritis. Systemic delivery of hCG inhibited cytokines and NO, but increased immunosuppressive TGF-beta. These findings demonstrate unique immunoregulatory properties of hCG and provide insight into a potential mechanism whereby remission of RA symptoms occurs during pregnancy. In related studies, new insights into the regulation of immune function through TGF-beta, including TGF-beta-mediated apoptotic pathways in T lymphocytes, raise the prospect of novel approaches to controlling immunological tolerance.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Intramural Research (Z01)
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Dental & Craniofacial Research
United States
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