Research interest: Immunobiology of Epithelial Cell Injury Our laboratory is interested in the role of T lymphocytes in epithelial cell injury and mechanisms for damage to the intestinal mucosa during inflammation. We use in vitro models of epithelial cells and gut-derived mononuclear cells as well as animal models with induced inflammatory injury to determine pathways by which T lymphocytes and their secreted cytokines induce and suppress tissue-destructive immune responses. Currently, our research is focused on two areas: The first is how cytokines from immune and other cells affect epithelial cell function, particularly tight junction function, permeability by macromolecules, cytoarchitecture, and early gene activation. IFN-g and TGF-b1 have been at the center of these studies, as we investigate the process by which these cytokines are released, bind to specific receptors at particular locations on polarized cells, and cause changes in the target organ. These studies rely on techniques of recombinant generation of interleukins, cell sorting, and electrophysiology. A second area of interest is understanding how inflammation in a mucosa-bearing organ (such as the gastrointestinal tract, bronchorespiratory tree and genitourinary tract) is up- and down-regulated. We are interested in how different subsets of CD4+ lymphocytes (Th 1 and Th 2 cells, for example) aid and/or retard tissue destructive inflammation; how neuropeptides and PGE2 may dampen unwanted immune responses; and strategies used by the host to preserve self-tissue. Studies are carried out in inbred rat strains, using recombinantly produced cytokines and detailed morphologic analysis of target cells. Dr. Roche is also a member of the Beirne B. Carter Center for Immunology Research. Selected Publications: Planchon S, Fiocchi C, Thompson C, Roche JK. Transforming Growth Factor-b1 Preserves Epithelial Barrier Function: Identification of Receptors, Biochemical Intermediates, and Cytokine Antagonists. J Cell Physiol 181:55-66, 1999. Cosme R, Lublin D, Takafuji V, Lynch K, Rocke JK. Prostaniods in human colonic mucosa: effects of inflammation on PGE2 receptor expression. Human Immunology 61:684-969, 2000. Martins CAP, Guerrant RL, Cosme R, Fayer R, Roche JK. TGF-b amelinates intestinal epithelial barrier disruption by C. Parvum in vitro in the absence of mucosal T lymphocytes. Infect. Immunity 68:5635-5644, 2000. McCarn K, Yursik B, Halim S, Roche JK. Peri-epithelial origin of prostanoids in the human colon. J Cell Physiol 194:176-183, 2003.
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