title: Regulation of immune responses by prostaglandin E2.
abstract: PGE(2), an essential homeostatic factor, is also a key mediator of immunopathology in chronic infections and cancer. The impact of PGE(2) reflects the balance between its cyclooxygenase 2-regulated synthesis and 15-hydroxyprostaglandin dehydrogenase-driven degradation and the pattern of expression of PGE(2) receptors. PGE(2) enhances its own production but suppresses acute inflammatory mediators, resulting in its predominance at late/chronic stages of immunity. PGE(2) supports activation of dendritic cells but suppresses their ability to attract naive, memory, and effector T cells. PGE(2) selectively suppresses effector functions of macrophages and neutrophils and the Th1-, CTL-, and NK cell-mediated type 1 immunity, but it promotes Th2, Th17, and regulatory T cell responses. PGE(2) modulates chemokine production, inhibiting the attraction of proinflammatory cells while enhancing local accumulation of regulatory T cells cells and myeloid-derived suppressor cells. Targeting the production, degradation, and responsiveness to PGE(2) provides tools to modulate the patterns of immunity in a wide range of diseases, from autoimmunity to cancer.
authors.affiliation: Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA. kalinskip@upmc.edu
authors.forename: Pawel
authors.initials: P
authors.lastname: Kalinski
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D015232:Dinoprostone / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory / Q000502:physiology*; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism
chemical_list: D018925:Chemokines; D018836:Inflammation Mediators; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone