title: The regulation of ICAM-1 and LFA-1 interaction by autacoids and statins: a novel strategy for controlling inflammation and immune responses.
abstract: Histamine, prostaglandin E(2), and catecholamines have been demonstrated to regulate the innate and acquired immune responses. In this review, we describe one of the mechanisms common to the action of these agonists; the regulation of the expression of costimulatory adhesion molecules such as ICAM-1 and B7 antigens on monocytes/macrophages. The specific receptor subtypes involved in the action of each agonist were H(2) for histamine, EP(2)/EP(4) for prostaglandin E(2), and beta(2) for catecholamines, all of which are coupled with adenylate cyclase via Gs protein. The regulation of the expression of adhesion molecules by these agonists in turn leads to the modulation of subsequent cytokine production mediated by cell-cell interaction under different stimuli. Histamine is synthesized in monocytes and T cells by the induction of histidine decarboxylase. The inducible histamine has different dynamics from that in storage granules of mast cells and basophils. Also, noradrenaline appears to be synthesized in lymphocytes. Thus, immune cells can produce histamine, prostaglandins, and noradrenaline by themselves and modulate the cell-cell interaction between monocytes and other cells. Some of the inhibitors of HMG-CoA reductase were shown to bind to the ICAM-1-binding domain of LFA-1, reducing the interaction mediated by ICAM-1/LFA-1. The regulation of interaction mediated by adhesion molecules may provide a new target for controlling inflammatory and immune responses.
authors.affiliation: Department of Pharmacology, Okayama University Graduate School of Medicine and Dentistry, Japan. mbori@md.okayama-u.ac.jp
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nishibori
authors.forename: Hideo K
authors.initials: HK
authors.lastname: Takahashi
authors.forename: Shuji
authors.initials: S
authors.lastname: Mori
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D012898:Autacoids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007109:Immunity / Q000502:physiology*; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D012898:Autacoids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1