Journal of Pharmacological Sciences
Online ISSN : 1347-8648
Print ISSN : 1347-8613
ISSN-L : 1347-8613
Current Perspectives
The Regulation of ICAM-1 and LFA-1 Interaction by Autacoids and Statins: a Novel Strategy for Controlling Inflammation and Immune Responses
Masahiro NishiboriHideo K. TakahashiShuji Mori
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2003 Volume 92 Issue 1 Pages 7-12


Histamine, prostaglandin E2, 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 H2 for histamine, EP2/EP4 for prostaglandin E2, and β2 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.

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© The Japanese Pharmacological Society 2003
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