Substance P: A competence factor for human fibroblast proliferation that induces the release of growth‐regulatory arachidonic acid metabolites

Journal of Cellular Physiology - Tập 156 Số 3 - Trang 579-587 - 1993
Christian M. Kähler1, Manfred Herold1, Christian J. Wiedermann1
1Department of Internal Medicine, Faculty of Medicine, University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria

Tóm tắt

AbstractSubstance P (SP) was recognized to stimulate cell growth. The mechanisms of growth control by SP are unknown. We, therefore, investigated mechanisms of the effect of SP on proliferation of human skin fibroblasts. SP did not stimulate proliferation of fibroblasts growth arrested by serum starvation over 48 hours. However, in the presence of acetylsalicylic acid SP potently stimulated fibroblast growth. A bell‐shaped dose‐response curve with maximal stimulation at picomolar concentrations was found. Specificity of the mitogenic effect was analyzed by use of synthetic SP analogs. Only neurokinin‐1 receptor agonists were active, whereas a specific neurokinin‐2 receptor analog did not exhibit mitogenicity. Analyzing the supernatants of growth‐arrested fibroblasts treated with SP indicated that SP provokes release of the arachidonic acid metabolites, prostaglandin E2, and prostacyclin but not thromboxane B2 or leukotriene B4. Since similar response patterns in proliferation and arachidonic acid metabolite release have been described for several proinflammatory cytokines, some of which are known to act as competence factors in proliferation, we characterized the mitogenic effect of SP. Results established that SP stimulates fibroblast growth in a manner typical of competence factors. We conclude that arachidonic acid metabolites are involved in the cell cycle‐dependent mitogenic action of SP on human skin fibroblasts. © 1993 Wiley‐Liss, Inc.

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Journal of Cellular Physiology

Tập 156 Số 3

579-587

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