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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Szabó, C. Kuhel, D. G. Haskó, G. Salzman, A. L. |
| Description | Author Affiliation: Haskó G ( Inotek Corp., Suite 419E, 100 Cummings Center, Beverly, Massachusetts, MA 01915, USA.) |
| Abstract | Immune cell activation releases ATP into the extracellular space. ATP-sensitive P2 purinergic receptors are expressed on immune cells and activation of these receptors alters immune cell function. Furthermore, ATP is metabolized by ectonucleotidases to adenosine, which has also been shown to alter cytokine production. In the present study, we investigated how extracellular ATP affects interleukin (IL)-12 and tumour necrosis factor (TNF)-alpha production in bacterial lipopolysaccharide (LPS)-treated murine peritoneal macrophages and we also examined whether extracellular ATP alters the production of the T helper 1 cytokine interferon (IFN)-gamma. Pretreatment of the peritoneal macrophages with ATP or various ATP analogues decreased both IL-12 and TNF-alpha production induced by LPS (10 microgram ml(-1)). The effect of ATP was partially reversed by cotreatment with adenosine deaminase (0.1 - 1 u ml(-1)), suggesting that the suppressive effect of ATP on cytokine production is, in part, due to its degradation products. Immunoneutralization with an anti-IL-10 antibody demonstrated that although ATP increases IL-10 production, the inhibition of IL-12 and TNF-alpha production is independent of the increased IL-10. The effect of ATP was pretranslational, as it suppressed steady state levels of mRNAs for IL-12 (both p35 and p40). In spleen cells stimulated with either LPS (10 microgram ml(-1)) or anti-CD3 (2 microgram ml(-1)) antibody, ATP suppressed, in a concentration-dependent manner, the production of IFN-gamma. These results suggest that extracellular ATP has multiple anti-inflammatory effects and that release of ATP into the extracellular space may play a role in blunting the overactive immune response in autoimmune diseases. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 5 |
| Volume Number | 129 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2000-03-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Adenosine Triphosphate Pharmacology Interleukin-12 Metabolism Macrophages, Peritoneal Tumor Necrosis Factor-alpha Animals Antigens, CD3 Immunology Interferon-gamma Biosynthesis Interleukin-10 Lipopolysaccharides Drug Effects Mice Mice, Inbred BALB C Mitochondria Oxygen Consumption Purinergic P2 Receptor Antagonists RNA Isolation & Purification Ribonucleases Spleen Cytology Research Support, U.S. Gov't, P.H.S. |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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