The promoting effect of epinephrine on lipopolysaccharide-induced interleukin-8 production in whole blood may be mediated by thromboxane A2.
Epinephrine is known to enhance lipopolysaccharide (LPS)-induced interleukin (IL)-8 secretion in a platelet dependent manner. To determine whether thromboxane A2 (TxA2; a product from activated platelets) is involved in this process, blood samples drawn either before or 2 h after oral administration of 440 mg acetylsalicylic acid (ASA) were stimulated with LPS (5 ng mL(-1)) and different concentrations of epinephrine were added (0.1-100.0 micromol L(-1)). ASA ingestion significantly (global P < 0.05) reduced the enhancing effect of epinephrine on LPS-induced IL-8 release by 15-28%. To further explore whether TxA2 may be involved in this process, a TxA2 agonist (U46619) was added to whole blood together with LPS instead of epinephrine. U46619 mimicked the epinephrine effect: 20 ng mL(-1) U46619 enhanced LPS-induced IL-8 release by 39% (P < 0.05). Furthermore, preincubation of whole blood with 75 micro mol L-1 or 150 micromol L(-1) SQ29548, a TxA2 receptor antagonist, completely blocked epinephrine's promoting effect on LPS-induced IL-8 release. Since thrombin-activated platelets have been reported to be important in the production of IL-8 in monocytes through the activation of monocytes by exposed RANTES in a P-selectin-dependent reaction, we suggest that the epinephrine effect is mediated by enhanced TxA2 production and subsequent rise in the exposure of RANTES and P-selectin on the platelets of whole blood.
Lund
T
T
Department of Biochemistry, Institute of Medical Biology, Faculty of Medicine, University of Tromsø, Norway.
Østerud
B
B
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D013928:Thromboxane A2 / Q000819:agonists / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D016209:Interleukin-8; D008070:Lipopolysaccharides; D017482:Receptors, Thromboxane; D014409:Tumor Necrosis Factor-alpha; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045749:SQ 29548; D001241:Aspirin; D004837:Epinephrine