Inhibition of leukotriene formation and IL-8 release by the paf-receptor antagonist SM-12502.
We analyzed the effect of the PAF receptor antagonist (+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride (SM-12502) on the release of leukotriene B4 and IL-8 from human leukocytes. Peripheral blood from healthy donors was separated in two different fractions: polymorphonuclear leukocytes (PMN) and a lymphocyte, monocyte and basophil granulocyte cell fraction (LMB). After incubation of the cell population with different concentrations of SM-12502 the cells were subsequently stimulated with either the Ca ionophore A23187, the bacterial derived peptide fMLP, or with an activator of heterotrimetric G-proteins, the sodium fluoride (NaF, in the presence of Al3+). The PAF receptor antagonist led to a concentration and time dependent inhibition of LTB4 formation and IL-8 release from PMN and LMB. Our data clearly indicate an inhibitory effect of the PAF receptor antagonist SM-12502 on the formation of mediators of the lipoxygenase pathway and on the release of IL-8.
Hilger
R A
RA
Ruhr-Universität Bochum, Germany.
Köller
M
M
König
W
W
D000535:Aluminum / Q000494:pharmacology; D001491:Basophils / Q000187:drug effects* / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D003864:Depression, Chemical; D019204:GTP-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D007476:Ionophores / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D007975:Leukotriene B4 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010972:Platelet Activating Factor / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D015398:Signal Transduction / Q000187:drug effects; D012969:Sodium Fluoride / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines
D016209:Interleukin-8; D007476:Ionophores; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013844:Thiazoles; D053778:Thiazolidines; C039351:platelet activating factor receptor; C065776:3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one; D007975:Leukotriene B4; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D012969:Sodium Fluoride; D000535:Aluminum; D019204:GTP-Binding Proteins; D002118:Calcium