interleukin-8 and 3-5-dimethyl-2-(3-pyridyl)thiazolidin-4-one

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.

Topics: Aluminum; Basophils; Calcimycin; Calcium; Depression, Chemical; Gene Expression Regulation; GTP-Binding Proteins; Humans; Interleukin-8; Ionophores; Leukocytes, Mononuclear; Leukotriene B4; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Platelet Activating Factor; Platelet Membrane Glycoproteins; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Signal Transduction; Sodium Fluoride; Thiazoles; Thiazolidines