ABSTRACT
AIM: To assess influence of toll-like receptors (TLR) ligands on the production of proinflammatory cytokine (TNFalpha) by peripheral blood mononuclear cells in patients with acute myocardial infarction (AMI). MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMC) obtained from 13 patients with AMI on 1st and 14th day and from 17 healthy donors were stimulated by peptidoglycan, poly(I:C), lypopolysacchide, zimozan, flagellin and CpG oligodeoxynucleotides, which are ligands of TLR1/2, TLR3, TLR4, TLR2/6, TLR5 and TLR9 respectively. Spontaneous and induced by ligands production of TNFalpha was evaluated in supernatants of PBMC. RESULTS: Increased spontaneous production of TNFalpha by PBMC in patients with AIM was revealed on 1st day of the disease. Ligands of TLR2/6 and TLR4 demonstrated marked stimulatory effect on the production of TNFalpha by PBMC in patients with AMI compared with group of healthy subjects. CONCLUSION: Increased production of TNFalpha by PBMC in patients with AMI indicates the activation of TLR2 and TLR4 on PBMC. Hyperactivation of TLRs during acute pathologic conditions results in excessive production of proinflammatory cytokines, specifically TNFalpha, and can induce damage of cells and tissues involved in acute pathologic process.
Subject(s)
Myocardial Infarction/immunology , Toll-Like Receptor 2/immunology , Toll-Like Receptor 4/immunology , Tumor Necrosis Factor-alpha/immunology , Aged , Aged, 80 and over , Cells, Cultured , Female , Flagellin/immunology , Flagellin/pharmacology , Humans , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Ligands , Lipopolysaccharides/immunology , Lipopolysaccharides/pharmacology , Male , Middle Aged , Peptidoglycan/immunology , Peptidoglycan/pharmacology , Poly I-C/immunology , Poly I-C/pharmacology , Toll-Like Receptor 2/agonists , Toll-Like Receptor 4/agonists , Tumor Necrosis Factor-alpha/biosynthesis , Zymosan/immunology , Zymosan/pharmacologyABSTRACT
Production of citokines of tumor-necrosis factor (TNF)-alpha and interferon (IFN)-alpha by peripheral blood mononuclear cells (PBMC) from healthy men and from patients with common variable immunodeficiency (CVID) after stimulation with zymosan, lypopolysaccharides, flagellin and CpG, which are ligands of TLR 2/6, TLR 4, TLR 5, TLR 9 respectively, was studied in vitro. In healthy men production of TNF-alpha varied between individuals, whereas synthesis of IFN-alpha was similar. Spontaneous production of TNF-alpha by PBMC in patients with CVID was increased and accompanied by decrease in TNF-alpha production stimulated by each analyzed ligands except CpG. Observed changes in TLR-dependent TNF-alpha production can play important role in pathogenesis of CVID.
Subject(s)
Common Variable Immunodeficiency/immunology , Cytokines/biosynthesis , Immunocompetence/immunology , Toll-Like Receptors/immunology , Adolescent , Adult , Cells, Cultured , Child , Female , Humans , Interferon-alpha/biosynthesis , Leukocytes, Mononuclear/immunology , Ligands , Male , Tumor Necrosis Factor-alpha/biosynthesisABSTRACT
The production of TNF-alpha and IFN-alpha cytokines by peripheral blood mononuclears in response to stimulation by TLR2/6, TLR4, TLR5, TLR9 ligands (zymosan, LPS, flagellin, and CpG-oligodeoxynucleotide, respectively) was studied in donors and patients with common variable immunodeficiency. Individual characteristics of TNF-alpha production by mononuclears were revealed in donors. Reduced stimulated production of TNF-alpha in response to stimulation with TLR4 and TLR5 ligands in vitro was detected in patients with common variable immunodeficiency.
Subject(s)
Blood Donors , Common Variable Immunodeficiency/physiopathology , Interferon-alpha/biosynthesis , Toll-Like Receptors/physiology , Tumor Necrosis Factor-alpha/biosynthesis , Adolescent , Adult , Child , Common Variable Immunodeficiency/blood , Female , Flagellin/pharmacology , Humans , Leukocytes, Mononuclear , Lipopolysaccharides/pharmacology , Male , Oligodeoxyribonucleotides/pharmacology , Poly I-C/pharmacology , Toll-Like Receptors/drug effects , Zymosan/pharmacologyABSTRACT
This review deals with rapidly accumulating information on a highly important components of the congenital immune system: Toll-like receptors playing a leading role in the recognition of microbial patterns. The data on the main structural and functional features of Toll-like receptors and their distribution in the body are summarized. The main signal paths are characterized and the key molecules which take part in the transduction are pointed out. Special attention is paid to the activating action of lipopolysaccharides through TLR4. Pathological processes developing as the result of damages in the structure and function of Toll-like receptors in humans and experimental animals are determined.
