Human peripheral blood mononuclear cells stimulated by Schistosoma mansoni antigens: association between protein tyrosine kinases, mitogen-activated protein kinases and cytokine production.
Concerning schistosomiasis, little is known about the intracellular signaling response of human peripheral blood mononuclear cells (PBMC) to Schistosoma mansoni antigens. To understand the critical role of protein tyrosine kinases (PTKs) in PBMC activation by S. mansoni antigens, we investigated how inhibition of PTKs by genistein, a tyrosine kinase inhibitor, affects proliferation, cytokine production and activation of mitogen-activated protein kinases (MAPKs). Our studies showed that PTKs have an important role in proliferation of PBMC from chronic schistosomiasis patients as cells stimulated with S. mansoni soluble antigens in the presence of genistein had an impaired proliferation. In contrast, PTK inhibition failed to cause any effect on MAPKs activity. We also evaluated the cytokine production for interleukin (IL)-2, interferon gamma (IFN-gamma), and IL-10 in culture supernatants of PBMC treated with or without PTKs inhibitor. Our results show that PBMC from chronic patients produced a high amount of IL-10 when stimulated with soluble egg antigen preparation (SEA), however, the amount produced of IL-2 and IFN-gamma was not significant. In the presence of PTKs inhibitor only the production of IL-10 was decreased. The findings suggest that PTKs are involved on signal transduction pathway for PBMC activation, but may not be an absolute requirement for all signaling responses to S. mansoni antigens.
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Universidade Federal de Minas Gerais, Departamento de Bioquímica e Imunologia, Cep 30.161-970, caixa postal 486, ICB, Belo Horizonte, MG, Brazil.
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D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D019833:Genistein / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000096:biosynthesis; D016753:Interleukin-10 / Q000032:analysis / Q000096:biosynthesis; D007376:Interleukin-2 / Q000032:analysis / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000276:immunology; D012550:Schistosoma mansoni / Q000276:immunology*; D012552:Schistosomiasis / Q000097:blood / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
D000947:Antigens, Helminth; D004791:Enzyme Inhibitors; D007376:Interleukin-2; D016753:Interleukin-10; D007371:Interferon-gamma; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases