Requirement of mitogen-activated protein kinases and I kappa B phosphorylation for induction of proinflammatory cytokines synthesis by macrophages indicates functional similarity of receptors triggered by glycosylphosphatidylinositol anchors from parasitic protozoa and bacterial lipopolysaccharide

Catherine Ropert, Igor C. Almeida, Meire Closel, Luiz R. Travassos, Michael A. J. Ferguson, Philip Cohen, Ricardo T. Gazzinelli

    Research output: Contribution to journalArticle

    Abstract

    present study, we evaluated the ability of GPI-anchored mucin-like glycoproteins purified from Trypanosoma cruzi trypomastigotes (tGPI-mucin) to trigger phosphorylation of different mitogen-activated protein kinases (MAPKs) and related transcription factors in inflammatory macrophages. Kinetic experiments show that the peak of extracellular signal-related kinase (ERK)-1/ERK-2, stress-activated protein kinase (SAPK) kinase-1/mitogen-activated protein kinase (MAPK) kinase-4, and p38/SAPK-2, phosphorylation occurs between 15 and 30 min after macrophage stimulation with tGPI-mucin or GPI anchors highly purified from tGPI-mucins (tGPT), The use of the specific inhibitors of ERK-1/ERK-2 (PD 98059) and p38/SAPK-2 (SB 203580) phosphorylation also indicates the role of MAPKs, with possible involvement of cAMP response element binding protein, in triggering TNF-alpha and IL-12 synthesis by IFN-gamma -primed-macrophages exposed to tGPI or tGPI-mucin, In addition, tGPI-mucin and tGPI were able to induce phosphorylation of I kappaB, and the use of SN50 peptide, an inhibitor of NF-kappaB translocation, resulted in 70% of TNF-alpha synthesis by macrophages exposed to tGPI-mucin, Finally, the similarity of patterns of MAPK and I kappaB phosphorylation, the concentration of drugs required to inhibit cytokine synthesis, as well as cross-tolerization exhibited by macrophages exposed to tGPI, tGPI-mucin, or bacterial LPS, suggest that receptors with the same functional properties are triggered by these different microbial glycoconjugates.

    Original languageEnglish
    Pages (from-to)3423-3431
    Number of pages9
    JournalJournal of Immunology
    Volume166
    Issue number5
    Publication statusPublished - 1 Mar 2001

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