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

C. Ropert, I. C. Almeida, M. Closel, L. R. Travassos, M. A.J. Ferguson, P. Cohen, R. T. Gazzinelli

    Research output: Contribution to journalArticle

    96 Citations (Scopus)

    Abstract

    In the 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 (tGPI). 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-α and IL-12 synthesis by IFN-γ-primed-macrophages exposed to tGPI or tGPI-mucin. In addition, tGPI-mucin and tGPI were able to induce phosphorylation of IκB, and the use of SN50 peptide, an inhibitor of NF-κB translocation, resulted in 70% of TNF-α synthesis by macrophages exposed to tGPI-mucin. Finally, the similarity of patterns of MAPK and IκB 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
    DOIs
    Publication statusPublished - 1 Mar 2001

    Fingerprint Dive into the research topics of 'Requirement of mitogen-activated protein kinases and IκB phosphorylation for induction of proinflammatory cytokines synthesis by macrophages indicates functional similarity of receptors triggered by glycosylphosphatidylinositol anchors from parasitic protozoa and bacterial lipopolysaccharide'. Together they form a unique fingerprint.

  • Cite this