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

    92 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

    Glycosylphosphatidylinositols
    Mucins
    Mitogen-Activated Protein Kinases
    Lipopolysaccharides
    Macrophages
    Phosphorylation
    Cytokines
    Mitogen-Activated Protein Kinase 11
    Phosphotransferases
    MAP Kinase Kinase Kinase 4
    MAP Kinase Kinase 4
    CD14 Antigens
    MAP Kinase Kinase Kinases
    Cyclic AMP Response Element-Binding Protein
    Glycoconjugates
    Trypanosoma cruzi
    p38 Mitogen-Activated Protein Kinases
    Interleukin-12
    Glycoproteins
    Transcription Factors

    Cite this

    @article{4a0083f23055480f86c016f2a58ff88d,
    title = "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",
    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.",
    author = "C. Ropert and Almeida, {I. C.} and M. Closel and Travassos, {L. R.} and Ferguson, {M. A.J.} and P. Cohen and Gazzinelli, {R. T.}",
    year = "2001",
    month = "3",
    day = "1",
    doi = "10.4049/jimmunol.166.5.3423",
    language = "English",
    volume = "166",
    pages = "3423--3431",
    journal = "Journal of Immunology",
    issn = "0022-1767",
    publisher = "American Association of Immunologists",
    number = "5",

    }

    TY - JOUR

    T1 - 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

    AU - Ropert, C.

    AU - Almeida, I. C.

    AU - Closel, M.

    AU - Travassos, L. R.

    AU - Ferguson, M. A.J.

    AU - Cohen, P.

    AU - Gazzinelli, R. T.

    PY - 2001/3/1

    Y1 - 2001/3/1

    N2 - 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.

    AB - 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.

    UR - http://www.scopus.com/inward/record.url?scp=0035284834&partnerID=8YFLogxK

    U2 - 10.4049/jimmunol.166.5.3423

    DO - 10.4049/jimmunol.166.5.3423

    M3 - Article

    VL - 166

    SP - 3423

    EP - 3431

    JO - Journal of Immunology

    JF - Journal of Immunology

    SN - 0022-1767

    IS - 5

    ER -