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

TY - JOUR

T1 - 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

AU - Ropert, Catherine

AU - Almeida, Igor C.

AU - Closel, Meire

AU - Travassos, Luiz R.

AU - Ferguson, Michael A. J.

AU - Cohen, Philip

AU - Gazzinelli, Ricardo T.

PY - 2001/3/1

Y1 - 2001/3/1

N2 - 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.

AB - 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.

M3 - Article

SN - 0022-1767

VL - 166

SP - 3423

EP - 3431

JO - Journal of Immunology

JF - Journal of Immunology

IS - 5

ER -