p38 mitogen-activated protein kinase activation is required for human neutrophil function triggered by TNF-α or FMLP stimulation

You Li Zu, Jiafan Qi, Annette Gilchrist, Gustavo A. Fernandez, Dolores Vazquez-Abad, Donald L. Kreutzer, Chi Kuang Huang, Ramadan I. Sha'afi

Research output: Contribution to journalArticle

310 Scopus citations

Abstract

Mitogen-activated protein (MAP) kinase-mediated signal-transduction pathways convert extracellular stimulation into a variety of cellular functions. However, the roles of MAP kinases in neutrophils are not web understood yet. Protein phosphorylation analysis of cellular MAP kinases indicates that exposure of human neutrophils to chemotactic factor FMLP as well as granulocyte-macrophage CSF, PMA, or ionomycin rapidly induced the activation of p38 and p44/42 MAP kinases, but stimulation with inflammatory cytokine TNF-α triggered the activation of p38 MAP kinase only. To study the cellular functions of these MAP kinases, the inhibitor SB20358, which specifically inhibited enzymatic activity of cellular p38 MAP kinase, and the inhibitor PD98059, which specifically blocked the induced protein phosphorylation and activation of p44/42 MAP kinase in intact neutrophils, were utilized. Inhibition of the cellular p38 MAP kinase activation almost completely abolished the TNF-α-stimulated IL-8 production and superoxide generation of human neutrophils. In addition, the FMLP-induced neutrophil chemotaxis as well as superoxide generation were suppressed markedly by inhibiting the activation of cellular p38 MAP kinase, but not p44/42 MAP kinase. Moreover, RIA indicates that the activation of cellular p38 MAP kinase was required for the neutrophil IL-8 production stimulated by granulocyte-macrophage CSF or LPS as well as TNF-α, but not for that induced by PMA or ionomycin. These results demonstrate that the activation of cellular p38 MAP kinase is indispensable for the TNF-α- or FMLP-mediated cellular functions in human neutrophils, and suggest that p38 MAP kinase may play a different role in response to distinct stimulation.

Original languageEnglish (US)
Pages (from-to)1982-1989
Number of pages8
JournalJournal of Immunology
Volume160
Issue number4
StatePublished - Feb 15 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'p38 mitogen-activated protein kinase activation is required for human neutrophil function triggered by TNF-α or FMLP stimulation'. Together they form a unique fingerprint.

Cite this