MAPK-activated protein kinase-2 participates in p38 MAPK-dependent and ERK-dependent functions in human neutrophils

Patricia Y Coxon; Madhavi J Rane; Silvia Uriarte; David W Powell; Saurabh Singh; Waseem Butt; Qingdan Chen; Kenneth R McLeish

doi:10.1016/s0898-6568(03)00074-3

MAPK-activated protein kinase-2 participates in p38 MAPK-dependent and ERK-dependent functions in human neutrophils

Cell Signal. 2003 Nov;15(11):993-1001. doi: 10.1016/s0898-6568(03)00074-3.

Authors

Patricia Y Coxon¹, Madhavi J Rane, Silvia Uriarte, David W Powell, Saurabh Singh, Waseem Butt, Qingdan Chen, Kenneth R McLeish

Affiliation

¹ Department of Medicine, University of Louisville Health Sciences Center, Louisville, KY 40202, USA.

PMID: 14499342
DOI: 10.1016/s0898-6568(03)00074-3

Abstract

Many neutrophil responses, including chemotaxis, exocytosis, respiratory burst activity and chemokine synthesis, are mediated by p38 MAPK. MAPK-activated protein kinase-2 (MK2) is activated by p38 MAPK in human neutrophils. The present study tested the hypothesis that MK2 mediates multiple p38 MAPK-dependent responses in human neutrophils by comparing the effect of the p38 MAPK inhibitor, SB203580, with an MK2 inhibitory peptide. Both SB203580 and MK2 inhibitory peptide attenuated respiratory burst activity, exocytosis, and chemotaxis. Lipopolysaccharide (LPS)-induced IL-8 production was inhibited by SB203580, but not by the MK2 inhibitory peptide. Inhibition of chemotaxis and respiratory burst activity by SB203580 was less than that of MK2 inhibitory peptide. Inhibition of extracellular signal-regulated kinase (ERK) activity by PD98059 attenuated superoxide release and chemotaxis, and simultaneous treatment with SB203580 and PD98059 demonstrated additive inhibition. ERK phosphorylated MK2 in vitro and activated MK2 in f-methionyl-leucyl-phenylalanine (FMLP)-stimulated neutrophils. These data suggest that MK2 mediates both ERK- and p38 MAPK-dependent neutrophil responses.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Chemotaxis, Leukocyte / physiology
Enzyme Activation / physiology
Enzyme Inhibitors / pharmacology
Exocytosis / physiology
Flavonoids / pharmacology
Humans
Imidazoles / pharmacology
Interleukin-8 / metabolism
Intracellular Signaling Peptides and Proteins
Lipopolysaccharides / metabolism
MAP Kinase Signaling System / physiology
Mitogen-Activated Protein Kinases / metabolism*
N-Formylmethionine Leucyl-Phenylalanine / metabolism
Neutrophil Activation / physiology*
Neutrophils / enzymology*
Phosphorylation
Protein Kinases*
Protein Serine-Threonine Kinases
Pyridines / pharmacology
Respiratory Burst / physiology
Signal Transduction / physiology*
Superoxides / metabolism
p38 Mitogen-Activated Protein Kinases

Substances

Enzyme Inhibitors
Flavonoids
Imidazoles
Interleukin-8
Intracellular Signaling Peptides and Proteins
Lipopolysaccharides
Pyridines
Superoxides
N-Formylmethionine Leucyl-Phenylalanine
Protein Kinases
MAP-kinase-activated kinase 2
Protein Serine-Threonine Kinases
Mitogen-Activated Protein Kinases
p38 Mitogen-Activated Protein Kinases
SB 203580
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one