Activation of extracellular signal-regulated kinase (ERK)1/2, but not p38 and c-Jun N-terminal kinase, is involved in signaling of a novel cytokine, ML-1.
A novel cytokine, ML-1, was recently discovered, which shares a similar sequence homology with, but is functionally distinct from, IL-17 (Kawaguchi, M., Onuchic, L., Li, X. D., Essayan, D. M., Schroeder, J., Xiao, H. Q., Liu, M. C., Krishnaswamy, G., Germino, G., and Huang, S. K. (2001) J. Immunol. 167, 4430-4435). To determine the signaling mechanisms of ML-1, we investigated activation of mitogen-activated protein (MAP) kinases induced by ML-1. Results show that ML-1 induces in a time-dependent fashion the expression of IL-6 and IL-8 in both primary bronchial epithelial cells (PBECs) and human umbilical vein endothelial cells (HUVECs). ML-1 activated a MAP kinase and an extracellular signal-regulated kinase (ERK)1/2 but not p38 or the c-Jun N-terminal kinase (JNK) in both cell types. Selective MAP kinase kinase (MEK)1/2 inhibitors, PD98059 and U0126, inhibited, in a dose-dependent manner, ML-1-induced expression of IL-6 and IL-8. These findings suggest that ML-1-induced IL-6 and IL-8 production is mediated through the activation of ERK1/2 in both cell types.
Kawaguchi
Mio
M
Johns Hopkins Asthma and Allergy Center and Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, USA.
Onuchic
Luiz F
LF
Huang
Shau-Ku
SK
D000818:Animals; D001980:Bronchi / Q000502:physiology; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D016207:Cytokines / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D020381:Interleukin-17; D015850:Interleukin-6 / Q000494:pharmacology; D016209:Interleukin-8 / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection; D014471:Umbilical Veins; D048051:p38 Mitogen-Activated Protein Kinases
D016207:Cytokines; D004791:Enzyme Inhibitors; D005419:Flavonoids; C440021:IL17F protein, human; D020381:Interleukin-17; D015850:Interleukin-6; D016209:Interleukin-8; D011994:Recombinant Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one