PAF-induced RANTES production by human airway smooth muscle cells requires both p38 MAP kinase and Erk.
Airway smooth muscle (ASM) cells, which have been regarded as having contractile properties in response to contractile inflammatory mediators, may also participate in airway inflammatory response by expressing various cytokines, including RANTES. However, the intracellular signal that regulates cytokine expression in ASM cells has not been determined. In the present study, we examined the role of p38 mitogen-activated protein (MAP) kinase and extracellular signal-regulated kinase (Erk) in RANTES production by ASM cells stimulated by platelet-activating factor (PAF) and tumor necrosis factor (TNF)-alpha. The results showed that PAF induced the threonine and tyrosine phosphorylation of p38 MAP kinase and Erk, and p38 MAP kinase and Erk activity. SB 203580 and PD 98059 almost completely inhibited p38 MAP kinase and Erk activity, respectively. SB 203580 and PD 98059 partially inhibited and acted additively to inhibit PAF-induced RANTES production. PAF also induced c-Jun-NH(2)-terminal kinase ( JNK) phosphorylation. TNF-alpha induced p38 MAP kinase and Erk phosphorylation, but neither SB 203580 nor PD 98059 inhibited RANTES production. These results indicate that both p38 MAP kinase and Erk involve RANTES production by ASM cells stimulated with PAF, but not TNF-alpha, and that the role of p38 MAP kinase and Erk in RANTES production by ASM cells appears to be stimulus-dependent.
Maruoka
S
S
First Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. shuh@med.nihon-u.ac.jp
Hashimoto
S
S
Gon
Y
Y
Takeshita
I
I
Horie
T
T
D001980:Bronchi / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology*; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000378:metabolism*; D004261:DNA Replication / Q000502:physiology; D004790:Enzyme Induction / Q000502:physiology; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D010766:Phosphorylation; D010972:Platelet Activating Factor / Q000502:physiology*; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases
D018946:Chemokine CCL5; D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases