Analysis of the prolongation of rat eosinophil survival induced by recombinant rat interleukin-5.
Rat eosinophil survival was prolonged by recombinant rat IL-5 prepared by the baculovirus expression system. The IL-5-induced prolongation of eosinophil survival was dose-dependently inhibited by the protein synthesis inhibitor cycloheximide, the DNA-dependent RNA synthesis inhibitor actinomycin D, and the tyrosine kinase inhibitor herbimycin A. The MEK-1 inhibitor PD98059 inhibited IL-5-induced phosphorylation of both p44 and p42 MAP kinases, but the IL-5-induced prolongation of eosinophil survival was not inhibited. In contrast, the JAK2 inhibitor AG490 inhibited the IL-5-induced prolongation of eosinophil survival. Treatment of eosinophils with IL-5 resulted in phosphorylation of STAT5 but not STAT1, and the IL-5-induced phosphorylation of STAT5 was inhibited by AG490. These findings suggest that recombinant rat IL-5 activates JAK2 tyrosine kinase, which phosphorylates STAT5, and induces protein synthesis required for the prolongation of rat eosinophil survival.
Ishihara
K
K
Department of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
Satoh
I
I
Ohuchi
K
K
D000818:Animals; D016227:Benzoquinones; D002470:Cell Survival / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000502:physiology; D003609:Dactinomycin / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects* / Q000502:physiology; D015848:Interleukin-5 / Q000494:pharmacology*; D053614:Janus Kinase 2; D047029:Lactams, Macrocyclic; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000502:physiology
D016227:Benzoquinones; D004268:DNA-Binding Proteins; D015848:Interleukin-5; D047029:Lactams, Macrocyclic; D011518:Proto-Oncogene Proteins; D011809:Quinones; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; C494081:Stat1 protein, rat; D015534:Trans-Activators; D003609:Dactinomycin; D017828:Rifabutin; C020754:herbimycin; D003513:Cycloheximide; D011505:Protein-Tyrosine Kinases; C507927:Jak2 protein, rat; D053614:Janus Kinase 2; D019950:Mitogen-Activated Protein Kinase 1