Effects of various drugs (staurosporine, herbimycin A, ketotifen, theophylline, FK506 and cyclosporin A) on eosinophil viability.
Eosinophils are known to play an important role in the pathogenesis of asthma and other allergic diseases. This study demonstrated the effects of various drugs on eosinophil viability in vitro, which might help clinicians and researchers in treating and studying eosinophilic diseases. Staurosporine, a protein kinase C inhibitor, and herbimycin A, a tyrosine kinase inhibitor, at 10(-6) M and 10(-7) M significantly lowered eosinophil viability in a dose-dependent fashion (p < 0.002, p < 0.02 and p < 0.001, p < 0.002, respectively). Both staurosporine and herbimycin A reduced eosinophil survival in a time-dependent fashion at 10(-6) M and 10(-7) M. Ketotifen at 10(-4) M and theophylline at 10(-3) M, significantly decreased eosinophil viability (p < 0.001 and p < 0.001, respectively) in the presence of 100 pg/ml of recombinant human interleukin-5 (rhIL-5). Both FK506 and cyclosporin A at 10(-4) M significantly reduced eosinophil viability (p < 0.001 and p < 0.005, respectively) in the presence of 100 pg/ml of rhIL-5. Our data show that ketotifen, theophylline, FK506, cyclosporin A reduced eosinophil viability at a high concentration. Furthermore, it is suggested that protein kinase C and tyrosine kinase are involved in eosinophil survival.
Hossain
M
M
First Department of Internal Medicine, Shinshu University School of Medicine.
Okubo
Y
Y
Sekiguchi
M
M
D000470:Alkaloids / Q000494:pharmacology*; D001249:Asthma / Q000097:blood; D016227:Benzoquinones; D002470:Cell Survival / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D004804:Eosinophils / Q000187:drug effects*; D006801:Humans; D007665:Ketotifen / Q000494:pharmacology*; D047029:Lactams, Macrocyclic; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology*; D017828:Rifabutin / Q000031:analogs & derivatives; D019311:Staurosporine; D016559:Tacrolimus / Q000494:pharmacology*; D013806:Theophylline / Q000494:pharmacology*
D000470:Alkaloids; D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D011809:Quinones; D017828:Rifabutin; C020754:herbimycin; D016572:Cyclosporine; D013806:Theophylline; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D019311:Staurosporine; D016559:Tacrolimus; D007665:Ketotifen