Potent and specific inhibition of IL-8-, IL-1 alpha- and IL-1 beta-induced in vitro human lymphocyte migration by calcium channel antagonists.
The role of calcium in interleukin- (IL) 8-, IL-1 alpha- and IL-1 beta-induced lymphocyte migration has been investigated by using the calcium channel antagonists, verapamil, nifedipine, diltiazem (IL-8) and the optical isomers of the dihydropyridine analogue SDZ 202-791 (IL-8, IL-1 alpha and IL-1 beta). Potent inhibition of IL-8-induced migration was observed in response to nifedipine (IC50 = 10 nM), verapamil (IC50 = 60 nM) and diltiazem (IC50 = 10 nM). The (+)-isomer of SDZ 202-791 was without effect on any of the agonists tested, however, the (-)-isomer induced dose-related inhibition of stimulated migration, IC50 values being 0.1 nM, 10 pM and 1.0 nM, for IL-8-, IL-1 alpha- and IL-1 beta-induced migration, respectively. Reversal of the inhibitory effects of the (-)-isomer was obtained in the presence of increasing concentrations of (+)-isomer. The induction of lymphocyte migration by IL-8, IL-1 alpha and IL-1 beta therefore appears to be a process dependent on calcium channel activation.
Bacon
K B
KB
Institute of Dermatology, United Medical and Dental School of Guy Hospital, London, UK.
Westwick
J
J
Camp
R D
RD
D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002630:Chemotactic Factors / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004095:Dihydropyridines / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D016209:Interleukin-8; D007378:Interleukins / Q000494:pharmacology*; D007700:Kinetics; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002630:Chemotactic Factors; D004095:Dihydropyridines; D007375:Interleukin-1; D016209:Interleukin-8; D007378:Interleukins; D011994:Recombinant Proteins; C045796:SAN 202791; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine