Interleukin (IL)-8-induced in vitro human lymphocyte migration is inhibited by cholera and pertussis toxins and inhibitors of protein kinase C.
To further investigate the intracellular mechanisms involved in IL-8-induced human mixed peripheral blood lymphocyte (PBL) migration, the effects of pertussis toxin (PTX), cholera toxin (CTX), and protein kinase C (pkC) inhibitors were investigated. Potent inhibition of IL-8-induced PBL migration was observed following exposure of PBL to PTX and CTX (1 pM to 0.1 microM), 8-bromo cyclic adenosine monophosphate (cAMP; 1 nM to 1 microM), H7 (1 pM to 0.1 microM), sphingosine (0.1 microM to 100 microM) and the novel pkC inhibitors Ro 31-7549 and Ro 31-8220 (10 pM to 1 microM) for 10 min. Following incubation of the lymphocytes for 30 min in the presence of the direct activators of pkC, 1-oleoyl-2-acetyl-sn-glycerol (OAG) and 1,2-dioctanoyl-sn-glycerol (DOG; 10nM to 100 microM), there was a reversal of the effects of a suboptimal dose of the specific pkC inhibitors Ro 31-7549 and Ro 31-8220. These results suggest that intracellular signals transduced during IL-8-induced in vitro PBL migration may involve pertussis and cholera toxin-sensitive G protein subunits and activation of pkC, processes which are characteristically linked to receptor binding.
Bacon
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KB
Institute of Dermatology, St. Thomas's Hospital, London, England, U.K.
Camp
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D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002465:Cell Movement / Q000187:drug effects; D002630:Chemotactic Factors / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002772:Cholera Toxin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles; D016209:Interleukin-8; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D008214:Lymphocytes / Q000502:physiology*; D008301:Maleimides; D037342:Pertussis Toxin; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013110:Sphingosine / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D002630:Chemotactic Factors; D004075:Diglycerides; D007211:Indoles; D016209:Interleukin-8; D007378:Interleukins; D007546:Isoquinolines; D008301:Maleimides; D010879:Piperazines; D010566:Virulence Factors, Bordetella; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002772:Cholera Toxin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D013110:Sphingosine; C064758:Ro 31-8220; C064755:Ro 31-7549