title: cAMP mediates IL-1-induced lymphocyte penetration through endothelial monolayers.
abstract: Endothelial cell incubated with IL-1 have been shown adhere more lymphocytes than nontreated endothelial cells. Here we demonstrate that IL-1 can also increase lymphocyte penetration through endothelial monolayers in vitro. IL-1 induced a transient increase in the number of lymphocytes penetrated through the endothelial monolayer into a filter in a time- and dose-dependent manner. This effect could be mimicked by increasing the cytosolic cAMP levels in the endothelial cells either by forskolin or dibutyryl-cAMP. Concomitantly we were able to show that IL-1 increased the cytosolic cAMP levels in endothelial cells. An inhibitor of adenylate cyclase, ddAdo, decreased both the IL-1-induced cAMP elevation and lymphocyte penetration. A protein kinase A inhibitor HA 1004 could inhibit the IL-1-induced lymphocyte penetration, where as protein kinase C (N-(2-guamidino-ethyl)-5-isoquinolinesyl foamide hydrocloride) and calcium-calmodulin (N-(6-aminohexyl)-5-chloro-1-naphthalensulfanamide) inhibitors had no effect. Adding dibutyryl-cGMP or calcium ionophore to the endothelial cells could not mimic IL-1-induced penetration and finally IL-1 did not induce PKC translocation in endothelial cells. These data support the view that IL-1 acts via cAMP as a second messenger in regard to lymphocyte penetration through endothelial cells. The above data demonstrate that IL-1-induced lymphocyte penetration through endothelial cells and that this IL-1-induced signal is transduced via cAMP in endothelial cells.
authors.affiliation: Transplantation Laboratory, University of Helsinki, Finland.
authors.forename: J P
authors.initials: JP
authors.lastname: Turunen
authors.forename: P
authors.initials: P
authors.lastname: Mattila
authors.forename: R
authors.initials: R
authors.lastname: Renkonen
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D002118:Calcium / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D006152:Cyclic GMP / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology*; D015870:Gene Expression / Q000187:drug effects; D066298:In Vitro Techniques; D007249:Inflammation / Q000503:physiopathology; D007375:Interleukin-1 / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D007375:Interleukin-1; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D003609:Dactinomycin; D005576:Colforsin; C017967:W 7; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D003513:Cycloheximide; D000242:Cyclic AMP; D011493:Protein Kinase C; D006152:Cyclic GMP; D002118:Calcium