title: Retinoic acid-stimulated intercellular adhesion molecule-1 expression on SK-N-SH cells: calcium/calmodulin-dependent pathway.
abstract: Intercellular adhesion molecule-1 (ICAM-1) is an important cell surface adhesion receptor of the immune system. Its cell surface expression on a wide variety of cells, including cancer cells, is regulated by various proinflammatory cytokines. In the present study, we investigated the role of calcium (Ca2+) and calmodulin (CaM) in the retinoic acid and gamma-interferon (IFN-gamma) signaling in the human neuroblastoma cell line SK-N-SH for up-regulating ICAM-1 expression. A 24-h incubation in the presence of Ca(2+)-mobilizing agents (A23187 and thapsigargin) resulted in the induction of ICAM-1 expression. Both Ca(2+)-mobilizing agents stimulated ICAM-1 expression additively to IFN-gamma but not to retinoic acid, suggesting that IFN-gamma does not use Ca2+ to stimulate ICAM-1, whereas retinoic acid might use it in part. As a second messenger, Ca2+ can be coupled with calmodulin. Using calmodulin inhibitors (W7 and calmidazolium), we found that retinoic acid-stimulated, A23187-stimulated, and thapsigargin-stimulated but not FIN-gamma-stimulated ICAM-1 were inhibited. Calmodulin signaling elicited by retinoic acid was an early event occurring within the first h of retinoic acid treatment, providing evidence that they may both be coupled to regulate gene expression. Using a novel CaM kinase II inhibitor, KN-62, we demonstrated that retinoic acid stimulated ICAM-1 expression in a CaM kinase II-dependent fashion. The mechanisms whereby CaM kinase II mediates retinoic acid activity on ICAM-1 expression remain to be elucidated.
authors.affiliation: Molecular Endocrinology Laboratory, CHUL Research Center, Quebec, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Bouillon
authors.forename: M
authors.initials: M
authors.lastname: Audette
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis*; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000032:analysis; D013449:Sulfonamides / Q000494:pharmacology; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D002147:Calmodulin; D015815:Cell Adhesion Molecules; D007093:Imidazoles; D007546:Isoquinolines; D010879:Piperazines; D013449:Sulfonamides; D013729:Terpenes; D018799:Intercellular Adhesion Molecule-1; D000001:Calcimycin; C031938:calmidazolium; D014212:Tretinoin; C063302:KN 62; C017967:W 7; D019284:Thapsigargin; D007371:Interferon-gamma; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium