Retinoic acid-stimulated intercellular adhesion molecule-1 expression on SK-N-SH cells: calcium/calmodulin-dependent pathway

Cancer Res. 1994 Aug 1;54(15):4144-9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine* / analogs & derivatives*
  • Calcimycin / pharmacology
  • Calcium / pharmacology*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases / biosynthesis*
  • Calmodulin / antagonists & inhibitors
  • Calmodulin / pharmacology*
  • Cell Adhesion Molecules / metabolism*
  • Enzyme Activation
  • Humans
  • Imidazoles / pharmacology
  • Intercellular Adhesion Molecule-1
  • Interferon-gamma / pharmacology*
  • Isoquinolines / pharmacology
  • Neuroblastoma / metabolism*
  • Piperazines / pharmacology
  • Protein Kinase C / analysis
  • Sulfonamides / pharmacology
  • Terpenes / pharmacology
  • Thapsigargin
  • Tretinoin / pharmacology*
  • Tumor Cells, Cultured
  • Up-Regulation

Substances

  • Calmodulin
  • Cell Adhesion Molecules
  • Imidazoles
  • Isoquinolines
  • Piperazines
  • Sulfonamides
  • Terpenes
  • Intercellular Adhesion Molecule-1
  • Calcimycin
  • calmidazolium
  • Tretinoin
  • KN 62
  • W 7
  • Thapsigargin
  • Interferon-gamma
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Protein Kinase C
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Calcium