Cyclosporin a inhibits ip,-mediated release of calcium from intracellu lar stores in macrophages

Journal Article

Cycloporin A (CsA) and FKöOfi interteie wiHi Ca2+ -nnsimc T-cell sigtial l raii-duct ion pathways, preventing 'he activation of specific transcription fulors involved in lymphokine gene expression. CsA find FK">Oli act by interaction witii (ornate intracellular receptors, cvclophilin and FKBP12, respectively. The drug-recrpior isonicrasc couiitU'xcs inhibit tho Ca2+ /ralmodulin phosphatase, calcineurin and prevent the translocation of transcription factors (NF-AT, wliicli control the induction of early ininuino-response gcno>. from the CVU to the nucleus. FKBP12 i> associated with RyK and IP:)R Ca2+ channels in absence of FK506 FK506 disrupts these complexes by destablizing the inn chantiol which rrsults in altérai ion of Ca2+ rondnctance. Calcinnerin is anrliorod to lP3R via FKBP12 and regulate-, the pliosphorylation slatus of I he nv eptor. resulting in a dynamic Ca2+-sensitive regulation of IP 3-médiat cd flux. We have studied the effects of CsA on IP3, mediated release of Ca2+ from intracelular Ca 2+ stores, on ligation of the α2M signaling receptor. KCJFR. PDGER and HKR with α2M receptor binding fragnu'iit. EGF. PDGF and bradvkiniH. lespoctivclv in imirine periioneai macrophages. Preincuhaüon of cells with CsA (500 ng/ml) had no effect on the synthesis of IP3 and sustained its generation on receptor ligation with the respective ligands. However, if inhibited UN mediated release of Ca2+ from int racellular Ca2+ stores and enTry of Ca2+ from the medium. CV profoundly inhibited RHF-. F.GF- and PIKGF induced DNA synthesis wliich was further reduced on preincubation of cells wild ani.soinycin. CsA also inhibited RUF induced stimulation of micl-Mr PLD activity in macrophages.

Duke Authors

Cited Authors

  • Misra, UK; Gowal, G; Pizzo, SV

Published Date

  • December 1, 1997

Published In

Volume / Issue

  • 11 / 9

International Standard Serial Number (ISSN)

  • 0892-6638

Citation Source

  • Scopus