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Cyclosporin A rapidly inhibits mediator release from human basophils presumably by interacting with cyclophilin.
J Immunol. 1990 May 15; 144(10):3891-7.JI

Abstract

We have examined the effects of cyclosporin A (CsA) and a series of CsA analogs that bind with decreasing affinity to cyclophilin, to evaluate the involvement of this protein in the release of preformed (histamine) and de novo synthesized (peptide leukotriene C4; LTC4) mediators of inflammatory reactions from human basophils. CsA (8 to 800 nM) concentration-dependently inhibited (5 to 60%) histamine release from peripheral blood basophils challenged with anti-IgE. CsA was more potent (92.6 +/- 1.8 vs 59.1 +/- 4.5%; p less than 0.001) and, at low concentrations, more effective when the channel-operated influx of Ca2+ was bypassed by the ionophore A23187 (IC40 = 24.1 +/- 3.9 vs 105.5 +/- 22.2 nM; p less than 0.05). CsA had no effect on the release of histamine caused by phorbol myristate and bryostatin 1 that activate different isoforms of protein kinase C. Inhibition of histamine release from basophils challenged with anti-IgE was not abolished by washing (three times) the cells before anti-IgE challenge. CsA also inhibited the de novo synthesis of LTC4 from basophils challenged with anti-IgE. The inhibitory effect of CsA was very rapid, and the drug, added from 1 to 10 min during the reaction, inhibited the ongoing release of histamine caused by anti-IgE and by A23187. The experiments with CsA analogs (CsG, CsC, CsD, and CsH) showed that CsH, which has an extremely low affinity for cyclophilin, has no effect on basophil mediator release. In addition, there is a significant correlation between the concentrations of CsA, G, C, and D that inhibited by 30% the histamine release induced by anti-IgE (r = 0.99; p less than 0.001) and by A23187 (r = 0.87; p less than 0.001) and their affinity for cyclophilin.

Authors+Show Affiliations

Cirillo R
Department of Medicine, University of Naples Federico II, Second School of Medicine, Italy.
Triggiani M
No affiliation info available
Siri L
No affiliation info available
Ciccarelli A
No affiliation info available
Pettit GR
No affiliation info available
Condorelli M
No affiliation info available
Marone G
No affiliation info available

MeSH

Antibodies, Anti-IdiotypicBasophilsBryostatinsCalcimycinCalciumCarrier ProteinsCyclosporinsHistamine ReleaseHumansImmunoglobulin EIn Vitro TechniquesLactonesMacrolidesPeptidylprolyl IsomeraseSRS-ATetradecanoylphorbol Acetate

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

1692065

Citation

Cirillo, R, et al. "Cyclosporin a Rapidly Inhibits Mediator Release From Human Basophils Presumably By Interacting With Cyclophilin." Journal of Immunology (Baltimore, Md. : 1950), vol. 144, no. 10, 1990, pp. 3891-7.
Cirillo R, Triggiani M, Siri L, et al. Cyclosporin A rapidly inhibits mediator release from human basophils presumably by interacting with cyclophilin. J Immunol. 1990;144(10):3891-7.
Cirillo, R., Triggiani, M., Siri, L., Ciccarelli, A., Pettit, G. R., Condorelli, M., & Marone, G. (1990). Cyclosporin A rapidly inhibits mediator release from human basophils presumably by interacting with cyclophilin. Journal of Immunology (Baltimore, Md. : 1950), 144(10), 3891-7.
Cirillo R, et al. Cyclosporin a Rapidly Inhibits Mediator Release From Human Basophils Presumably By Interacting With Cyclophilin. J Immunol. 1990 May 15;144(10):3891-7. PubMed PMID: 1692065.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cyclosporin A rapidly inhibits mediator release from human basophils presumably by interacting with cyclophilin. AU - Cirillo,R, AU - Triggiani,M, AU - Siri,L, AU - Ciccarelli,A, AU - Pettit,G R, AU - Condorelli,M, AU - Marone,G, PY - 1990/5/15/pubmed PY - 1990/5/15/medline PY - 1990/5/15/entrez SP - 3891 EP - 7 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 144 IS - 10 N2 - We have examined the effects of cyclosporin A (CsA) and a series of CsA analogs that bind with decreasing affinity to cyclophilin, to evaluate the involvement of this protein in the release of preformed (histamine) and de novo synthesized (peptide leukotriene C4; LTC4) mediators of inflammatory reactions from human basophils. CsA (8 to 800 nM) concentration-dependently inhibited (5 to 60%) histamine release from peripheral blood basophils challenged with anti-IgE. CsA was more potent (92.6 +/- 1.8 vs 59.1 +/- 4.5%; p less than 0.001) and, at low concentrations, more effective when the channel-operated influx of Ca2+ was bypassed by the ionophore A23187 (IC40 = 24.1 +/- 3.9 vs 105.5 +/- 22.2 nM; p less than 0.05). CsA had no effect on the release of histamine caused by phorbol myristate and bryostatin 1 that activate different isoforms of protein kinase C. Inhibition of histamine release from basophils challenged with anti-IgE was not abolished by washing (three times) the cells before anti-IgE challenge. CsA also inhibited the de novo synthesis of LTC4 from basophils challenged with anti-IgE. The inhibitory effect of CsA was very rapid, and the drug, added from 1 to 10 min during the reaction, inhibited the ongoing release of histamine caused by anti-IgE and by A23187. The experiments with CsA analogs (CsG, CsC, CsD, and CsH) showed that CsH, which has an extremely low affinity for cyclophilin, has no effect on basophil mediator release. In addition, there is a significant correlation between the concentrations of CsA, G, C, and D that inhibited by 30% the histamine release induced by anti-IgE (r = 0.99; p less than 0.001) and by A23187 (r = 0.87; p less than 0.001) and their affinity for cyclophilin. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/1692065/Cyclosporin_A_rapidly_inhibits_mediator_release_from_human_basophils_presumably_by_interacting_with_cyclophilin_ DB - PRIME DP - Unbound Medicine ER -