Anti-inflammatory effect of cyclosporin A on human skin mast cells.
We have examined the effects of cyclosporin A (CsA) and cyclosporin H (CsH), which bind with different affinity to cyclophilin, to evaluate the role of this protein in the release of preformed (histamine) and de novo synthesized (prostaglandin D2[PGD2]) mediators of inflammatory reactions from human skin mast cells (HSMC). CsA (2.4-800 nM)-inhibited (5-60%) histamine release from HSMC challenged with anti-IgE. CsA exerted little, if any, inhibitory effect on histamine release from HSMC challenged with compound A23187 and substance P, whereas it completely suppressed A23187-induced histamine release from human basophils. Inhibition of histamine release from HSMC challenged with anti-IgE was extremely rapid and was not abolished by washing (three times) the cells before anti-IgE challenge. CsA (2.4-800 nM) markedly inhibited (25-70%) the de novo synthesis of PGD2 from HSMC challenged with anti-IgE. CsH, which has an extremely low affinity for cyclophilin, had no effect on skin mast-cell mediator release. These data suggest that CsA is a potent anti-inflammatory agent acting on HSMC, presumably by interacting with cyclophilin.
Stellato
C
C
Department of Medicine, University of Naples Federico II, Second School of Medicine, Italy.
de Paulis
A
A
Ciccarelli
A
A
Cirillo
R
R
Patella
V
V
Casolaro
V
V
Marone
G
G
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology*; D003524:Cyclosporins / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000502:physiology; D007700:Kinetics; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D015230:Prostaglandin D2 / Q000096:biosynthesis; D012867:Skin / Q000166:cytology*
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003524:Cyclosporins; D007073:Immunoglobulin E; D016572:Cyclosporine; C050025:cyclosporin H; D015230:Prostaglandin D2