Hydrocortisone inhibits rat basophilic leukemia cell mediator release induced by neutrophil-derived histamine releasing activity as well as by anti-IgE.
We determined the ability of hydrocortisone to inhibit rat basophilic leukemia cell mediator release induced by anti-IgE and by neutrophil-derived histamine-releasing activity (HRA-N). Serotonin release induced by HRA-N and anti-IgE was inhibited by 78 +/- 5 and 70 +/- 4%, respectively (IC50 7.5 x 10(-7)M) by hydrocortisone (10(-5)M). HRA-N does not cause arachidonic acid metabolism, however, anti-IgE induced the generation of PGD2 and leukotriene (LT)C4, and the generation of both mediators was inhibited by 10(-5)M hydrocortisone (IC50 = 4.8 x 10(-7)M, and 3.6 x 10(-9)M, respectively). Inhibition required at least 5 to 6 h of hydrocortisone exposure and was maximal after 22 h. The observed effects of hydrocortisone could be reproduced by human recombinant lipocortin-I (5 x 10(-7)M). Hydrocortisone, 10(-5)M, was a less potent inhibitor of calcium ionophore A23187-mediated serotonin release and PGD2 and LTC4 generation (inhibition of 20 +/- 2, 17 +/- 10, and 37 +/- 10%, respectively). Inasmuch as A23187-induced stimulation is not dependent on receptor coupling, the enhanced ability of hydrocortisone to inhibit IgE- and HRA-N-mediated events as compared with A23187 suggests that one possible site of action of hydrocortisone may be interruption of receptor-effector signals. In the presence of arachidonic acid, hydrocortisone-treated cells released as much LTB4 and PGD2 as control cells, however, serotonin release and LTC4 generation were inhibited 50 and 55%, respectively. Thus, these data suggest that hydrocortisone has three possible sites of action: 1) inhibition of phospholipase A2 activity, 2) inhibition of glutathione-s-transferase, and 3) inhibition of serotonin release by a third mechanism, possibly by interrupting the coupling of receptor and effector systems.
White
M V
MV
National Institutes of Health, National Institute of Allergy and Infectious Diseases, Allergic Diseases Section, Bethesda, MD 20892.
Igarashi
Y
Y
Lundgren
J D
JD
Shelhamer
J
J
Kaliner
M
M
D000818:Animals; D017302:Annexins; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000494:pharmacology; D016207:Cytokines / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007073:Immunoglobulin E / Q000502:physiology*; D066298:In Vitro Techniques; D015471:Leukemia, Basophilic, Acute / Q000378:metabolism*; D008407:Mast Cells / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology; D015230:Prostaglandin D2 / Q000378:metabolism; D051381:Rats; D013189:SRS-A / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D017302:Annexins; D001095:Arachidonic Acids; D002135:Calcium-Binding Proteins; D016207:Cytokines; D013189:SRS-A; D016718:Arachidonic Acid; D012701:Serotonin; D007073:Immunoglobulin E; D015230:Prostaglandin D2; D006854:Hydrocortisone