Hydrocortisone inhibits rat basophilic leukemia cell mediator release induced by neutrophil-derived histamine releasing activity as well as by anti-IgE.

Article Details

Citation
Copy to clipboard

White MV, Igarashi Y, Lundgren JD, Shelhamer J, Kaliner M

Hydrocortisone inhibits rat basophilic leukemia cell mediator release induced by neutrophil-derived histamine releasing activity as well as by anti-IgE.

J Immunol. 1991 Jul 15;147(2):667-73.

PubMed ID
1712816 [ View in PubMed
]
Abstract

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.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
HydrocortisoneAnnexin A1ProteinHumans
Yes
Agonist
Details
Hydrocortisone aceponateAnnexin A1ProteinHumans
Yes
Not AvailableDetails
Hydrocortisone acetateAnnexin A1ProteinHumans
Yes
Not AvailableDetails
Hydrocortisone butyrateAnnexin A1ProteinHumans
Yes
Not AvailableDetails
Hydrocortisone cypionateAnnexin A1ProteinHumans
Yes
Not AvailableDetails
Hydrocortisone phosphateAnnexin A1ProteinHumans
Yes
Not AvailableDetails
Hydrocortisone probutateAnnexin A1ProteinHumans
Yes
Not AvailableDetails
Hydrocortisone valerateAnnexin A1ProteinHumans
Yes
Not AvailableDetails