Mechanism of action of glucocorticoid-induced immunoglobulin production: Role of lipoxygenase metabolites of arachidonic acid

James Goodwin, D. Atluru

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Glucocorticoids stimulate polyclonal immunoglobulin (Ig) production in cultures of human peripheral blood lymphocytes. The mechanism of action of glucocorticoids in this system, and indeed in any physiologic system, is unknown. Because glucocorticoids stimulate the production of phospholipase A2-inhibitory glycoproteins, we investigated whether glucocorticoids stimulate polyclonal Ig production by inhibition of arachidonic acid metabolism. Nonspecific lipoxygenase/cyclooxygenase inhibitors stimulate polyclonal Ig production in a manner similar to the effect of glucocorticoids, whereas specific cyclooxygenase inhibitors actually inhibit Ig production. Two specific 5-lipoxygenase inhibitors, with little or no activity against cyclooxygenase or other lipoxygenases, also stimulate Ig production. The dose-response effect of all of these drugs on Ig production was similar to the dose response of inhibition of 5-lipoxygenase. Leukotriene B4 (LTB4) added in low concentrations (10-10 M) on days 1, 2, and 3 of a culture eliminated the stimulatory effect of glucocorticoids or 5-lipoxygenase inhibitors, whereas LTC4, LTD4, prostaglandin E, or 5-hydroxyeicosatetraenoic acid had no effect. These results suggest that the relevant action of glucocorticoids in stimulating Ig production might be in preventing endogenous arachidonic acid metabolism, perhaps the endogenous production of LTB4.

Original languageEnglish (US)
Pages (from-to)3455-3460
Number of pages6
JournalJournal of Immunology
Volume136
Issue number9
StatePublished - 1986
Externally publishedYes

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Arachidonate Lipoxygenases
Glucocorticoids
Immunoglobulins
Lipoxygenase Inhibitors
Leukotriene B4
Cyclooxygenase Inhibitors
Arachidonic Acid
Lipoxygenases
Leukotriene D4
Arachidonate 5-Lipoxygenase
Leukotriene C4
Phospholipases A2
Prostaglandin-Endoperoxide Synthases
Prostaglandins E
Glycoproteins
Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Mechanism of action of glucocorticoid-induced immunoglobulin production : Role of lipoxygenase metabolites of arachidonic acid. / Goodwin, James; Atluru, D.

In: Journal of Immunology, Vol. 136, No. 9, 1986, p. 3455-3460.

Research output: Contribution to journalArticle

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