The antineoplastic agent bryostatin-1 induces proinflammatory cytokine production in human monocytes

Synergy with interleukin-2 and modulation of interleukin-2Rγ chain expression

Maria Caria Bosco, Sandra Rottschafer, Lynn S. Taylor, John R. Ortaldo, Dan L. Longo, Igor Espinoza-Delgado

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The antineoplastic agent bryostatin-1 (bryo-1) possesses powerful immunomodulatory properties and can function as a biological response modifier in vivo. However, there is currently little information regarding the effects of bryo-1 on cells of the monocytic lineage. In this study, we demonstrate that bryo-1 can potently induce the production of proinflammatory cytokines from human peripheral blood monocytes. Stimulation of monocytes with subnanomolar concentrations of bryo-1 significantly upregulated the constitutive levels of interleukin-8 (IL-8) mRNA and induced the expression of IL-1β, tumor necrosis factor-α (TNF-α), and IL-6 mRNA in a time and dose-dependent manner. Accordingly, secretion of all four proinflammatory cytokines was induced after monocyte exposure to bryo-1. Furthermore, we showed that bryo-1 selectively synergized with IL-2 in triggering monocyte activation, and this effect seemed to be dependent, at least in part, on the ability of bryo-1 to upregulate IL-2Rγ chain expression. Finally, we demonstrated that the responses of monocytes to bryo-1 could be blocked by the protein kinase C (PKC) inhibitors staurosporine and UCN-0l, indicating a role for PKC in monocyte activation by bryo-1. These results show for the first time that bryo-1 is a powerful activator of human monocytes and suggest that stimulation of monokine secretion by bryo-1 may represent st least one of the mechanisms responsible for the in vivo antitumor activity of this drug.

Original languageEnglish
Pages (from-to)3402-3411
Number of pages10
JournalBlood
Volume89
Issue number9
Publication statusPublished - May 1 1997

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Interleukins
Antineoplastic Agents
Interleukin-2
Monocytes
Modulation
Cytokines
Protein Kinase C
bryostatin 1
Chemical activation
Monokines
Messenger RNA
Staurosporine
Protein C Inhibitor
Immunologic Factors
Cell Lineage
Protein Kinase Inhibitors
Interleukin-8
Interleukin-1
Interleukin-6
Blood

ASJC Scopus subject areas

  • Hematology

Cite this

The antineoplastic agent bryostatin-1 induces proinflammatory cytokine production in human monocytes : Synergy with interleukin-2 and modulation of interleukin-2Rγ chain expression. / Bosco, Maria Caria; Rottschafer, Sandra; Taylor, Lynn S.; Ortaldo, John R.; Longo, Dan L.; Espinoza-Delgado, Igor.

In: Blood, Vol. 89, No. 9, 01.05.1997, p. 3402-3411.

Research output: Contribution to journalArticle

Bosco, Maria Caria ; Rottschafer, Sandra ; Taylor, Lynn S. ; Ortaldo, John R. ; Longo, Dan L. ; Espinoza-Delgado, Igor. / The antineoplastic agent bryostatin-1 induces proinflammatory cytokine production in human monocytes : Synergy with interleukin-2 and modulation of interleukin-2Rγ chain expression. In: Blood. 1997 ; Vol. 89, No. 9. pp. 3402-3411.
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