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Modulation of tumoricidal activity, induced in bone‐marrow‐derived mononuclear phagocytes by interferon γ or Corynebacterium parvum , by interferon β, tumor necrosis factor, prostaglandin E 2 , and transforming growth factor β
Author(s) -
Keller Robert,
Keist Ruth,
van der Meide Peter H.
Publication year - 1991
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910490526
Subject(s) - macrophage , tumor necrosis factor alpha , interferon , biology , cytokine , autocrine signalling , prostaglandin e2 , transforming growth factor , corynebacterium parvum , prostaglandin e , immunology , peripheral blood mononuclear cell , cancer research , microbiology and biotechnology , endocrinology , biochemistry , receptor , in vitro
Among a series of agents, including various interleukins and growth factors, only interferon γ (IFNγ) and heat‐killed Corynebacterium parvum (CP) organisms were able to elicit, within 24 hr, tumoricidal activity in bone‐marrow‐derived mononuclear (BMM) phagocytes. In subsequent experiments, the abilities of interferon β (IFNβ), tumor necrosis factor α (TNFα), prostaglandin E 2 (PGE 2 ), and transforming growth factor β (TFGβ), alone or in combinations of 2, to modulate tumoricidal activity triggered in BMM phagocytes by IFNγ or CP, were compared. In concentrations secreted by macrophages under physiological conditions, these agents proved potent in modulating induction and/or expression of tumoricidal activity. However, their ability to interfere with tumoricidal activity varied considerably, depending on the extent of macrophage differentiation and/or functional responsiveness, the pathway of macrophage activation, the type, concentration and combination of the macrophage secretory molecules, and on whether the agents were present during induction and expression or only during expression of tumoricidal activity. In showing that IFNβ and TNFα were mostly enhancing and TGFβ mostly suppressive, whereas PGE 2 suppressed induction but enhanced expression of tumoricidal activity, our findings provide further support for the concept that these macrophage‐derived molecules have a key role in autocrine regulation of macrophage functional activities.