Differential induction of human monocyte transforming growth factor beta 1 production and its regulation by interleukin 4.
We have previously shown that trauma patients' monocytes which are in vivo activated by multiple injury-induced mediators have elevated transforming growth factor-beta (TGF beta) bioactivity. Interleukin-4 (IL-4), a Th2 and B lymphocyte stimulatory factor, has been shown to inhibit monocyte production of a number of mediators both after lipopolysaccharide stimulation and after trauma-induced stimulation. However, IL-4 inhibitory effects appears to vary, depending on the mixture of inducing stimuli. Here we describe the in vitro IL-4 inhibition of human monocyte TGF beta bioactivity using several stimulation induction protocols: muramyl dipeptide stimulation alone, or after Fc gamma RI (CD64) cross-linking induction, interferon-gamma (IFN gamma) priming, or trauma-generated in vivo mediator induction. IL-4 suppressed both muramyl dipeptide-induced TGF beta bioactivity and TGF beta mRNA in a dose-dependent fashion and was most effective when IL-4 was administered at initiation of normal monocyte stimulation. Muramyl dipeptide (MDP)-induced increases in trauma patients' monocyte TGF beta bioactivity were also inhibited by high doses of IL-4 (25 ng/ml). Fc gamma RI cross-linking increased MDP-induced normal monocyte TGF beta bioactivity, but this increase could be consistently inhibited only by very high IL-4 concentrations (50 ng/ml). IL-4 did not consistently downregulate MDP-induced TGF beta bioactivity in IFN gamma-primed monocytes. IL-4 can suppress monocyte TGF beta production, as well as other monocyte mediators, but its efficiency depends on the stimuli combination present in the microenvironment.
Miller-Graziano
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CL
Department of Surgery, University of Massachusetts Medical Center, Worcester 01655.
Zhu
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Kodys
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D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000276:immunology; D015152:Blotting, Northern; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology*; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D014947:Wounds and Injuries / Q000276:immunology
D012333:RNA, Messenger; D017452:Receptors, IgG; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D007371:Interferon-gamma