title: IL-4 antagonizes induction of Fc gamma RIII (CD16) expression by transforming growth factor-beta on human monocytes.
abstract: The multifunctional cytokines, transforming growth factor (TGF)-beta 1 and beta 2, have the capability of inducing human peripheral blood monocytes to express the type III receptor for the Fc portion of IgG (Fc gamma RIII/CD16). In this study we show that the T cell-derived cytokine, IL-4, antagonizes the ability of TGF-beta to induce the expression of CD16. Furthermore, this ability to down-regulate expression of CD16 is completely abrogated after treatment with polyclonal anti-IL-4, suggesting that IL-4 is solely responsible for the observed inhibition. The mechanism for negating the effect of TGF-beta is not due to decreased expression of surface receptors for TGF-beta, but appears to occur at the mRNA level. Nuclear run-off assays indicate that regulation occurs predominantly through a posttranscriptional mechanism(s), although a transcriptional process cannot be ruled out. Normally, CD16 appears on only a small population of circulating monocytes, however, expression is apparent on the majority of mature tissue and inflammatory macrophages likely due to the release of TGF-beta in these sites. Inasmuch as this receptor binds immune complexes and opsonized particles, it is associated with enhanced immunophagocytosis. Suppression of CD16 expression and its ability to suppress a number of other monocyte functions suggests that IL-4 may play an important role in the resolution of inflammatory and tissue repair responses.
authors.affiliation: Laboratory of Immunology, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.
authors.forename: H L
authors.initials: HL
authors.lastname: Wong
authors.forename: G R
authors.initials: GR
authors.lastname: Welch
authors.forename: M E
authors.initials: ME
authors.lastname: Brandes
authors.forename: S M
authors.initials: SM
authors.lastname: Wahl
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D015152:Blotting, Northern; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000494:pharmacology*; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface / Q000378:metabolism; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism*; D017452:Receptors, IgG; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011961:Receptors, Fc; D017452:Receptors, IgG; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D015847:Interleukin-4