ENDOGENOUS INTERFERON-α PRODUCTION BY DIFFERENTIATING HUMAN MONOCYTES REGULATES EXPRESSION AND FUNCTION OF THE IL-2/IL-4 RECEPTOR γ CHAIN

• Published in: Cytokine (Philadelphia, Pa.) Vol. 17; no. 4; pp. 187 - 196
• Main Authors: Bonder, Claudine S., Davies, Kate V.L., Liu, Xiang, Hertzog, Paul J., Woodcock, Joanna M., Finlay-Jones, John J., Hart, Prue H.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 21-02-2002
• Subjects: Cell Differentiation; Coculture Techniques; Humans; IFNα/human/IL-2Rγ/IL-4/monocytes; Interferon-alpha - genetics; Interferon-alpha - immunology; Interferon-alpha - metabolism; Interleukin-1 - metabolism; Interleukin-10 - metabolism; Interleukin-4 - metabolism; Monocytes - cytology; Monocytes - metabolism; Receptors, Interleukin-2 - biosynthesis; Receptors, Interleukin-2 - physiology; Receptors, Interleukin-4 - biosynthesis; Receptors, Interleukin-4 - physiology; RNA, Messenger; STAT6 Transcription Factor; Synovial Fluid - metabolism; Trans-Activators - metabolism; IFNα/human/IL-2Rγ/IL-4/monocytes
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1006/cyto.2001.0994

In vitro monocyte-derived macrophages (MDMac) and synovial fluid macrophages from inflamed joints differ from monocytes in their responses to interleukin 4 (IL-4). While IL-4 can suppress LPS-induced interleukin β (IL-β) and tumour necrosis factor α (TNF-α) production by monocytes, IL-4 can suppress LPS-induced IL-1β, but not TNFα production by the more differentiated cells. Recently we reported a correlation between the ability of IL-4 to regulate TNFα production by monocytes and the expression of the IL-4 receptor gamma chain or gamma common (γc chain). Like MDMac, interferon α (IFNα)-treated monocytes expressed less IL-4 receptor γc chain, reduced levels of IL-4-activated STAT6 and IL-4 could not suppress LPS-induced TNFα production. In addition, like monocytes and MDMac, IFNα-treated monocytes expressed normal levels of the IL-4 receptor α chain and IL-4 significantly suppressed LPS-induced IL-1β production. With addition of IFNα-neutralizing antibodies, the ability of IL-4 to suppress LPS-induced TNFα production with prolonged monocyte culture was restored. Detection of IFNα in synovial fluids from inflamed joints further implicates IFNα in the inability of IL-4 to suppress TNFα production by synovial fluid macrophages. This study identifies a mechanism for the differential expression of γc and varied responses to IL-4 by human monocytes compared with MDMac.