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Publication : IL-4 inhibits the production of TNF-alpha and IL-12 by STAT6-dependent and -independent mechanisms.

First Author  Levings MK Year  1999
Journal  J Immunol Volume  162
Issue  9 Pages  5224-9
PubMed ID  10227996 Mgi Jnum  J:112259
Mgi Id  MGI:3655923 Doi  10.4049/jimmunol.162.9.5224
Citation  Levings MK, et al. (1999) IL-4 inhibits the production of TNF-alpha and IL-12 by STAT6-dependent and -independent mechanisms. J Immunol 162(9):5224-9
abstractText  IL-4 promotes allergic responses and inhibits the production of proinflammatory cytokines by monocytes and macrophages. The promotion of allergic responses by IL-4 has been shown to be absolutely dependent on the transcription factor STAT6. We report here that the inhibitory effects of IL-4 on the production of TNF-alpha or IL-12 by macrophages had both STAT6-dependent and -independent components, depending on the stimuli. IL-4 failed to inhibit the release of TNF-alpha or IL-12 from STAT6 null macrophages stimulated with LPS alone. However, IL-4 still induced significant inhibition of the production of TNF-alpha and IL-12 from STAT6 null macrophages that were stimulated with the more physiologically relevant combination of LPS and IFN-gamma. These data show that STAT6 is required for the IL-4-mediated inhibition of the production of TNF-alpha and IL-12 stimulated by LPS alone, but that IL-4 also activates distinct, STAT6 independent mechanism(s) that inhibit the IFN-gamma-mediated enhancement of IL-12 and TNF-alpha production.
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