Journal article
Activated signal transducer and activator of transcription-3 (STAT3) is a poor regulator of tumour necrosis factor-α production by human monocytes
Clinical and Experimental Immunology, Vol.147(3), pp.564-572
2007
Abstract
Signal transducer and activator of transcription-3 (STAT3) activation has been associated with suppressed inflammatory processes in experimental animals, murine myeloid cells and macrophage cell lines. Manipulation of STAT3 activity may therefore be a focus for pharmacological intervention of inflammatory diseases in humans. However, the ability of STAT3 to reduce the production of inflammatory mediators by activated human monocytes and macrophages has been characterized inadequately. To establish this, we used a recently optimized adenoviral approach to study the effect of overexpressed STAT3 or a transcriptionally inactive mutant STAT3 in lipopolysaccharide (LPS)-stimulated human monocytes. STAT3 activated by LPS did not directly regulate inhibitor of kappa B α (IκBα) activation or tumour necrosis factor (TNF)-α production, a process dependent on the transcriptional activity of nuclear factor kappa B (NFκB), although the transcriptional activity of STAT3 contributed to the mechanism by which interleukin (IL)-10 suppressed LPS-induced TNF-α levels. This contrasted with the efficient block in IL-10 induction of suppressor of cytokine signalling-3 (SOCS3) in monocytes infected with an adenovirus expressing mutant STAT3. These results indicate that STAT3 activation cannot directly regulate LPS-signalling in human monocytes and represents only part of the mechanism by which IL-10 suppresses TNF-α production by activated human monocytes. This study concludes that pharmacological manipulation of STAT3 transcriptional activity alone would be insufficient to control NFκB-associated inflammation in humans.
Details
- Title
- Activated signal transducer and activator of transcription-3 (STAT3) is a poor regulator of tumour necrosis factor-α production by human monocytes
- Authors/Creators
- C.M. Prêle (Author/Creator)A.L. Keith-Magee (Author/Creator)M. Murcha (Author/Creator)P.H. Hart (Author/Creator)
- Publication Details
- Clinical and Experimental Immunology, Vol.147(3), pp.564-572
- Publisher
- Oxford Academic
- Identifiers
- 991005540174307891
- Copyright
- © 2007 British Society for Immunology
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.6 Immunology
- 1.6.1264 STAT3 Signaling
- Web Of Science research areas
- Immunology
- ESI research areas
- Immunology