Proinflammatory transcription factor

Gene regulation by tocopherols has mainly been associated with PKC because of its deactivation by a-tocopherol and its contribution in the regulation of a number of transcription factors (NF-kappaB, API). A direct participation of the pregnane X receptor (PXR)/ retinoid X receptor (RXR) has been also shown. The antioxidant-responsive element (ARE) and the TGF-beta-responsive element appear in some cases to be implicated as well. The obser ved immunmodulatory function of a-tocopherol may also be attributed to the fact that the release of the proinflammatory cytokine interlukin-l 3 can be inhibited by a-tocopherol via... 

A common observation has been that different times are needed for the activation of NFJCB by different stimuli in the case of proinflammatory cytokines the kinetics of the activation is fast, while in the case of H2O2 the kinetics of the activation are slow and sustained. This led to the realization that perhaps different target regions on the IKB were affected by the stimulant, or that other transcription factors were involved. NFJCB is frequently associated with other transcription factors so that they... 

Zhou, H. R., Islam Z., and Pestka J.J. Rapid, sequential activation of mitogen-activated protein kinases and transcription factors precedes proinflammatory cytokine mRNA expression in spleens of mice exposed to the trichothecene vomitoxin. Toxicol. Sci. 72,130,2003. 

Immediately after a report confirmed that the promoter for SEPSl was stimulated by proinflammatory cytokines, and also showed that this promoter was the target of the critical inflammatory regulator NF-kB. The data included direct binding of this transcription factor to the promoter region using gel mobility shift assays. However, the stimulation of the promoter by cytokines and activation of NF-kB did not result in synergistic production of the mRNA. The role that the cytokines or inflammation plays in regulation of expression of selenoprotein S is not yet clear. 

The coupling of superantigen—major histocompatibility complex class II to T-cell receptor swifdy results in cell-signaling cascades. ° These staphylococcal toxins can increase levels of phosphatidyl inositol from quiescent T cells, such as other mitogens, as well as elicit intracellular Ca movement that activates the protein kinase C (PKC) pathway important for interleukin-2 (IL-2) expression. " IL-2 is intimately linked to T-cell proliferation. In addition to the PKC pathway, the protein tyrosine kinase (PTK) pathway is also activated by superantigens, leading to elevated expression of various proinflammatory cytokines. Staphylococcal superantigens also potently activate transcriptional factors NF-/IB (nuclear factor kappa B) and AP-1 (activator protein-1), which subsequently elicit the synthesis of proinflammatory cytokines. " " ... 

Salicylates additionally inhibit the transcription factor NFkb, hence the expression of proinflammatory proteins. This effect is shared with glucocorticoids (p. 248) and ibuprofen, but not with some other NSAIDs. 

STAT4 is very important in mediating proinflammatory immune response, and on the basis of its restrictive distribution of mRNA expression in myeloid and lymphoid tissues, it is evident that STAT4 is a distinct transcription factor. Cytoplasmic STAT4... 

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