Proinflammatory cytokines regulation

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... 

Wetzel MA, Steele AD, Eisenstein TK, Adler MW, Henderson EE, Rogers TJ (2000) Mu-opioid induction of monocyte chemoattractant protein-1, RANTES, and IFN-gamma-inducible protein-10 expression in human peripheral blood mononuclear cells. J Immunol 165 6519-6524 Widmer U, Manogue KR, Cerami A, Sherry B (1993) Genomic cloning and promoter analysis of macrophage inflammatory protein (MIP)-2, MIP-1 alpha, and MIP-1 beta, members of the chemokine superfamily of proinflammatory cytokines. J Immunol 150 4996-5012 Ye RD (2001) Regulation of nuclear factor kappaB activation by G-protein-coupled receptors. [Review] [136 refs]. J Leukoc Biol 70 839-848... 

In endotoxinemic mice IL-10 treatment inhibits proinflammatory cytokine release and leads to a reduction in LPS toxicity (G8, H28). IL-10 does not influence the LPS-induced production of IL-6 in vivo (M9). This suggests that IL-10 could differentially regulate TNF and IL-6 production by macrophages in vivo, in contrast to data obtained in vitro (Wl), or that cell types other than macrophages are a major source of IL-6 in vivo and are resistant to IL-10 (S23). 

Histamine contributes to the progression of allergic-inflammatory responses by enhancement of the secretion of proinflammatory cytokines like IL-la, IL-1(3, IL-6 as well as chemokines like RANTES or IL-8, both in several cell types and local tissues [26-29]. Endothelial cells express functional HRl and HR2 and increased adhesion molecule expression such as ICAM-1, VCAM-1 and P-selectin was demonstrated by histamine infusion via HRl [30-32]. Histamine regulates the expression of its own receptors on endothelial cells and influences the overall inflammatory reaction [33]. 

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. 

There are several mechanisms whereby antidepressants can modify intracellular events that occur proximal to the posts)maptic receptor sites. Most attention has been paid to the actions of antidepressants on those pathways that are controlled by receptor-coupled second messengers (such as cyclic AMP, inositol triphosphate, nitric oxide and calcium binding). However, it is also possible that chronic antidepressant treatment may affect those pathways that involve receptor interactions with protein tyrosine kinases, by increasing specific growth factor synthesis or by regulating the activity of proinflammatory cytokines. These pathways are particularly important because they control many aspects of neuronal function that ultimately underlie the ability of the brain to adapt and respond to pharmacological and environmental stimuli. One mechanism whereby antidepressants could increase the s)mthesis of trophic factors is... 

Shimada, T., Waranabe, N., Ohtsuka, Y., Endoh, M., Kojima, K., Hiraishi, H., and Terano, A. (1999). Polaprezinc down-regulates proinflammatory cytokine-induced nuclear factor-kappa B activation and interleukin-8 expression in gastric epithelial cells. J. Pharmacol. Exp. Ther. 291, 345-352. 

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