Inflammation Mediators

Glucocorticoids have been shown to inhibit gene transcription of other proteins involved in the inflammatory process, including the key inflammation mediators called cytokines (IL-1, IL3—6, IL8, GM-CSF, TNFa) (10,58,63—65). Steroids have been also shown to suppress the formation of cytokine receptors (10) dexamethasone, in particular, downregulates gene transcription of angiotensin II type 2 receptors (66). 

The drug SC-558 acts by a fourth mechanism, specifically inhibiting COX-2. It is a weak competitive inhibitor of COX-1 but inhibits COX-2 in a slow, time-dependent process. Specific COX-2 inhibitors will likely be the drugs of the future because they selectively block the inflammation mediated by COX-2, without the potential for stomach lesions and renal toxicity that arise from COX-1 inhibition. 

Block, M. L. Hong, J. S. (2005). Microglia and inflammation-mediated neurodegeneration multiple triggers with a common mechanism. Prog. Neurobiol., 76(2), 77-98. 

Feng-Qiao L, Xiu-Zhi L., Xi-Bin L, et al. Triptolide, a Chinese herbal extract, protects dopaminergic neurons from inflammation-mediated damage through inhibition of microglial activation. J Neuroimmunol 2004 148 24-31. 

Liu, B., Hong, J.S. (2003) Rome of microglia in inflammation-mediated neurodegenerative diseases mechanisms and strategies for therapeutic intervention. J. Pharmacol. Exper. Ther., 304, 1-7. 

Src is the prototype of the superfamily of protein tyrosine kinases and was one of the first protein kinases to be characterized by various genetic, cellular, and structure-function studies to help imderstand its role in signal transduction pathways as well as in disease processes, including cancer, osteoporosis, and both tumor- and inflammation-mediated bone loss [28-38]. In fact, studies on Src provided some of the first evidence correlating protein kinase activity and substrate protein phosphorylation in the regulation of signal transduction pathways relative to normal cellular activity as well as mahgnant transformations. Src family kinases include Fyn, Yes, Yrk, Blk, Fgr, Hck, Lyn,... 

Dinarello CA. 2000. The role of interleukin-1 receptor antagonist in blocking inflammation mediated by IL-1. NEJM. 343 732-734. 

Since histamine is the main mediator of the allergic inflammation during both early and late phases, it is necessary to apply modern selective HI blockers (for example, ebastine, loratidine or cetirizine) in a parallel way to SLIT. This eliminates minimal persistent inflammation. It becomes evident on the cellular level and can be assessed by the presence of cellular inflammation mediators, interleukins and epithelial expression of adhesion molecules, but without clinical symptoms of allergy [14, 15],... 

Muller N. and Schwarz M. (2006). Schizophrenia as an inflammation-mediated dysbalance of gluta-matergic neurotransmission. Neurotox. Res. 10 131-148. 

The expression of genes associated with excitotoxicity, oxidative stress, and inflammation-mediated apoptosis is controlled through cytokines and chemokines... 

Endothelial cells Chronic proinflammatory response Leukocyte infiltration (rolling and adhesion), vascular dilation, inflammation mediator release (e.g., histamine, cytokines, eicosanoids)... 

Several in vitro methods have been developed which use different end points to measure skin irritation (e.g. measurement of inflammation mediator, effects on survival rates of special cell lines, etc.) However, as stated for the Draize test they do not play a significant role. 

Liu B, Horrg IS (2003) Role of microglia in inflammation-mediated neurodegerrerative diseases Mecharrisms and strategies for therapeutic irrterverrtiorr. J Pharmacol Exp Ther 304 1—7. 

Boswellinic acids Leukotrienes appear to play a special role as inflammation mediators in the pathogenesis of PBC they also correlate closely with the increase in cholestasis-indicating enzymes. Boswellinic acids are selective non-redox inhibitors of 5-lipoxygen-ase and therefore inhibit leukotriene biosynthesis. So far, they have not been used in PBC treatment. Based on existing pharmacological data, their application should now be considered. 

Liu B, Gao HM, Wang JY, Jeohn GH, Cooper CL, Hong JS (2002) Role of nitric oxide in inflammation-mediated neurodegeneration. Ann NY Acad Sci 962 318-331. 

Ciclosporin oU-in-water emulsion has been used in the local treatment of moderate to severe dry eye disease. Chronic dry eye disease results from inflammation mediated by cytokines and receptors for autoimmune antibodies in the lacrimal glands. It affects the lacrimal gland acini and ducts, leading to abnormahties in the tear film, and ultimately disrupting the homeostasis of the ocular surface. Topical ciclosporin reduces the cell-mediated inflammatory response associated with inflammatory ocular surface diseases. 

Rat peritoneal mast cells Inflammation mediator release Yes (surfactant)... 

R, Kim SK (2013) Neoechinulin A suppresses amyloid-p oligomer-induced microglia activation and thereby protects PC-12 cells from inflammation-mediated toxicity. 

Bollrath J, Greten FR (2009) IKK/NF-kappaB and STAT3 pathways central signalling hubs in inflammation-mediated tumour promotion and metastasis. EMBO Rep 10(12)4314-1319. doi 10.1038/embor.2009.243... 

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