Inflammatory pathways

Corticosteroids are the most potent anti-inflammatory agents available for the treatment of asthma. The efficacy of corticosteroids is due to their ability to affect multiple inflammatory pathways, resulting in the suppression of inflammatory cell activation and function, prevention of microvascular leakage, decreased mucus production, and upregulation of P2-adrenergic receptors.10,18 Clinically, corticosteroids decrease airway inflammation, decrease AHR, decrease mucus production and secretion, and improve the response to P2-agonists.18 Corticosteroids for the treatment of asthma are available in inhaled, oral, and injectable dosage forms. 

Land WG. The role of postischemic reperfusion injury and other nonantigen-dependent inflammatory pathways in transplantation. Transplantation 2005 79 505-514. 

As already mentioned, van Kuijk and colleagues (Kalariya et al., 2008) tested the effects of oxidation products of [i-carotcnc, lutein, and zeaxanthin on the activation of redox-sensitive transcription factors, NF-kB, and AP-1 in cultured ARPE-19 cells. Degradation products of all three carotenoids induced activation of NF-kB and AP-1, and these effects were ameliorated by pretreatment of cells with 1 mM NAC. NF-kB is a major transcription factor that binds to promoter sites of many pro-inflammatory cytokines such as IL-1, IL-6, TNF-a, and iNOS. These results indicate that the degradation products of carotenoids can stimulate a pro-inflammatory pathway. 

JP-8-induced systemic immunosuppression is explained in part by modulation of cytokine and inflammatory pathways. Within 48 hours of a single dermal application of JP-8 (300 pL), serum IL-10 levels increase significantly to nearly 3000 pg/mL [36], As IL-10 is known to suppress DTH responses [64,65], it is likely that modulation of this cytokine contributes to JP-8 s immunotoxicity. Furthermore, splenic T-cell proliferative responses are significantly decreased in JP-8 exposed mice, yet this effect is reversed following neutralization of IL-10, administration of IL-12, or inhibition of prostaglandin E2 (PGE2) production [60], Additional studies demonstrated suppression... 

P2-adrenergic receptors may function similar to HR2 in humans [196,197]. The role of histamine and other redundant G-protein-coupled receptors in the regulation of inunune/inflammatory pathways in allergic inflammation remain to be intensely focused in future studies. 

Ryan S, Taylor CT, McNicholas WT. Selective activation of inflammatory pathways by intermittent hypoxia in obstructive sleep apnea syndrome. Circulation. Oct 25 2005 112(17) 2660-2667. 

Classically, inflammation is a protective reaction of the body in response to some physical, chemical, or microbial injury and insult of the cells. Acute inflammation, rapid onset and shorter duration, is considered as a healthy response. However, when inflammation continues for prolonged period of time, it becomes detrimental and may raise the first step of a chronic disease (Medzhitov, 2008). Arachidonic acid/COX and nuclear factor- (NF- ) are well known inflammatory pathways which induce production of inflammatory mediators such as prostaglandins, thromboxanes, leukotrienes, and cytokines. Most commonly accepted mechanism of anti-inflammation is inhibition of cyclooxygenase (COX) activity. There are two kinds of cyclooxygenases COX-1 is natural protective enzyme of intestinal mucosa while COX-2 is induced by tissue damage as an inflammatory mediator (Maroon et al., 2006). NF- is a recently identified... 

Bellenger, J., Bellenger, S., Bataillem, A., Massey, K. A., Nicolaou, A., Rialland, M., Tessier, C., Kang, J. X., and Narce, M. (2011). High pancreatic n-3 fatty acids prevent STZ-induced diabetes in fat-1 mice Inflammatory pathway inhibition. Diabetes 60,1090-1099. 

Lukashev D, Ohta A, Sitkovsky M (2007) Hypoxia-dependent anti-inflammatory pathways in protection of cancerous tissues. Cancer Metastasis Rev 26(2) 273-279 MacKenzie WM, Hoskin DW, Blay J (1994) Adenosine inhibits the adhesion of anti-CD3-activated killer lymphocytes to adenocarcinoma cells through an A3 receptor. Cancer Res 54(13)3521-3526... 

To fully understand the actual mechanism of action of dietary flavonoids either as antioxidants, modulators of cell signalling, or inflammatory pathways, it is important to detect and identify their metabolites in vivo as well as to study the consequences of interaction of these circulating metabolites with cells. Animal models and human studies should also be conducted to identify the in vivo mechanism of action of dietary flavonoids. Results of such studies are crucial in the evaluation of their potential as cardiovascular protective agents and may eventually lead to specific advice regarding intake of foods and beverages rich in flavonoids and attempts to alter and enhance flavonoid content of a range of foods. 

These results taken together show that abciximab is an effective agent in preventing acute coronary syndromes based on its inhibition of platelet GP Ilb/IIIa and probably also of 0 3 and Mac-1, which thereby induces interference with several thrombogenic and inflammatory pathways. 

Knowlton KU, Chien KR. Inflammatory pathways and cardiac repair The affliction of infarction. Nat Med 1999 5 1122-1123. 

Thus it can be seen that anti-ChEs are vahd inducers of the cholinergic anti-inflammatory pathway, presumably through their role in increasing ACh levels. 

Gallowitsch-Puerta, M., Tracey, K.J. (2005). Immunologic role of the cholinergic anti-inflammatory pathway and the nicotinic acetylcholine alpha 7 receptor. Ann. NY Acad. Sci. 1062 209-19. 

Figueiredo-Pereira et al. discovered that proteasome inhibition leads to accumulation of ubiquitinated proteins [56]. Proteasome inhibition is also connected with the activation of the cellular stress response including an increased expression of HSP 70 and activation of the inflammatory pathway shown by the increase of COX-2 expression and the production of the pro-inflammatory prostaglandin PGE2. An interaction of these two pathways may happen in the cascade of events leading to neurodegeneration [56]. 

Pavlov VA, Tracey KJ (2005) The cholinergic anti-inflammatory pathway. Brain Behav Immun 19 493-9. 

Chen Y, Langrish CL, McKenzie B, Joyce-Shaikh B, Stnmhofer JS, McClanahan T, Blumenschein W, Churakovsa T, Low J, Presta L, Hnnter CA, Kastelein RA, Cua DJ (2006) Anti-IL-23 therapy inhibits mnltiple inflammatory pathways and ameliorates antoim-mnne encephalomyelitis. J Clin Invest 116 1317-1326. 

A recent study has provided insight into the association of ambient air pollution with increased cardiovascular morbidity and mortality. In this study, when human microvascular endothelial cells were exposed to a combination of ultrafine diesel exhaust particles and oxidized lipid components, a synergistic effect on the expression profiles of several gene modules that correspond to pathways relevant to inflammatory pathways such as atherosclerosis was observedJ57l The implications of this study include a greatly increased risk of heart disease in those with high cholesterol who breathe polluted air. 

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