Receptor-mediated inflammatory

Chronic dry eye is the result of an underlying cytokine and receptor-mediated inflammatory process that affects the ocular surface and lacrimal gland, leading to decreased tear production or altered tear film contents. Hormonal, anti-inflammatory, or immunomodulatory agents may be able to suppress the inflammation and normalize the neural reflex between the ocular smrfece and lacrimal glands. 

Inhibition of inflammatory cytokines (Fig. 2) Humanized monoclonal anti-TNF antibodies (Infliximab (Remicade ), Adalimumab (Humira )) bind with high selectivity to human TNF-a and neutralize its activity. Thereby, infliximab decreases the effects of enhanced TNF levels during inflammatory disease such as production of proteases, chemokines, adhesion molecules, cyclooxygenase products (prostaglandins), and proinflammatory molecules such as interleukin-1 and -6. The antibodies may also recognize membrane-bound TNF-a on lymphocytes and other immune cells. These cells may subsequently become apoptotic or are eliminated via Fc-receptor-mediated phagocytosis. 

The beta 2 family has receptors on leukocytes (also called LeuCAM) and mediates inflammatory and immune recognition functions. 

Several of the postulated roles for nematode-secreted AChEs assume that they gain access to the intestinal mucosa. Several possibilities exist for transport of parasite AChE across the epithelial cell barrier, such as (i) utilization of existing pathways for receptor-mediated transcytosis (ii) a paracellular route facilitated by parasite-secreted proteases as observed for a bacterial elastase (Azghani et al., 1993) and (iii) increased paracellular permeability resulting from inflammatory events in the mucosa. We consider the latter suggestion most likely, as this has been duplicated by ex vivo perfusion with rat mast cell protease II (Scudamore et al., 1995). Moreover, cholinergic stimulation attenuates epithelial barrier properties to macromolecules in rat ileal crypts (Phillips et al., 1987). 

CC Chemokine Receptor 2 (CCR2) is a member of the G protein-coupled receptor (GPCR) superfamily that serves as the receptor for monocyte chemoattractant proteins 1-4 (MCP-1 to -4), a group of pro-inflammatory chemotactic cytokines (chemokines). CCR2 is the primary chemokine receptor on inflammatory monocytes, and is also expressed on T-cells, dendritic cells, and endothelial cells. Upon ligand engagement, CCR2 mediates both cellular movement and activation. 

TNF-a and IL-1 are current targets of antiinflammatory drug therapy. A homotrimer of 17-kDa protein subunits whose effects include the activation of neutrophils and eosinophils, induction of COX-2, induction of proinflammatory cytokines (e.g., IL-1, IL-6), enhancement of endothelial layer permeabihty, induction of adhesion molecules by endothelial cells and leukocytes, stimulation of fibroblast proliferation, degradation of cartilage, and stimulation of bone reabsorption. Two receptors mediate these effects a 55-kDa receptor (p55) and a 75-kDa receptor (p75). Each of these receptors is found in both cell surface and soluble forms. The binding of two or three cell surface receptors to TNF-a initiates an inflammatory response. Soluble p55 also acts as a signaling receptor for inflammatory responses, whereas soluble p75 acts as an antagonist. 

Bhattacharyya S, Brown DE, Brewer JA, Vogt SK, Muglia LJ. Macrophage glucocorticoid receptors regulate Toll-like receptor-4-mediated inflammatory responses by selective inhibition of p38 MAP kinase. Blood 2007, 109, 4313M319. 

Dimitriadou V, Rouleau A, Trung Tuong MD, Newlands GJ, Miller HR, Luffau G, Schwartz JC, Garbarg M (1997) Functional relationships between sensory nerve fibers and mast cells of dura mater in normal and inflammatory conditions. Neuroscience 77 829-39 Dolezal V, Jackisch R, Hertting G, AUgaier C (1992) Activation of dopamine D] receptors does not affect D2 receptor-mediated inhibition of acetylcholine release in rabbit striatum. Naunyn Schmiedeberg s Arch Pharmacol 345 16-20... 

Many studies showed that peptidoglycan in the cell wall stimulates macrophages, antibody formation, and T lymphocyte activity entering the intestine (Dziarski 1991). Certain strains of LAB induce pro-Thl responses, promoted through the receptor-mediated cytokine pathway, and the ability of individual cell wall compounds to induce pro-IFN cytokines (especially IL-12) at a sub-inflammatory level. However, it should be realized that other indirect LAB-induced modulatory mechanisms may also be operative in combating atopy, such as their ability to liberate de novo immunoregulatory peptides from major food proteins via enzymatic hydrolysis. This mechanism has been demonstrated experimentally for some LAB (Matar et al. 1996, Rokka et al. 1997). 

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