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its degradation by neutral endopeptidase. SP stimulates degranulation of mast cells and the release of proteases, activating PAR-2 and exacerbating the neurogenic inflammation.
SP and CGRP also interact with many non-
neuronal cells, including endothelial cells, mast cells, immune cells, and arterioles. These in turn contribute additional elements to the inflammatory soup, such as the cytokines IL-6 and IL-8. PAR-2 plays an important role in chronic inflammatory and pruritic skin disorders. For instance, people affected by atopic dermatitis do not experience relief of pruritus through an anti-histaminic therapy. It has been observed that PAR-2, tryptase, and trypsin are up-regulated on lesional skin during atopic dermatitis, and that administration of PAR-2 agonists induces strong pruritus in AD patients, so inhibition of PAR-2 activity could be a novel approach for relieving an itch that does not respond to antihistaminic therapy. Topical treatment with solvents, or following mechanical injury can remove extracellular lipids of the skin disrupting the permeability of the skin barrier. Then, a homeostatic repair response initiates. First, the outermost Stratum Granulosum (SG) cells secret Lamellar Bodies (LB) into the SG/SC interface, and then rapidly form new LB, which propels further, accelerated LB secretion. LB restore lamellar membranes within the SC interstices, thereby normalising permeability barrier function. Proteases and PAR-2 play an important role in the maintenance of epidermal permeability barrier homeostasis. Serine proteases degrade the key lipid processing enzymes required for normal permeability barrier homeostasis. PAR-2 activation is an important signal for regulating LB secretion during the repair response after barrier disruption. Both inhibition and
absence of PAR-2 showed to increase LB secretion and to accelerate barrier recovery following acute disruption. In contrast, PAR-2 activation delay barrier recovery and inhibit LB secretion. Also, acute barrier disruption raises the ambient pH of normal SC transiently from its usual acidic levels (~5.0) toward neutrality, which, in turn, activates serine proteases in the outer epidermis. On the other hand, proteolytic activity from allergens induces allergic inflammation and directly affects the structure and function of epidermal barrier. They could break down the skin barrier via PAR-2 facilitating further penetration of allergens through the defective skin barrier, propagating the vicious cycle of protease-mediated permeability barrier defect. DELISENS™
is a new hexapeptide for cosmetic
products especially designed for sensitive skin, which was identified by a combinatorial chemistry approach using a High Throughput Screening (HTS) from a library of 49,521,980 hexapeptides. The hexapeptide down-regulates PAR-2 activity and as a result CGRP, IL-6 and IL-8 release from skin cells, slowing the inflammatory cycle and reducing the amount of products involved in the inflammatory soup. DELISENS™
helps to recover the barrier skin
function by protecting the human dermal fibroblasts from UV radiation, stimulating human keratinocyte proliferation and restoring the damaged tissue integrity assisting the re-epithelisation and repair of damaged skin. It decreases the nagging pain sensations, discomfort feelings, redness and warming up sensation induced by lactic acid, as it showed in vivo. DELISENS™
promptly improved the stinging
sensation an average of 10.4% after one hour, providing an immediate soothing effect of the skin, and of 25.0% after 7 days of applying a cream
with DELISENS™ .
“
Acute or chronic skin inflammation lowers the threshold for pruritic stimuli which causes a peripheral itch sensitisation
“
In addition, after 7 days of treatment DELISENS™ mitigated the stinging and burning feeling of capsaicin in contact with the skin, improving it by 38.5% compared to a placebo cream at 15 minutes of being exposed to capsaicin. For people suffering from very dry skin, DELISENS™
improved scaling, smoothness and
suppleness, in vivo. It also significantly increased skin moisturising of the legs an average of 34.0% and 39.2% more than a placebo cream, after 1 and 4 weeks of treatment. DELISENS™
is an excellent candidate to diminish
PAR-2 induced release of pro-inflammatory mediators, attenuating skin disorders of sensitive skin and itch related to neurogenic inflammation, as well as helping to restore the barrier function.
Lipotec, Stand K20
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