Features

Protect Skin, Reduce Discomfort

By Marta Rull, Cristina Davi, Elena Cau00f1adas, Juan Cebriu00e1n, Raquel Delgado, Lipotec S.A.U. | September 27, 2013

More people around the world claim to have sensitive skin. Lipotec researchers explain how to enhance skin’s defense against this growing malady.

A high percentage of the population suffers from sensitive skin and every day more people become aware of this condition. However, many consumers never realize that their skin is sensitive and therefore do not take action to improve it. Sensitive skin is normally accompanied by prickling, burning, tingling, pain, itching, erythema, dilated capillaries, hyperpigmentation and/or flush which can be induced and exacerbated by several factors such as pollution, UV radiation, heat, adverse weather, physical activity, diet, stress and substances like soap, cosmetics or even perfumes. As the visible consequences of sensitive skin primarily affect the facial zone, there is a growing interest in attenuating and reducing the discomfort that they cause.

In addition, the same factors that induce sensitive skin alterations can turn normal skin into sensitive skin after exposure. These challenging agents are able to temporarily or permanently weaken the skin’s natural protection system, which becomes sensitized.

What Happens?
Sensitive skin is a cutaneous disorder that is characterized by hyper-reactivity of the skin to external stimuli that increases transepidermal water loss (TEWL), redness and moisture loss, leading not only to a fragile appearance but also to premature wrinkle formation. There is also a proven relationship between the disruption of the permeability of the skin barrier system and the lipids in the stratum corneum (SC). An acute barrier disruption raises the pH of normal SC, activating serine proteases in the outer epidermis that degrade the key processing enzymes required for the homeostasis of the normal permeability of the barrier.1

These alterations already affect personal wellness but they may worsen and lead to inflammatory disorders such as atopic dermatitis (AD) or acne, which share a common pattern of barrier impairment and increased vascular reactivity. Additionally, the threshold for pruritic stimuli is lower in sensitive skin and inflammatory and/or pruritic chronic disorders, which may result in a peripheral itch sensation.

During inflammation, a specific type of sensory neurons liberates peptides and neurotransmitters that result in the release of other products like cytokines, which reinforce inflammation. Expressed in keratinocytes, afferent neurons and inflammatory cells among others, Proteinase Activated Receptor 2 (PAR-2) mediates neurogenic inflammation and participates in this cytokines release, especially of interleukin-6 (IL-6) and interleukin-8 (IL-8).1,2,3

PAR-2 is also involved in the delay of the barrier function recovery, increase of cellular excitability and response to stimuli, via receptors like the Transient Receptor Potential Vanilloid-1 (TRPV1). TRPV1 is a non-selective plasma-membrane ion-channel that mediates the responses to stimuli and participates in neurogenic inflammation, contributing to the presence of additional inflammatory elements like the IL-6 and IL-8.2

When the skin is exposed to allergens for instance, PAR-2 is stimulated inducing allergic inflammation and directly affecting the structure and function of epidermal barrier, whose disruption facilitates the further penetration of the allergens, creating a vicious cycle.1

Inflammatory disorders are linked to facial redness and telangiectasia (dilated capillaries), concentrated in the central third of the face.4 Despite its uncertain origin, facial redness is connected to strong emotions, sport practice, UV radiation, some foods or drinks, adverse weather and certain elements of the natural immune system response, like kallikreins and cathelicidins.4,5

Cathelicidins are potent antimicrobial compounds that promote the expression of Extracellular Matrix (ECM) components and angiogenesis, and coordinate local vascular function.5,6

In humans, these antibiotics are inactive as a pro-protein named 18kDa Cationic Antimicrobial Protein (CAP18) until the proteolytic processing by the skin serine protease kallikrein-5 turns it biologically active as 37-amino-acid peptide (LL-37).5,6

Once activated, LL-37 generates an angiogenic effect and increase of pro-inflammatory metabolites (IL-6, IL-8...) that finally induce capillary dilation, papules, redness, inflammation and, sometimes, post-inflammatory hyperpigmentation.5,6 In inflamed skin, LL-37 expression, as well as IL-6 and IL-8 levels, and cathelicidins, are abnormally high.5,6 Local inflammation reduces skin firmness and elasticity as the degradation of collagen and elastin increases due to the activation of matrix metalloproteinases.

Thus, the elements and events that induce sensitive skin alterations, such as the release of ILs, must be reduced in order to improve skin comfort.

Raising Skin’s Defense
To impede sensitization, the natural defense mechanisms of skin must be enhanced. Although the SC barrier is essential and highly effective against damaging invasions, pathogens sometimes penetrate into the skin layers.

Human defensins are natural antimicrobial peptides with properties that reinforce the immunity and resistance to pathogen invasions. Human-defensins (hBDs) are a group of small cationic peptides characteristic of epithelial tissues that bind microbial membranes and form holes that result in microbial death. While hBD-2 is highly effective against gram-negative bacteria and yeasts, and has a bacteriostatic effect on gram-positive bacteria for example, hBD-3 is broadly effective against gram-negative and gram-positive bacteria as well as fungi.7,8,9 These peptides are scarce in some skin disorders such as AD, where infections are more common, and more frequent in skin with psoriasis and in areas where exposure to microbes is more elevated, which occurs in lesional acne skin.

As the skin is constantly exposed to physical and chemical agents, it is necessary to consider that daily life can really stress it, reduce its own defense mechanisms and even cause cellular alterations, like the intracellular accumulation of abnormally folded proteins (proteotoxic stress). Although protein synthesis normally decreases after stress exposure, this anomalous protein accumulation triggers the synthesis of a group of proteins called Heat Shock Proteins (HSPs), which protect cells from the induced protein destabilization and further damaging exposure to stress.10

The resistance to future cellular damage is transient and unspecific for the triggering stimulus (including hyperthermia, heavy metals, alcohol, UV radiation, oxidative injury, cytokines, inflammation and ischemia), implying tolerance to other stressing conditions that could be lethal.10-12 Although their induced expression under stressing conditions (like the inducible form of the HSP70 family named Hsp72), HSPs are also expressed constitutively in cells. Therefore, the natural defense of skin, such as human defensins and HSPs, must be taken into account to maintain skin equilibrium and avoid unwanted invasions.

Sensitive Skin Solutions
Lipotec proposes two peptides specifically designed to relieve sensitive skin: Delisens (INCI name: Acetyl hexapeptide-49) and Telangyn (INCI: Acetyl tetrapeptide-33). Acetyl hexapeptide-49 is a hexapeptide that attenuates neurogenic inflammation and itching by decreasing PAR-2 activity (by 80.1%), a crucial receptor for both inflammatory signals, and PAR-2-induced release of pro-inflammatory mediators like IL-6 and IL-8 (by 69.6% and 71.4%, respectively). Furthermore, it has an in vitro photoprotective effect (105.9% cell viability increase), helps restore tissue integrity (raises cell proliferation and cicatrisation) and reduces the release of IL-8 induced by cosmetic allergens (in a reconstructed skin model). In volunteers, it minimizes the stinging sensation induced by capsaicin (by 38.5% after 15 minutes, 5% peptide solution) and lactic acid (by 25.0% after 7 days, 2% peptide solution). Analyzing its effect on the damaged barrier function after 1 and 4 weeks, it significantly improves skin hydration (34.0% and 39.2%), dryness, smoothness, softness and suppleness as well. Second, acetyl tetrapeptide-33 decreases facial redness caused by an exaggerated inflammatory response. It reduces the in vitro levels of IL-6 and IL-8 induced by LL-37 (24.2% and 22.8% respectively), shows anti-collagenase and anti-tyrosinase properties (improving firmness and elasticity, and evenness of the skin tone, respectively), and has a photoprotective effect (63.2% cell viability increase). Applied in vivo (2% peptide solution), it minimizes the intensity of erythema (19.2%), redness (17.7%) and its extent (17.9%) as well as the number (8.3%), and size and intensity of the red areas (14.3%) after 28 days.

Protection Enhanced
To improve skin protection, Bodyfensine (INCI name: Acetyl dipeptide-3 aminohexanoate) and Thermostressine (INCI name: Acetyl tetrapeptide-22) help to keep the natural balance and strengthen the existing pathways, so that the skin does not easily turn into sensitive skin.

Acetyl dipeptide-3 aminohexanoate protects the skin from external agents by stimulating human-β-defensine-2 (by 26%) and -3 (by 10%) that ameliorate skin protection. In vivo (5% peptide solution), it increases hydration (by 38%), reduces sebum presence (by 25%) and improves several other skin features after 28 days, as the images demonstrate.

Finally, acetyl tetrapeptide-22 is an ingredient that modulates proteotoxic stress and prevents cellular damage in stressing conditions by stimulating the synthesis of HSP70 (by 28.0%). Keratinocytes treated with this peptide and exposed to heat, cold, UVB (39.0% cell viability increase) or dehydration stress (results equal to non-desiccated cells) showed higher viability and size than the control cells (thermal shock), implying higher protection.

Conclusions
As more people realize they have sensitive skin and that their normal skin can also turn into sensitive skin because of the daily exposure to certain elements, is essential to pay special attention to skin protection and care to avoid suffering distressing consequences. Although they rely on different modes of action, both Delisens and Telangyn specifically decrease the alterations induced by sensitive skin, like itching, pain, flushing, redness, dilated capillaries and hyperpigmentation. Bodyfensine and Thermostressine reinforce the skin’s natural defensive mechanisms along with the response toward stressing situations that may terminate in cellular damage. Therefore, these peptides ameliorate the comfort of sensitive skin and protect normal skin from the same disturbing alterations. 


References
  1. Lee SE, Jeong SK, Lee SH. Protease and protease-activated receptor-2 signaling in the pathogenesis of atopic dermatitis. Yonsei Med J. 51(6): 808 – 822, 2010.
  2. Paus R, Schmelz M, Bíró T et al. Frontiers in pruritus research: scratching the brain for more effective itch therapy. J Clin Invest. 116(5): 1174 – 1186, 2006.
  3. Dai Y, Moriyama T, Higashi T et al. Proteinase-activated receptor 2-mediated potentiation of transient receptor potential vanilloid subfamily 1 activity reveals a mechanism for proteinase-induced inflammatory pain. J Neurosci. 24(18): 4293 – 4299, 2004.
  4. Culp B, Scheinfeld N. Rosacea: a review. Pharmacy and Therapeutics. 34 (1): 38-45, 2009.
  5. Bevins CL, Liu F-T. Rosacea: skin innate immunity gone awry? Nat Med. 13 (8): 904-906, 2007.
  6. Yamasaki K, Nardo A, et al. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat Med. 13 (8): 975-80, 2007.
  7. Harder J, Schröder JM. Psoriatic scales: a promising source for the isolation of human skin-derived antimicrobial proteins. J Leukoc Biol. 77: 476-486, 2005.
  8. Schneider JJ, Unholzer A, Schaller M, et al. Human defensins. J Mol Med. 83: 587-595, 2005.
  9. Nagy I, Pivarcsi A, Koreck A, et al. Distinct strains of Proionibacterium Acnes induce selective human β-defensin-2 and interleukin-8 expression in human keratinocytes through toll-like receptors. J Invest Dermatol. 124: 931-938, 2005.
  10. Jonak C, Klosner G, Trautinger F. Heat shock proteins in the skin. Int J Cosm Sci. 28: 233 – 241, 2006.
  11. Laplante AF, Moulin V, Auger FA, Landri J, Li H, Morrow G, Tanguay RM, Germain L. Expression of heat shock proteins in mouse skin during wound healing. J Histochem & Cytochem. 46(11): 1291 – 1301, 1998.
  12. Fargnoli J, Kunisada T, Fornace AJ, Schneider EL, Holbrook NJ. Decreased expression of heat shock protein 70 mRNA and protein after heat treatment in cells of aged rats. Proc Natl Acad Sci USA. 87: 846 850, 1990.

More info: Caroline Keller, customer relations and marketing manager, Lipotec LLC, 22 Hudson Place – Suite 4N, Hoboken, NJ 07030 US; Email: salesoffice@lipotec.com; Tel. (201) 850-1213; Fax: (201) 850-1212; Website: www.lipotec.com

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