Olha Ilnytska PhD, Simarna Kaur PhD, Suhyoun Chon PhD, Kurt A. Reynertson PhD, Judith Nebus MBA, Michelle Garay MS, Khalid Mahmood PhD, and Michael D. Southall PhD
Johnson & Johnson Skin Research Center, Johnson & Johnson Consumer Inc. Skillman, NJ
Colloidal Oatmeal Helped in the Recovery of Cytokine-induced Barrier Disruption
T-helper cell 2 (Th2)-derived cytokines Il-4, Il-13, IL-31 and pro-inflammatory TNF-α have previously been reported to down-regulate expression of key barrier genes such as fillaggrin (FLG), loricrin (LOR) and involucrin (IVL)10,11 that leads to differentiation defects and reduced lipid envelope reminiscent of atopic dermatitis. To generate inflammatory skin phenotype and therefore weaken skin barrier we exposed developing human epidermis to a cocktail of four above mentioned cytokines. We employed a transepithelial electrical resistance TEER method to quantify the barrier integrity and evaluate TJ barrier function.12 We found remarkable (52%) decrease in TEER at 48 hours after treatment with cytokines compared with the untreated tissues (Figure 3). This condition was significantly alleviated by topical colloidal oatmeal skin protectant lotion treatment (32% of protection compared with cytokines alone).
Colloidal Oatmeal Lotion Significantly Improved Skin Dryness, Hydration and Skin Barrier Integrity In Vivo
Clinical evaluations of skin dryness of individuals with moderate to severe dry skin showed significant improvements (P<0.05) at all time-points during the treatment and regression period with the colloidal oatmeal protectant lotion, including 13 days after the last application when compared to baseline values (Figure 4). Skin was significantly (P<0.05) more hydrated at all time periods measured during both the treatment and regression period. After 3 weeks of treatment, there was highly significant (P<0.05) increase in skin moisture when compared to the baseline mean score. At the end of the regression phase (2 weeks no treatment) mean moisturization values were still significantly higher than baseline suggesting the maintenance of barrier homeostasis. Skin barrier integrity and hydration was also assessed by transepidermal water loss (TEWL) measurements.13 Reduced TEWL values indicated a significant improvement in skin barrier (P<0.05) at all time points during the treatment period and up to day 9 of the regression (no treatment) phase of the study.
The aim of this study was to investigate the mechanism of action of colloidal oatmeal on skin barrier in vitro and in vivo. Treatment of primary human keratinocytes with colloidal oatmeal extracts significantly induced the gene expression of key skin barrier biomarkers that was accompanied by production of involucrin, a protein required for the formation of the cornified envelope (Figure 1). Our study further demonstrates that the topical application of the colloidal oatmeal lotion was able to enhance expression of genes involved in keratinocyte differentiation (TGM1), lipid production (PPARβ/δ, HMGCR and UGCG) and TJ formation (CLDN4 and CLDN7) in the human skin equivalent model (Figure 2) suggesting an enhancement in cornified cell envelope maturation, permeability barrier structure and TJ integrity, respectively, in normal skin.14 The fractions of colloidal oat that resulted in the greatest induction of skin barrier gene expression were the methanol and acetone extracts, which contain phenolic compounds such as flavonoids and avenanthramides, and alcohol-soluble albumin proteins.
The current study determined that colloidal oatmeal protected the epidermal skin barrier from the damage caused by exogenous treatment with cytokines in epidermal skin model of atopic dermatitis. Th2 cytokine treatment in combination with TNF-α perturbs skin barrier by inhibiting differentiation of keratinocytes, inducing cytoskeletal rearrangement and disturbing TJ integrity, and mimics atopic dermatitis skin.10,11,15 Using a skin barrier integrity test we observed a remarkable reduction of TEER following treatment with Th2 cytokines and TNF-α, and the colloidal oatmeal protectant lotion treatment significantly alleviated the damaging effect of cytokines on skin barrier (Figure 3). The inflammation reduction and barrier improvement by colloidal oatmeal can be also potentially triggered by up-regulation of the nuclear hormone receptor PPARβ/δ and its target gene, ANGPTL4. Indeed, PPARα and PPAR β/δ activators significantly inhibited Th2-mediated inflammation and decreased generation of Il1-α and TNF-α in murine model of dermatitis.16 Evidence for the important role of PPARα, PPARβ/δ and LXR activators in regulation of normal and compromised barrier function is emerging.8,16-19 Collectively these in vitro results suggest that the colloidal oatmeal protectant lotion could be beneficial for dry or compromised skin conditions such as xerosis or atopic dermatitis.
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