Phloxine O, a Cosmetic Colorant, Suppresses the Expression of Thymic Stromal Lymphopoietin and Acute Dermatitis Symptoms in Mice

Abstract

Cosmetics are primarily applied to the skin; therefore, the association of cosmetic dyes with skin diseases or inflammation is a topic of great interest. Thymic stromal lymphopoietin (TSLP) is an interleukin 7-like cytokine that activates dendritic cells to promote Th2 inflammatory immune responses. TSLP is highly expressed in keratinocytes under inflammatory conditions, which suggests that it may play a critical role in the development of skin diseases, such as atopic dermatitis. Therefore, we investigated whether cosmetic dyes influenced the production of TSLP by keratinocytes. Phloxine O, also known as D&C Red No.27, is one of the most common red synthetic pigments and is widely used in colored cosmetics. Our results showed that Phloxine O downregulated phorbol 12-myristate 13-acetate-induced production of TSLP in a murine keratinocyte cell line (PAM212). Phloxine O also suppressed TSLP expression in KCMH-1 cells, which are mouse keratinocytes that constitutively produce high levels of TSLP. To investigate the in vivo effects of Phloxine O, we induced TSLP expression in mouse ear skin by topically applying MC903, a vitamin D3 analogue that is a well-known inducer of atopic dermatitis-like symptoms. Topical application of Phloxine O prevented MC903-induced TSLP production in mouse ear skin, attenuated the acute dermatitis-like symptoms and decreased serum IgE and histamine levels in mice. Suppression of TSLP expression by Phloxine O correlated with reduced expression of OX40 ligand and Th2 cytokines in mouse ear skin. Our results showed that Phloxine O may be beneficial to prevent dermatitis by suppressing the expression of TSLP and Th2 cytokines in skin.

Skin Barrier Abnormalities and Immune Dysfunction in Atopic Dermatitis

“…Downregulation of TSLP expression by dieckol, a phlorotannin compound, is well corroborated by its efficacy in improving AD-like skin symptoms in a house dust mite-induced AD model with NC/Nga mice (Figure 4) [41]. Similarly, phloxine O, a cosmetic dye, reduced TSLP expression in keratinocytes and mouse skin, correlating with alleviation of AD-like symptoms and a decrease in serum IgE and histamine levels in mice (Figure 4) [42]. These results show the positive relationship between the downregulation of TSLP expression and the treatment of AD symptoms.…”

Current Insight into the Role of IL-35 and Its Potential Involvement in the Pathogenesis and Therapy of Atopic Dermatitis

“…TSLP triggers the onset of the inflammatory cascade in AD and has been described as a master regulator of type 2 immune responses [ 69 ]. This proinflammatory cytokine appears to be a promising therapeutic target, and indeed, results of various studies show the association between the downregulation of TSLP expression and an alleviation of the symptoms of AD [ 70 , 71 ]. Several clinical studies are currently ongoing with TSLP as a therapeutic target [ 72 ].…”