Editors’ Picks from Experimental Dermatology (February and March issues)

Chrysanthemum extract apigenin improves barrier repair after tape stripping

Apigenin, a chrysanthemum extract, has been used for skin care in Asia for ages but knowledge on how this agent acts is scarce. It was shown before that apigenin exhibits preventive activity against UVB-induced skin tumors (Tong et al., 2007),and that an apigenin-enriched diet attenuates the development of atopic dermatitis-like lesions (Yano et al 2009).

The Man group (2013) now reports the influence of apigenin on early skin barrier repair after tape stripping in murine skin. Treatment with apigenin resulted in elevated filaggrin expression, increased density of lamellar bodies, and more intense immunostaining for antimicrobial peptides. In cultured human keratinocytes, addition of apigenin resulted in elevated mRNA levels of the lipid-synthesizing enzymes HMGCoA, SPT1, and FAS. In summary, this report demonstrates a positive effect of apigenin on skin barrier repair and highlights that various mechanisms may contribute to this effect. Treatment of diseases with barrier repair dysfunction may therefore be a future field of application for apigenin.

Selected by J. Brandner, Hamburg, Germany

Maihua Hou, Richard Sun, Melanie Hupe, Peggy L. Kim, Kyungho Park, Debra Crumrine, Tzu-kai Lin, Juan Luis Santiago, Theodora M. Mauro, Peter M. Elias and Mao-Qiang Man (2013) Topical Apigenin Improves Epidermal Permeability Barrier Homeostasis in Normal Murine Skin by Divergent Mechanisms. Exp Dermatol Accepted manuscript online: 30 JAN 2013 doi: 10.1111/exd.12102, will be published in Vol 22, Nr. 3, March 2013

Tong X, Van Dross RT, Abu-Yousif A, Morrison AR, Pelling JC (2007) Apigenin prevents UVB-induced cyclooxygenase 2 expression: coupled mRNA stabilization and translational inhibition.  Mol Cell Biol. Jan;27(1):283-96.

Yano S, Umeda D, Yamashita S, Yamada K, Tachibana H (2009) Dietary apigenin attenuates the development of atopic dermatitis-like skin lesions in NC/Nga mice.  J Nutr Biochem. Nov;20(11):876-81



Functional melanocortin 1 receptor Mc1r is not necessary for an inflammatory response to UV radiation in adult mouse skin

Melanocortin receptor type 1 (MC1R) is recognized for its role in the regulation of melanin pigmentation. In addition, a majority of investigators believes that it also plays a crucial role in anti-inflammatory responses and in induction of protective responses counteracting the damaging effects of ultraviolet radiation (UVR).

Most recently, researchers from George Washington University and Jagiellonian University (2013), using C57BL/6-c, C57BL/6, and C57BL/6-Mc1re/e  mouse strains, have reported the surprising finding that loss of function in the MC1R neither impacts  inflammatory responses to UV nor affects  UVR-induced immunosuppression. These findings are in striking contrast with the generally accepted opinion that constitutive or ligand-induced MC1R activity plays an important role in modulation of cutaneous immune activity in response to UVR. Interestingly, the authors also showed that UVR induced similar DNA damage in the epidermis and dermis of C57BL/6-c, C57BL/6, and C57BL/6-Mc1re/e strains of mice.

By challenging the existing dogmas on the precise role of MC1R in non-pigmentary responses to the UVR, these results will undoubtly stimulate further research to validate the presented data or to determine to which degree these phenomena extend beyond the C57BL/6 mouse model.

Selected by A. Slominski, Memphis, USA

Wolnicka-Glubisz A, De Fabo E,  Noonan F. (2013) Functional melanocortin 1 receptor Mc1r is not necessary for an inflammatory response to UV radiation in adult mouse skin. Exp Dermatol Accepted manuscript online: 25 JAN 2013 doi: 10.1111/exd.12100.





Human follicular dermal cells support keratinocyte growth: trichogenicity is a virtue?

Autologous transplantation of artificially assembled epidermal sheet has been used for the treatment of severe burns, intractable ulcers, and genodermatoses. Rapid in vitro expansion of patient-derived keratinocytes is a key step for successful treatment. Among currently available keratinocyte culture techniques, the one established by Rheinwald and Green (R&G) in 1975 is still considered to be very efficient. Yet, this protocol requires inactivated 3T3 murine feeder cells and “specially mixed” culture medium (I hope that everyone agrees that it is a bit of a hassle to prepare).

Hill et al. (2013) demonstrated that human dermal papilla (DP) and dermal sheath (DS) cells support human keratinocyte growth in orthodox MEM medium at a level comparable to that achieved with R&G’s condition.  The authors also showed that secreted protein acidic and rich in cysteine (SPARC) expression levels correlated with improved keratinocyte support. Yet, forced expression of SPARC in human dermal fibroblasts was not sufficient to endow these cells with such supportive properties.

DP and DS cells possess hair- inductive capacities, which distinguish those cells from other dermal cells and may enable supporting keratinocyte growth. In this sense, trichogenicity is probably a virtue.

Selected by M. Ohyama, Tokyo, Japan

R.P. Hill, A. Gardner, H.C. Crawford, R. Richer, A. Dodds, W.A. Owens, C. Lawrence, S. Rao, B. Kara, S.E. James and C.A. Jahoda (2013) Human hair follicle dermal sheath and papilla cells support keratinocyte growth in monolayer co-culture. Exp Dermatol Accepted manuscript online: 1 FEB 2013 doi: 10.1111/exd.12107, will be published in Vol 22, Nr. 3, March 2013

Rheinwald JG, Green H.  (1975) Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells.  Cell. Nov;6(3):331-43




Evidence for a regulatory loop between IFNγ and IL-33 in skin inflammation

Atopic dermatitis (AD) is characterized by a delicate cutaneous micromilieu of various cytokines and chemokines. Among those, interleukin-33 (IL-33), a member of the IL-1 cytokine family, has recently gained much attention due to its role in Th2 responses and damage- induced inflammation. Understanding the role of IL-33 in inflammatory diseases such as AD and allergic asthma might lead to novel treatments. Therefore, Seltmann and coworkers (2013) investigated the expression and secretion of IL-33 in resident skin cells and its impact on CD4+ T cells. The authors showed that keratinocytes and dermal fibroblasts differ in their regulation of IL-33. While in fibroblasts, TNFα, and IL-1β were the strongest inducers, IFNγ is clearly the key regulator of IL-33 in keratinocytes. Notably, keratinocytes from AD patients showed stronger responses, suggesting disturbed IL-33 regulation in these cells. Interestingly, secreted IL-33 acts on T cells and increases their production of IFNγ. The latter effect is substantially enhanced by the presence of IL-12, which is expressed in chronic AD lesions. These results suggest that IL-33 and IFNγ are closely interlinked in epidermal inflammation in AD. IFNγ induces IL-33 in keratinocytes and IL-33 acts on activated T cells to further increase the release of IFNγ, thereby driving a loop of skin inflammation towards chronic responses. In this respect, IL-33 can be linked to other IL-1 family members such as IL-1 and IL-18 and might serve as a novel target for future therapies.

Selected by J. Schauber, Munich, Germany

Seltmann J, Werfel T, Wittmann M. Evidence for a regulatory loop between IFN-γ and IL-33 in skin inflammation. Exp Dermatol. 2013 Feb; 22(2): 102-7. doi: 10.1111/exd.12076.




The Sox21 gene plays an important role for the binding of lipids on hair

Sox genes encode a family of transcription factors and are defined as containing the high mobility group box of a gene involved in sex determination called SRY, which resides on the Y-chromosome. Knocking out the Sox21 gene leads to a down-regulation of some proteins in the mouse hair cuticle, leading to improper cuticle formation. The outermost surface of the cuticle is naturally very hydrophobic due to a monomolecular layer of fatty acids, of which 18-methyleicosanoic acid (18-MEA) is a major and uniquely important component. The fatty acids are bound to the underlying protein layer through thioester linkages. Kawaminami et al (2013) now show that after knocking out the Sox21 gene the overall level and distribution of 18-MEA on the surface of hair remain largely unchanged, while a virtually comprehensive disruption of its covalent attachment occurs. Furthermore, they show that other lipids are in individual cases subject to significant changes in their concentration levels due to the knock-out. Since the bound lipids on the surface of hair fibres are known to impart beneficial properties to hair, such as hydrophobicity, low friction, protection against penetration of chemicals, and retardation of bacterial and fungal growth, they are of special importance in hair cosmetic science.

Selected by F.J. Wortmann, Manchester, United Kingdom

Kawaminami S, Breakspear S, Saga Y, Noecker B, Masukawa Y, Tsuchiya M, Oguri M, Inoue Y, Ishikawa K, Okamoto M. Deletion of the Sox21 gene drastically affects hair lipids. Exp Dermatol. 2012 Dec; 21(12): 968-70. doi: 10.1111/exd.12050


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