Filaggrin expression

As mentioned above, a subgroup of patients with atopic dermatitis has a filaggrin loss-of-function mutation Recently, it was shown that filaggrin expression is reduced in atopic dermatitis even in the absence of any mutation [29]. Keratinocytes differentiated in the presence of IL-4 and IL-13 exhibited significantly reduced filaggrin gene expression and neutralization of IL-4 and IL-13 improves skin barrier integrity [30]. This indicates that Th-2 lymphocytes directly contribute to the skin barrier defect in atopic dermatitis. 

Although repeated barrier disruption induces inflammation, epidermal hyperplasia, and abnormal keratinization, there are several histological differences between this model and psoriasis. Gerritsen et al.19 reported the absence of some characteristic features of psoriasis in the dry skin induced by repeated tape stripping. They also demonstrated that filaggrin expression in the model system was different from that in psoriasis. The mechanism underlying the clonical skin diseases such as psoriasis remains to be investigated. 

Howell MD, Kim BE, Gao P, Grant AV, Boguniewicz M, Debenedetto A, Schneider L, Beck LA, Barnes KC, Leung DY Cytokine modulation of atopic dermatitis filaggrin skin expression. J Allergy Clin Immunol 2007 120 150-155. 

Dale, B. A., Presland, R. B., Lewis, S. P., Underwood, R. A., and Fleckman, P. (1997). Transient expression of epidermal filaggrin in cultured cells causes collapse of intermediate filament networks with alteration of cell shape and nuclear integrity. J. Invest. Dermatol. 108, 179—187. 

Ishida-Yamamoto, A., Hashimoto, Y., Manabe, M., O Guin, W. M., Dale, B. A., and Iizuka, H. (1997). Distinctive expression of filaggrin and trichohyalin during various pathways of epithelial differentiation. Br. J. Dermatol. 137, 9-16. 

Steven, A.C., et al. 1990. Biosynthetic pathways of filaggrin and loricrin—two major proteins expressed by terminally differentiated epidermal keratinocytes. J Struct Biol 104 150. 

Katagiri, C., Sato, J., Nomura, J., and Denda, M. (2003) Changes in environmental humidity affect the water-holding property of the stratum corneum and its free amino acid content, and the expression of filaggrin in the epidermis of hairless mice. J. Dermatol. Sci. 31 29-35. 

Recently, a protein named hornerinhas been identified in mouse skin.60,61 Based on its amino acid sequence and distribution in skin it has been proposed to fulfill a similar role to profilaggrin/filaggrin in murine skin. The conditions under which it is expressed remain to be determined but it is tempting to... 

Seguchi, T. etal. Decreased expression of filaggrin in atopic skin, Arch. Dermatol. Res., 288, 442, 1996. 

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