Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by severe itching, erythema and edema resistant to anti-histamine therapy. Vascular endothelial growth factor (VEGF) is a potent agent that causes hyperpermeability of blood vessels and endothelial cell proliferation, and might be involved in the persisting erythema and edema in AD. In this study, we used extraction of stratum corneum with physiological saline to detect VEGF produced in the lesions of AD. Biological activity of VEGF was assayed by proliferation of cultured human umbilical vein endothelial cells in vitro. As a result, we found that the amount of VEGF produced in lesional scales was approximately 25 times higher than that in normal stratum corneum. Moreover, VEGF 121 isoform that exclusively induces hyperpermeability of blood vessels was a predominant component in the lesional scales suggesting that this factor plays an important role in the persisting erythema and edema in the AD lesions.
This is a preview of subscription content, log in via an institution to check access.
References
Ballaun C, Weninger W, Uthman A, Weich H, Tschachler E (1995) Human keratinocytes express the three major splice forms of vascular endothelial growth factor. J Invest Dermatol 104:7–10
Barnhill RL, Parkinson EK, Ryan TJ (1984) Supernatants from cultured human epidermal keratinocytes stimulate angiogenesis. Br J Dermatol 110:273–281
Brown LF, Olbricht SM, Berse B, Jackman RW, Matsueda G, Tognazzi KA, Manseau EJ, Dvorak HF, Water LVD (1995) Overexpression of vascular permeability factor (VPF/VEGF) and its endothelial cell receptors in delayed hypersensitivity skin reactions. J Immunol 154:2801–2807
Detmar M, Brown LF, Claffey KP, Yeo KT, Kocher O, Jackman RW, Berse B, Dvorak HF (1994) Overexpression of vascular permeability factor/vascular endothelial growth factor and its receptors in psoriasis. J Exp Med 180:1141–1146
Detmar M, Yeo KT, Nagy JA, Water LVD, Brown LF, Berse B, Elicker BM, Ledbetter S, Dvorak HF (1995) Keratinocyte-derived vascular permeability factor (vascular endothelial growth factor) is a potent mitogen for dermal microvascular endothelial cells. J Invest Dermatol 105:44–50
Dvorak HF, Detmar M, Claffey KP, Nagy JA, van de Water L, Senger DR (1995) Vascular permeability factor/vascular endothelial growth factor: an important mediator of angiogenesis in malignancy and inflammation. Int Arch Allergy Immunol 107:233–235
Ferrara N, Houck K, Jakeman L, Leung DW (1992) Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocr Rev 13:18–32
Hanifin JM, Butler JM, Chan SC (1985) Immunopharmacology of the atopic diseases. J Invest Dermatol 85:161s–164s
Horsmanheimo L, Harvima IT, Järvikallio A, Harvima RJ, Naukkarinen A, Horsmanheimo M (1994) Mast cells are one major source of interleukin-4 in atopic dermatitis. Br J Dermatol 131:348–353
Houck KA, Ferrara N, Winer J, Cachianes G, Li B, Leung DW (1991) The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol Endocrinol 5:1806–1814
Johnson HH Jr, Deoreo GA, Lascheid WP, Mitchell F (1960) Skin histamine levels in chronic atopic dermatitis. J Invest Dermatol 34:237–238
Küsters B, de Waal RMW, Wesseling P, Verrijp K, Maass C, Heerschap A, Barentsz JO, Sweep F, Ruiter DJ, Leenders WPJ (2003) Differential effects of vascular endothelial growth factor A isoforms in a mouse brain metastasis model of human melanoma. Cancer Res 63:5408–5413
Lei J, Jiang A, Pei D (1998) Identification and characterization of a new splicing variant of vascular endothelial growth factor: VEGF 183. Biochem Biophys Acta 1443:400–406
Mihm MC, Soter NA, Dvorak HF, Austen KF (1976) The structure of normal skin and the morphology of atopic eczema. J Invest Dermatol 67:305–312
Morita E, Kameyoshi Y, Hiragun T, Mihara S, Yamamoto S (2001) The C–C chemokines, RANTES and eotaxin, in atopic dermatitis. Allergy 56:194–195
Morita E, Hiragun T, Mihara S, Kaneko S, Matsuo H, Zhang Y, Dekio S (2004) Determination of thymus and activation-regulated chemokine (TARC)-contents in scales of atopic dermatitis. J Dermatol Sci 34:237–240
Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z (1999) Vascular endothelial growth factor (VEGF) and its receptors. FASEB J 13:9–22
Poltorak Z, Cohen T, Sivan R, Kandelis Y, Spira G, Vlodavsky I, Keshet E, Neufeld G (1997) VEGF 145, a secreted vascular endothelial growth factor isoform that binds to extracellular matrix. J Biol Chem 272:7151–7158
Prose PH, Sedlis E (1960) Morphologic and histochemical studies of atopic eczema in infants and children. J Invest Dermatol 34:149–165
Ruzicka T, Simmet T, Peskar BA, Ring J (1986) Skin levels of arachidonic acid-derived inflammatory mediators and histamine in atopic dermatitis and psoriasis. J Invest Dermatol 86:105–108
Ryan TJ (1970) Factors influencing the growth of vascular endothelium in the skin. Br J Dermatol 82(suppl 5):99–111
Senger DR, Perruzzi CA, Feder J, Dvorak HF (1986) A highly conserved vascular permeability factor secreted by a variety of human and rodent cell lines. Cancer Res 46:5629–5632
Tagami H, Ofuji S (1976) Leukotactic properties of soluble substances in psoriasis scale. Br J Dermatol 95:1–8
Tischer E, Mitchell R, Hartman T, Silva M, Gospodarowicz D, Fiddes JC, Abraham JA (1991) The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem 266:11947–11954
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zhang, Y., Matsuo, H. & Morita, E. Increased production of vascular endothelial growth factor in the lesions of atopic dermatitis. Arch Dermatol Res 297, 425–429 (2006). https://doi.org/10.1007/s00403-006-0641-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00403-006-0641-9