Inflammation-driven dermal lymphangiogenesis in atopic dermatitis is associated with CD11b+ macrophage recruitment and VEGF-C up-regulation in the IL-4-transgenic mouse model.

Microcirculation : the Official Journal of the Microcirculatory Society, Inc
Vivian Y ShiLawrence S Chan

Abstract

To investigate the presence and extent of inflammatory lymphangiogenesis in AD and determine the role of IL-4 in lymphatic proliferation in both K14-IL-4 Tg mouse model of AD and cultured human epidermal cells. Skin tissues from Tg mice were collected for immunostaining against PDPN, LYVE-1, CD11b and VEGF-C. The regulation of specific lymphatic biomarkers and growth factors were determined using qPCR and Western Blot analyses. Dermal lymphatic uptake and drainage were assessed using intradermal EB dye micro-injections. Total RNA from IL-4-stimulated HaCaT cells was analyzed in a PCR array to evaluate the regulation of lymphangiogenic-related genes. Prominent dermal microvascular lymphangiogenesis occurs in the Tg mice, characterized by a significant increase in number and caliber of the vasculature. The extent of both lymphatic proliferation and drainage parallels the progression of lesion severity, as does the up-regulation of pro-lymphangiogenic factors VEGF-C, VEGFR-3, ANG-1, and ANG-2. IL-4-stimulated HaCaT cells express high levels of MCP-1, a strong macrophage chemo-attractant. Additionally, Tg mice show significantly increased number of dermal CD11b+ macrophages expressing VEGF-C in the skin. Our results provide the fir...Continue Reading

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Atopic Dermatitis

Atopic dermatitis is a chronic inflammatory genetically determined disease of the skin marked by increased ability to form reagin (IgE), with increased susceptibility to allergic rhinitis and asthma, and hereditary disposition to a lowered threshold for pruritus. Discover the latest research on atopic dermatitis here.