Get access

The Progression of Inflammation Parallels the Dermal Angiogenesis in a Keratin 14 IL-4-Transgenic Model of Atopic Dermatitis

Authors


  • This work is supported in part by NIH grants R01 AR47667, R03 AR47634, and R21 AR48438 to L.S.C., and Albert H. and Mary Jane Slepyan Fellowship Fund to R.A.M.and L.C. We thank Kathleen Green, Lisa M. Godsel, and Kaihua Wang (Department of Pathology, Northwestern University Feinberg Medical School) for their help with primary keratinocyte culture.

Address correspondence to Lawrence S. Chan, MD, UICDermatology, MC624, 808 S. Wood Street, Room 376, Chicago, IL, 60612, USA. E-mail: larrycha@uic.edu.

ABSTRACT

The role angiogenesis plays in atopic dermatitis is not well understood. The authors previously demonstrated ultrastructurally dermal microvascular angiogenesis in the IL-4-transgenic mouse model of atopic dermatitis. Here, they determine the angiogenic factors involved in dermal microvascular angiogenesis, regulatory function of inflammatory cytokines on the VEGF-A production, and microvascular permeability in this model. Computer-assisted photometric analyses for immunofluorescence-labeled CD31 demonstrated a progressive increase in blood vessel number, diameter, and percent dermal areas occupied by CD31+ vessels as the disease evolves in transgenic mice from before disease onset through early and late skin lesions. Similar findings were documented for VEGR2+ vessels. Quantification of skin angiogenic factor mRNAs showed progressive increase of transcripts of VEGF-A, but not VEGF-B, VEGF-C, or VEGF-D. ELISA showed a similar increase of VEGF-A in the serum and skin of transgenic mice. IL-6 and IFN-γ stimulated VEGF-A mRNA production in the skin and in primary keratinocytes of transgenic mice. Other skin angiogenic factors that increased included Ang-1, Ang-2, GBP-1, and VE-cadherin. Microvascular leakage began in the transgenic mouse skin before disease onset and peaked in the late stage. In conclusion, IL-6 and IFN-γ may play important roles in upregulation of VEGF-A, along with other pro-angiogenic factors, to induce dermal microvascular angiogenesis.

Ancillary