The progression of inflammation parallels the dermal angiogenesis in a keratin 14 IL-4-transgenic model of atopic dermatitis.
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-gamma 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-gamma may play important roles in upregulation of VEGF-A, along with other pro-angiogenic factors, to induce dermal microvascular angiogenesis.
Chen
Lin
L
Department of Dermatology, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Marble
Deborah J
DJ
Agha
Rania
R
Peterson
Jennifer D
JD
Becker
Robert P
RP
Jin
Tianquan
T
Li
Jianxun
J
Chan
Lawrence S
LS
D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D020405:Dermis / Q000098:blood supply* / Q000166:cytology / Q000502:physiology; D004195:Disease Models, Animal; D019204:GTP-Binding Proteins / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics* / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D053547:Keratin-14 / Q000235:genetics* / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D008833:Microcirculation / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D015854:Up-Regulation / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000099152:Cadherin 5
D000803:Angiotensin I; D000804:Angiotensin II; D015703:Antigens, CD; D015820:Cadherins; D019204:GTP-Binding Proteins; D007371:Interferon-gamma; D015847:Interleukin-4; D015850:Interleukin-6; D053547:Keratin-14; D042461:Vascular Endothelial Growth Factor A; D000099152:Cadherin 5; C490288:Gbp2b protein, mouse; C507446:Krt14 protein, mouse; C467480:vascular endothelial growth factor A, mouse