Development of atopic dermatitis in mice transgenic for human apolipoprotein C1.
Mice with transgenic expression of human apolipoprotein C1 (APOC1) in liver and skin have strongly increased serum levels of cholesterol, triglycerides, and free fatty acids, indicative of a disturbed lipid metabolism. Importantly, these mice display a disturbed skin barrier function, evident from increased transepidermal water loss, and spontaneously develop symptoms of dermatitis including scaling, lichenification, excoriations, and pruritus. Histological analysis shows increased epidermal thickening and spongiosis in conjunction with elevated numbers of inflammatory cells (eosinophils, neutrophils, mast cells, macrophages, and CD4+ T cells) in the dermis. In addition, affected mice have increased serum levels of IgE and show abundant IgE(+) mast cells in the dermis. Partial inhibition of disease could be achieved by restoration of the skin barrier function with topical application of a lipophilic ointment. Furthermore, the development of atopic dermatitis in these mice was suppressed by corticosteroid treatment. These findings in APOC1(+/+) mice underscore the role of skin barrier integrity in the pathogenesis of atopic dermatitis.
Nagelkerken
Lex
L
Department of Biosciences, TNO Quality of Life, Leiden, The Netherlands. Lex.Nagelkerken@tno.nl
Verzaal
Perry
P
Lagerweij
Tonny
T
Persoon-Deen
Carla
C
Berbee
Jimmy F P
JF
Prens
Errol P
EP
Havekes
Louis M
LM
Oranje
Arnold P
AP
D000287:Administration, Topical; D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000818:Animals; D053302:Apolipoprotein C-I / Q000235:genetics*; D003876:Dermatitis, Atopic / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D004804:Eosinophils / Q000473:pathology; D004817:Epidermis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D008099:Liver / Q000502:physiology; D008297:Male; D008407:Mast Cells / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009504:Neutrophils / Q000473:pathology; D011537:Pruritus / Q000188:drug therapy / Q000235:genetics / Q000473:pathology
D000305:Adrenal Cortex Hormones; D053302:Apolipoprotein C-I; D007073:Immunoglobulin E