Molecular Mechanism of Atopic Dermatitis Induction Following Sensitization and Challenge with 2,4-Dinitrochlorobenzene in Mouse Skin Tissue

Abstract

Laboratory animal models have been developed to investigate preventive or therapeutic effect of medicinal products, or occurrence or progression mechanism of atopic dermatitis (AD), a pruritic and persistent inflammatory skin disease. The murine model with immunologic phenomena resembling human AD was introduced, which demonstrated skewedness toward predominance of type-2 helper T cell reactivity and pathophysiological changes similar as human AD following 2,4-dinitrochlorobenzene (DNCB) sensitization and challenge. Molecular mechanism on the DNCB-mediated AD was further evaluated. Skin tissues were collected from mice treated with DNCB, and each tissue was equally divided into two sections; one for protein and the other for mRNA analysis. Expression of filaggrin, an important protein for keratinocyte integrity, was evaluated through SDS-PAGE. Level of mRNA expression for cytokines was determined through semi-quantitative reverse transcriptase polymerase chain reaction. Expression of filaggrin protein was significantly enhanced in the mice treated with DNCB compared with the vehicle (acetone : olive oil = 4 : 1 mixture) treatment group or the normal group without any treatment. Level of tumor necrosis factor-alpha and interleukin-18 mRNA expression, cytokines involved in activity of type-1 helper T (TH1) cell, was significantly downregulated in the AD group compared with other control groups. These results suggest that suppression of TH1 cell-mediated immune response could be reflected into the skin tissue of mice treated with DNCB for AD induction, and disturbance of keratinocyte integrity might evoke a compensatory mechanism.

Apremilast Normalizes Gene Expression of Inflammatory Mediators in Human Keratinocytes and Reduces Antigen-Induced Atopic Dermatitis in Mice

“…There are multiple models of AD in the mouse, using various antigens such as fluorescein isothiocyanate (FITC) [32] and dinitrochlorobenzene (DNCB) [33]. These models rely on a sensitization period wherein the antigen is applied directly to the skin of the abdomen or flank to allow dendritic cells to process and present the antigen to reactive T cells, which clonally expand and produce Th2 and Th17 cytokines and chemokines.…”

“…The goals of these studies were to (a) assess the expression of PDE4 isoforms in the epidermis of healthy subjects and patients with AD; (b) determine the direct effects of PDE4 inhibition on Th2 (IL-4)-and Th17 (IL-17)-induced gene expression in primary adult human epidermal keratinocytes (HEKa); and (c) assess the effects of apremilast in two mouse models of AD using two antigens, FITC [32] and DNCB [33].…”

Therapeutic effects of topically-administered guar gum nanoparticles in oxazolone-induced atopic dermatitis in mice

“…Atopic dermatitis is quite a common disease, with a prevalence of about 20% in developing countries [21]. To date, therapy for AD includes steroids and certain inhibitors, which are known to have adverse effects.…”

“…The ears of the mice in the Oxazolone group were topically sensitized with 40 µl of 0.8% Oxazolone (Sigma-Aldrich, St. Louis, MO), dissolved in acetone (SRL, India) on day 0, and challenged with 0.4% Oxa on days 7,10,12,14,17,19,21,23, 25 and 27. The topical administration was done using a microtip attached with a micropipette (Tarsons, Inc.).…”

Ameliorative effects of sea buckthorn oil on DNCB induced atopic dermatitis model mice via regulation the balance of Th1/Th2

“…AD affects nearly 20% of children and 3% of adults worldwide and the incidents become higher and higher [5]. Although the pathogenesis of AD is not explicit utterly, genetic risk, environmental factors, skin barrier dysfunction and immune dysregulation are thought to play important roles during the pathogenesis of AD [5][6][7][8]. As for immune dysregulation, Th2 skewing seems to be the key point of AD pathogenesis [9,10].…”