Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disease. Bleomycin (BLM) contributes to the induction of pulmonary inflammation and fibrosis in animals. Although skin and lung tissue inflammation is closely related in the pathogenesis of allergic diseases, a proper animal model for investigating the relationship between skin and lung inflammation is lacking. Therefore, we developed a mouse model of AD with relapsing dermatitis and pulmonary fibrosis caused by the administration of allergen and BLM. The present study determined whether lung injury caused by the bronchial application of BLM would exacerbate AD-like allergic inflammation induced by 2, 4-dinitrochlorobenzene (DNCB) in NC/Nga mice. NC/Nga mice treated with BLM and DNCB had increased severity of clinical symptoms and airway hyperresponsiveness as well as increased inflammatory cell infiltration and collagen deposition in the dorsal skin and lung. Compared to normal mice, interleukin (IL)-6 and tumor necrosis factor (TNF)-α production in bronchoalveolar lavage fluid were increased in NC/Nga mice treated with both DNCB and BLM and in animals treated with DNCB alone. Administration of BLM and DNCB increased the levels of IL-4 and IL-13 production in spleen cells and eotaxin-2 mRNA expression in dorsal skin, compared to NC/Nga mice treated with DNCB alone. The total cell numbers in axillary lymph node, bronchoalveolar lavage, and thymus were increased in DNCB-BLM mice compared to those in mice treated with DNCB alone. Administration of BLM and DNCB increased the numbers of cluster of differentiation 4 (CD4)+ T cells and CD11b+granulocyte-differentiation antigen-1 (Gr-1)+ cells among peripheral blood mononuclear cells, CD4+ cells in bronchoalveolar lavage, CD4+ and B220+CD23+ B cells in the axillary lymph node, and CD4+ cells in thymus, compared to DNCB-treated mice. The number of total, CD4+, and CD11b+Gr-1+ cells in the lung were increased in both DNCB and DNCB-BLM mice. These results demonstrate that BLM aggravates allergic skin inflammation and promotes airway hyperreactivity and lung inflammation when combined with DNCB in NC/Nga mice.
Highlights
Atopic dermatitis (AD) is a chronic inflammatory skin disease that has a high prevalence among infants and children (Han et al, 2011)
Pehn values showed a greater increase in NC/Nga mice treated with both DNCB and BLM (DNCB-BLM) than in NC/Nga mice treated with DNCB alone (DNCB-Control) at doses of 25 (F-value = 5.470 and p = 0.017) and 50 mg/kg methacholine (F-value = 4.012 and p = 0.041)
AD-like symptoms were evaluated by dermatitis skin score (Method 2.6) and the skin clinical score significantly increased in both DNCB-Control and DNCB-BLM mice when compared to NC/Nga-Normal mice (F-value = 19.696 and p ≤ 0.01) (Figure 2A)
Summary
Atopic dermatitis (AD) is a chronic inflammatory skin disease that has a high prevalence among infants and children (Han et al, 2011). The skin, located on the outermost body surface, is an important interface between the host and its environment, and the skin is believed, in Oriental medicine, to be influenced by the physiological function of the lung on the body (Im et al, 2002; Glick, 2005). In Asia, AD is called ‘skin asthma,’ because so many infants and children with AD already have, or will develop, asthma (Glick, 2005). Some studies have developed animal models with localized AD induced by repeated epicutaneous sensitization with ovalbumin, and airway hyperresponsiveness to methacholine after challenge with aerosolized ovalbumin, to study the progression from AD to asthma (Spergel et al, 1998). A proper animal model for investigating the relationship among skin and lung inflammation in AD is still lacking
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