Cutaneous expression of β-defensins in atopic dogs

Abstract

The innate immune system protects the skin against microbial pathogens by the production of a subclass of cationic antimicrobial peptides,the β-defensins. The expression of canine β-defensin 1 and canine β-defensin 103, two of the 42 known canine β-defensin genes has been confirmed in the skin of dogs. An impaired expression and mobilization of these β-defensins has been demonstrated in the skin of humans with the chronic allergic skin disorder atopic dermatitis, explaining the high ratio of secondary bacterial skin infections found in these patients. However, in dogs the role of β-defensins in canine atopic dermatitis, a disease with a similar immunopathogenesis as human atopic dermatitis, has not been characterised. The clinically observed high frequency of secondary infections with Staphylococcus intermedius and Malassezia pachydermatis in atopic dogs indicates a defective epidermal barrier. Therefore, the tissue expression of 12 β-defensins was investigated with semi-quantitative PCR in the skin,lung, duodenum, colon, liver, testis, kidney, spleen, lymph nodes, bone marrow and peripheral blood mononuclear cells. This gene-expression study of canine β-defensins (cBDs) in 11 tissues revealed a variable expression of cBDs in different organs of the dog. To investigate the expression of cBD1 and cBD103 in healthy and atopic dogs, full thickness skin biopsy specimens from ten atopic dogs (non-lesional and lesional) and seven healthy dogs were examined with real-time PCR. A significant 12-fold increased expression of cBD1 was detected in lesional atopic skin compared to healthy skin. A significant 5-fold increased expression of cBD1 was found in non-lesional atopic skin compared to healthy skin. Furthermore, nonlesional atopic skin showed a significant 3-fold decreased expression of cBD103 compared to healthy skin. A significant higher expression of S100A8, a known marker for atopic dermatitis in both human and dogs, was confirmed in canine atopic skin with real-time PCR. With the use of immunohistochemistry, the presence of cBD103 peptide was found in the epidermis, hair follicles and sebaceous glands. The present study demonstrates, for the first time, an altered expression of cBD1 and cBD103 in the skin of atopic dogs, providing evidence for a defect in a part of the innate immune response of dogs with atopic dermatitis.