Friess M, Engelhardt P, Dobbelaere D, Zurbriggen A, Gröne A
Institut für Tierpathologie, Universität Bern, 3001 Bern, Switzerland.
J Comp Pathol. 2005 Jan;132(1):82-9. doi: 10.1016/j.jcpa.2004.07.004.
Infection of canine footpads with the canine distemper virus (CDV) can cause massive epidermal thickening (hard pad disease), as a consequence of increased proliferation of keratinocytes and hyperkeratosis. Keratinocytes of canine footpad epidermis containing detectable CDV nucleoprotein antigen and CDV mRNA were shown previously to have increased proliferation indices. Because various proteins that play a role in the proliferation of epidermal cells are viral targets, the potential participation of such proteins in CDV-associated keratinocyte proliferation was investigated. Transforming growth factor-alpha (TGF-alpha), cell cycle regulatory proteins p21, p27 and p53, and nuclear factor (NF)-kappaB transcription factor components p50 and p65 were studied in the footpad epidermis from the following groups of dogs inoculated with CDV: group 1, consisting of seven dogs with clinical distemper and CDV in the footpad epidermis; group 2, consisting of four dogs with clinical distemper but no CDV in the footpad epidermis; group 3, consisting of eight dogs with neither clinical distemper nor CDV in the footpad epithelium. Group 4 consisted of two uninoculated control dogs. The expression of TGF-alpha, p21, p27 and p53, and p50 in the basal layer, lower and upper spinous layers, and in the granular layer did not differ statistically between CDV-positive (group 1) and CDV-negative (groups 2-4) footpad epidermis. However, there were differences in the levels of nuclear and cytoplasmic p65 expression between group 1 dogs and the other three groups. Thus, footpads from group 1 dogs had more keratinocytes containing p65 in the cytoplasm and, conversely, fewer nuclei that were positive for p65. These findings indicate that p65 translocation into the nucleus is reduced in CDV-infected footpad epidermis. Such decreased translocation of p65 may help to explain increased keratinocyte proliferation in hard pad disease and suggests interference of CDV with the NF-kappaB pathway.
犬瘟热病毒（CDV）感染犬脚垫可导致大量表皮增厚（硬垫病），这是角质形成细胞增殖增加和角化过度的结果。先前已表明，含有可检测到的CDV核蛋白抗原和CDV mRNA的犬脚垫表皮角质形成细胞具有增加的增殖指数。由于在表皮细胞增殖中起作用的各种蛋白质是病毒的靶标，因此研究了这些蛋白质在CDV相关角质形成细胞增殖中的潜在参与情况。在接种CDV的以下几组犬的脚垫表皮中研究了转化生长因子-α（TGF-α）、细胞周期调节蛋白p21、p27和p53以及核因子（NF）-κB转录因子成分p50和p65：第1组，由七只患有临床犬瘟热且脚垫表皮中有CDV的犬组成；第2组，由四只患有临床犬瘟热但脚垫表皮中无CDV的犬组成；第3组，由八只脚垫上皮既无临床犬瘟热也无CDV的犬组成。第4组由两只未接种的对照犬组成。在CDV阳性（第1组）和CDV阴性（第2 - 4组）的脚垫表皮之间，TGF-α、p21、p27、p53和p50在基底层、下棘层和上棘层以及颗粒层中的表达在统计学上没有差异。然而，第1组犬与其他三组犬之间在核和细胞质p65表达水平上存在差异。因此，第1组犬的脚垫中有更多细胞质中含有p65的角质形成细胞，相反，p65阳性的细胞核较少。这些发现表明，在CDV感染的脚垫表皮中p65向细胞核的易位减少。p65这种易位减少可能有助于解释硬垫病中角质形成细胞的增殖增加，并提示CDV干扰了NF-κB途径。
