[Thioredoxin in fibroblasts of human dermis in the process of aging.]

The aim of this work was to examine the content of thioredoxin in fibroblasts of human dermis from the development until deep aging (from 20 weeks of pregnancy until 85 years old), and defining of a role of thioredoxin in age-dependent changes in the number of fibroblasts in the dermis. Thioredoxin, proliferating cells nuclear antigen (PCNA), marker of fibroblasts vimentin were detected with indirect immunohistochemical technique. Results showed that portion of fibroblasts with positive staining for thioredoxin in the dermis is increased from 20 weeks of pregnancy until 85 years old. Most expressed age related increase in portion of thioredoxin positive dermal fibroblasts (more than 9 times) is present form birth until 20 years as compared to antenatal period. General number and percent of PCNA positive fibroblasts in dermis are decreased with age with more expressed changes until 40 years old. Correlation analysis showed that age dependent decrease in the number of fibroblasts and their proliferative activity is significantly associated with increase in thioredoxin positive fibroblasts in dermis. Results allow to suggest that thioredoxin play a role in age dependent decrease in the number of fibroblasts and their proliferation in human dermis.

Immunohistological pointers to a possible role for excessive cathelicidin (LL-37) expression by apocrine sweat glands in the pathogenesis of hidradenitis suppurativa/acne inversa.

BACKGROUND: The cause of follicular occlusion, a key early event in the pathogenesis of hidradenitis suppurativa (HS), also known as acne inversa, remains unknown. OBJECTIVES: To identify changes, if any, in the antimicrobial peptide (AMP) and cytokine expression profile of HS affected human skin. METHODS: Quantitative immunohistomorphometry was used to compare the in situ protein expression of selected AMPs and cytokines in lesional HS skin from 18 patients with that in healthy skin (n = 12). The lesional skin from patients with HS was histologically subclassified based on the predominance of inflammation vs. scarring. RESULTS: Compared with healthy controls, significantly increased immunoreactivity for cathelicidin (LL-37) was noted in the apocrine sweat gland and distal outer root sheath (ORS) of the hair follicle (HF) epithelium in lesional HS skin. Immunoreactivity for LL-37, psoriasin, human ß-defensin 3 (hBD3), α-melanocyte stimulating hormone (α-MSH), macrophage migration inhibitory factor (MIF), tumour necrosis factor (TNF)-α and interleukin (IL)-8 was significantly increased in HS epidermis. LL-37 and TNF-α immunoreactivity was also increased in the dermis of lesional HS skin. In contrast, lysozyme expression was decreased in the epidermis of lesional HS skin, while that of TNF-α and IL-8 was decreased in the proximal ORS of HFs in HS lesions. These differences were most pronounced in HS with predominant inflammation. CONCLUSIONS: Our observations raise the question as to whether excessive secretion of AMPs by the skin, in particular by the apocrine sweat glands, distal HF epithelium, and epidermis, may attract inflammation and thus facilitate or promote HS development.

Uterine response to estradiol under action of chorionic gonadotropin in mice.

This work examined the effect of chorionic gonadotropin on proliferative and morphogenetic reactions in the uterus under short- and long-term estrogen treatments. Ovariectomized mice received a single injection with estradiol dipropionate (2 micro g per 100 g; subcutaneously, sc) or vehicle and injections with human chorionic gonadotropin (10 IU per 100 g; sc) or vehicle twice a day for 2 days. Other groups of animals received injections with estradiol once a week or vehicle and injections with chorionic gonadotropin or vehicle once a day for 30 days. The uteri were removed 48 h after the last estradiol or vehicle injection. In animals treated with estradiol and chorionic gonadotropin for a month, the incidence of atypical endometrial hyperplasia was significantly higher. In animals treated with estradiol and chorionic gonadotropin for 2 days or for a month, uterine mass was slightly increased, the number of mitotic cells and BrdU-labeled cells was greater in luminal epithelium, glandular epithelium, stromal and myometrial cells, whereas the expression of estrogen receptors-alpha was lower in all uterine compartments, than in control. In mice who received estradiol and chorionic gonadotropin for 2 days, levels of beta-catenin and glycogen synthase kinase-3beta in luminal and glandular epithelia were lower. In animals treated with estradiol and chorionic gonadotropin for a month, the level of beta-catenin was slightly higher, and the expression of glycogen synthase kinase-3beta was lower in luminal and glandular epithelia. Thus, chorionic gonadotropin exerts estradiol-induced proliferative and morphogenetic changes in the uterus. This action of chorionic gonadotropin is associated with decreased expression of estrogen receptors-alpha and with changes in expression of beta-catenin and glycogen synthase kinase-3beta in the uterus.