Hypothalamic-pituitary-adrenal (HPA) axis hormones and their receptors expressed in the skin are known to function locally, but how these hormones affect the maintenance of skin homeostasis or the pathogenesis of skin diseases is not fully understood. We comprehensively reviewed the distribution and function of the central and peripheral HPA axis in various stress-related skin diseases. Previous studies have shown altered expression of central and peripheral HPA axis hormones in chronic inflammatory skin diseases and skin tumours, and that hyper-active lesional HPA axis hormones may negatively feedback to the central HPA axis and interact with some cytokines and neuropeptides, leading to symptom deterioration. This provides an evidence-based understanding of the expression of the central and peripheral HPA axis in common skin diseases and its association with disease activity.
Leukemia cutis (LC) is defined as a neoplastic leukocytic infiltration of the skin. Few clinical studies are available on recent trends of LC in Korea. The purpose of this study was to analyze the clinical features and prognosis of LC in Korea and to compare findings with previous studies. We performed a retrospective study of 75 patients with LC and evaluated the patients' age and sex, clinical features and skin lesion distribution according to the type of leukemia, interval between the diagnosis of leukemia and the development of LC, and prognosis. The male to female ratio was 2:1, and the mean age at diagnosis was 37.6 yr. The most common cutaneous lesions were nodules. The most commonly affected site was the extremities in acute myelocytic leukemia and chronic myelocytic leukemia except for acute lymphocytic leukemia. Compared with previous studies, there was an increasing tendency in the proportion of males and nodular lesions, and LC most often occurred in the extremities. The prognosis of LC was still poor within 1 yr, which was similar to the results of previous studies. These results suggest that there is a difference in the clinical characteristics and predilection sites according to type of leukemia.
LL-37 is a human cathelicidin antimicrobial peptide that is released in the skin after injury and acts to defend against infection and modulate the local cellular immune response. We observed in human dermal keloids that fibrosis was inversely related to the expression of cathelicidin and sought to determine how LL-37 influenced expression of types I and III collagen genes in dermal fibroblasts. At nano-molar concentrations, LL-37 inhibited baseline and transforming growth factor-β-induced collagen expression. At these concentrations, LL-37 also induced phosphorylation of extracellular signal-regulated kinase (ERK) within 30 minutes. Activation of ERK, and the activation of a G-protein-dependent pathway, was essential for inhibition of collagen expression as pertussis toxin or an inhibitor of ERK blocked the inhibitory effects of LL-37. c-Jun N-terminal kinase and p38 mitogen-activated protein kinase inhibitors did not alter the effects of cathelicidin. Silencing of the Ets-1 reversed inhibitory effects of LL-37. Taken together, these findings show that LL-37 can directly act on dermal fibroblasts and may have antifibrotic action during the wound repair process.
Psychological stress is known to aggravate inflammatory skin diseases such as atopic dermatitis, psoriasis and contact sensitivity by altering the cellular constituents of the immune system. The skin appendages function dually as prominent targets and sources of the peripheral corticotropin-releasing hormone-proopiomelanocortin (CRH-POMC) axis. In this study, we examined the expression level of CRH-POMC axis constituents in psoriasis, a well-known stress-related inflammatory skin disease. The 15 psoriasis patients and six normal controls were retrospectively selected after extensive review of their clinical records and skin biopsy specimens. We immunohistochemically analysed the expressivity of CRH, adrenocorticotrophic hormone (ACTH) and alpha-melanocyte-stimulating hormone (alpha-MSH) in various types of psoriatic lesions and control skin. A significant increase of CRH expression was observed in psoriatic lesions, which involved the entire epidermis (upper layer in particular), hair follicles and sweat glands compared with controls. Expression of ACTH and alpha-MSH was clearly stimulated in a subset of psoriasis patients compared with controls, but on the whole, lacked statistical significance. The immunoreactivity of CRH, ACTH and alpha-MSH in psoriasis was not dependent on its clinical subtype, duration or number of previous treatments. Compared with the definite increase of CRH expression in psoriasis, the expression of the POMC peptides was heterogenous with no overall significance. From the findings, we suggest that CRH, a key stress hormone, may play an important role in the pathomechanism of psoriasis.
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