Modulation of dermal equivalent of hypothalamuspituitary- adrenal axis in mastocytosis

Abstract

Introduction Mastocytosis is a rare disease characterized by abnormal growth and accumulation of tissue mast cells (MC) in one or more organ systems and is classified as being either cutaneous mastocytosis (CM) or systemic mastocytosis (SM). In the pioneer studies of Slominski's group, a fully functional hypothalamic-pituitary-adrenal axis equivalent has been discovered in various tissues, including skin. Aim In the present study we investigated potential involvement of hypothalamus-pituitary-adrenal (HPA) cutaneous equivalent in ongoing mastocytosis. Material and methods The expression of HPA elements: CRH, UCN1, UCN2, UCN3, CRHR1, POMC, MC1R, MC2R and NR3C1 was assessed for their mRNA level in skin biopsies of adult patients with mastocytosis and healthy donors (n = 16 and 19, respectively), while CRH, UCN1, CRHR1, ACTH and MC1R were selected for immunostaining assay (n = 13 and 7, respectively). The expression of CRH receptor 1 (CRHR1) isomers was investigated by RT-PCR. The ELISA was used for detection of cortisol, CRH, UCN and ACTH in the serum. Results The decrease in the expression of HPA element of skin equivalent was observed on both mRNA and protein levels, however quantification of immunohistochemical data was impeded due to melanin in epidermis. Furthermore, we observed infiltration of dermis with HPA elements overexpressing mononuclear cells, which is in the agreement with an in vitro study showing a high expression of HPA elements by mast cells. Conclusions Taken together, it was confirmed that the expression elements of HPA was modulated in mastocytosis, thus the potential involvement of general and local stress responses in its pathogenesis should be postulated and further investigated.

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“…In turn, IL-6 secreted by mast cells can induce CRH secretion by activating the HPA axis [ 45 ]. Interestingly, a recent study has shown deregulation of the skin equivalent of the HPA axis in cutaneous mastocytosis (neoplastic proliferation of mast cells in the skin) [ 101 ], which highlights the underlying importance of mast cells in dermal homeostasis.…”

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“…In a study by Antoniewicz et al [ 92 ], significantly elevated serum concentrations of adrenocorticotropic hormone (ACTH) were reported in patients with mastocytosis when compared to the control group. These findings support the idea of an altered skin HPA (sHPA) axis in patients with mastocytosis.…”

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“…The corticotropin-releasing hormone (CRH) is overexpressed in areas of inflammation, as well as in peripheral tissues including the skin [ 30 ], thus its dysregulation is an important factor in psoriasis pathogenesis [ 31 , 32 , 33 , 34 , 35 ]. Correspondingly, aberrant CRH-receptor 1 is linked to psoriasis [ 28 , 36 , 37 , 38 ]. The increase of CRH in psoriasis can be accompanied by the up-regulation of proopiomelanocortin (POMC) [ 39 ], melanin-concentrating hormone receptor (MCHR1), and melanocortin receptors 2, 3 and 4 [ 40 ].…”