Corticotropin-releasing hormone affects cytokine production in human HaCaT keratinocytes

doi:10.1016/S0024-3205(01)01476-X

Life Sciences

Volume 70, Issue 9, 18 January 2002, Pages 1013-1021

https://doi.org/10.1016/S0024-3205(01)01476-X Get rights and content

Abstract

CRH cutaneous expression is significantly enhanced after exposure to various stimuli (Physiol Rev 2000, 80;979–1020). We evaluated the effect of CRH on cytokine production in HaCaT keratinocytes, a cell line shown to express CRH receptors coupled to cAMP activation and calcium-dependent transmission pathways. It is demonstrated for the first time that exogenously added CRH stimulates production of IL-6 and IL-11. It also inhibits production of IL-1beta and does not affect TNF-alpha production. Our results indicate that CRH function(s) during cutaneous stress may be mediated by differential effects on cytokine production.

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Citation Excerpt :
In addition, CRH acts as growth factor, stimulating proliferation of dermal fibroblasts and melanocytes.30,31 Another important effect of CRH in keratinocytes is the stimulation of the production of proinflammatory cytokines.32 The prominent pituitary hormones found in the skin are POMC and the neuropeptides resulting from its cleavage.
Although scientific articles mention the impact of psychological stress on skin diseases, few review the latest research on factors involved in this correlation. The skin actively responds to psychological stress, with involvement of skin immune cells, hormones, neurotransmitters. Skin immune cells actively regulate tissue inflammation with their proinflammatory and anti-inflammatory effects. Stress-induced skin reactions primarily include cytokine secretion (e.g. interleukin-6, interleukin-1, interferon-γ) and activation of skins peripheral corticotropin-releasing hormone (CRH)-proopiomelanocortin (POMC)-adrenocorticotropic hormone (ACTH)-corticosteroids axis, which leads to acute/chronic secretion of corticosteroids in the skin.
This narrative review presents the current knowledge and latest findings regarding the impact of psychological stress on skin diseases, including information concerning psychoneuroimmune factors in stress-induced skin responses. Recent articles published in English available through the PubMed database and other prominent literature are discussed.
Stress mediators, including cortisol, ACTH, and CRH from hypothalamus-pituitary-adrenal axis activation, induce various skin immune responses. Skin cells themselves can secrete these hormones and participate in skin inflammation. Thus, the local skin CRH-POMC-ACTH-corticosteroids axis plays a prominent role in stress-induced responses. Also, keratinocytes and fibroblasts produce hypothalamic and pituitary signal peptides and express receptors for them (CRH with receptors and POMC degradation peptides with melanocortin receptors), which allows them to respond to CRH by activating the POMC gene, which is then followed by ACTH and subsequently corticosteroids excretion. In addition, keratinocytes can express receptors for neurotransmitters (e.g. adrenaline, noradrenaline, dopamine, histamine, acetylcholine), neurotrophins, and neuropeptides (e.g. substance P, nerve growth factor), which are important in linking psychoneuroimmunologic mechanisms.
Psychoneuroimmunology provides an understanding that the skin is target and source of stress mediators. This locally expressed complex stress-induced network has been confirmed as active in many skin diseases (e.g. vulgar psoriasis, atopic dermatitis, chronic urticaria, human papillomavirus infections/warts, hair loss, acne). Skin reactions to stress and its influence on skin diseases may have implications for disease severity and exacerbation frequency, given the effect of locally secreted corticosteroids and other mediators that affect skin integrity, inflammation, and healing potential. Studies have also shown that introducing psychiatric treatment (drugs or psychotherapeutic methods) can have positive effects on dermatologic diseases influenced by psychological stress exposure. We hope this review provides clinicians and scientists with more complete background for further research in this field of skin psychoneuroimmunology.
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Citation Excerpt :
Since, IL-1 was demonstrated as one of the principal mediators of LPS induced toxicity on the basis of IL-1 receptor blockade experiments (Alexander et al., 1991). It is evident that local CRF downregulates IL-1β, IL-2, and IL-18 in keratocytes (Zbytek et al, 2003, 2002). However, all of those cytokines are known to be overexpressed in endotoxin stress (Carter et al., 1998).
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Original articlesCorticotropin-releasing hormone affects cytokine production in human HaCaT keratinocytes

Abstract

Original articles
Corticotropin-releasing hormone affects cytokine production in human HaCaT keratinocytes