1. ^*Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Tufts-New England Medical Center, Boston, Massachusetts, USA
2. ^†Division of Allergology and Clinical Immunology, Attikon Hospital, University of Athens School of Medicine, Athens, Greece
3. ^‡Department of Biochemistry, Tufts University School of Medicine, Tufts-New England Medical Center, Boston, Massachusetts, USA
4. ^§Department of Internal Medicine, Tufts University School of Medicine, Tufts-New England Medical Center, Boston, Massachusetts, USA
5. ^¶Department of Psychiatry, Tufts University School of Medicine, Tufts-New England Medical Center, Boston, Massachusetts, USA

Correspondence: Nikoletta Papadopoulou, Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA. Emails: nikol.papadopoulou@gmail.com, theoharis.theoharides@tufts.edu

Received 28 March 2005; Revised 27 June 2005; Accepted 28 June 2005; Published online 25 October 2005.

Abstract

Certain skin disorders, such as contact dermatitis and chronic urticaria, are characterized by inflammation involving mast cells and worsen by stress. The underlying mechanism of this effect, however, is not known. The skin appears to have the equivalent of a hypothalamic–pituitary–adrenal (HPA) axis, including local expression of corticotropin-releasing hormone (CRH) and its receptors (CRH-R). We have reported that acute stress and intradermal administration of CRH stimulate skin mast cells and increase vascular permeability through CRH-R1 activation. In this study, we investigated the expression of CRH-R1, the main CRH-R subtype in human skin, and the mast cell related gene histidine decarboxylase (HDC), which regulates the production of histamine, in normal and pathological skin biopsies. Quantitative real time PCR revealed that chronic urticaria expresses high levels of CRH-R1 and HDC as compared to normal foreskin, breast skin and cultured human keratinocytes. The lichen simplex samples had high expression of CRH-R1, but low HDC. These results implicate CRH-R in chronic urticaria, which is often exacerbated by stress.