Premium
Role of proteinase‐activated receptors in cutaneous biology and disease
Author(s) -
Rattenholl Anke,
Steinhoff Martin
Publication year - 2003
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.10311
Subject(s) - inflammation , keratinocyte , dermis , tryptase , biology , epidermis (zoology) , neurogenic inflammation , immunology , receptor , wound healing , substance p , mast cell , microbiology and biotechnology , cancer research , pathology , medicine , cell culture , neuropeptide , anatomy , biochemistry , genetics
The skin is the largest organ of the human body. It makes up of about 15% of the body weight. Proteinase‐activated receptor‐1 (PAR 1 ) and PAR 2 have been discovered in various constitutive or transient cells within the epidermis as well as the dermis. In fact, epidermal keratinocytes were among the first cells in which the presence of PAR 2 was reported. Several observations advanced our knowledge of PARs as regulators of skin homeostasis and disease. For example, PARs are expressed by keratinocytes and regulate growth, differentiation, pigmentation, and release of growth factors and cytokines. Mast cells release tryptase, which activates PAR 2 on keratinocytes and endothelial cells, thereby contributing to inflammation and probably allergic reactions. PAR 2 is also involved in leukocyte/endothelial interactions within the skin by modulating the functions of both microvascular endothelial cells and neutrophils. Thus, PARs may be implicated in skin pathophysiology such as wound healing, cutaneous inflammation, pruritus, tumorigenesis (e.g. melanoma, squamous cell carcinoma) and bacterial infections. Functional PAR 1 and PAR 2 were recently demonstrated on primary afferent neurons in the skin, thereby regulating neurogenic inflammation. PAR 2 agonists induce release of neuropeptides from cutaneous sensory nerves, leading to pain and itch. This review highlights the recent knowledge of PARs in cutaneous physiology and disease, and discusses the possibility of PAR agonists or antagonists as novel tools for the treatment of skin diseases. Drug Dev. Res. 59:408–416, 2003. © 2003 Wiley‐Liss, Inc.