Abstract
The transient receptor potential ankyrin 1 (TRPA1), a member of the TRP superfamily of channels, acts as ‘polymodal cellular sensor’ on primary sensory neurons where it mediates the peripheral and central processing of pain, itch, and thermal sensation. However, the TRPA1 expression extends far beyond the sensory nerves. In recent years, much attention has been paid to its expression and function in non-neuronal cell types including skin cells, such as keratinocytes, melanocytes, mast cells, dendritic cells, and endothelial cells. TRPA1 seems critically involved in a series of physiological skin functions, including formation and maintenance of physico-chemical skin barriers, skin cells, and tissue growth and differentiation. TRPA1 appears to be implicated in mechanistic processes in various immunological inflammatory diseases and cancers of the skin, such as atopic and allergic contact dermatitis, psoriasis, bullous pemphigoid, cutaneous T-cell lymphoma, and melanoma. Here, we report recent findings on the implication of TRPA1 in skin physiology and pathophysiology. The potential use of TRPA1 antagonists in the treatment of inflammatory and immunological skin disorders will be also addressed.
Highlights
Transient receptor potential (TRP) channels are polymodal cation channels primarily permeable to calcium, which work as cellular sensors implicated in many physiological functions, ranging from pure sensory activities, such as nociception and temperature sensation, and homeostatic functions, such as osmoregulation, to many other functions, such as muscle contraction and vasomotor control [1]
This review focuses on the functional role of transient receptor potential ankyrin 1 (TRPA1) in various cutaneous functions both under physiological and pathophysiological conditions
Cold-induced TRPA1 activation resulted in a specific increase in intracellular calcium in human cultured epidermal keratinocytes, much higher than that observed in dorsal root ganglion cells [84], revealing that epidermis might be more sensitive to low temperature than the peripheral nervous system, and TRPA1 expressed in keratinocytes may have a central role in thermo-sensation of the skin [85]
Summary
Transient receptor potential (TRP) channels are polymodal cation channels primarily permeable to calcium, which work as cellular sensors implicated in many physiological functions, ranging from pure sensory activities, such as nociception and temperature sensation, and homeostatic functions, such as osmoregulation, to many other functions, such as muscle contraction and vasomotor control [1]. Cold-induced TRPA1 activation resulted in a specific increase in intracellular calcium in human cultured epidermal keratinocytes, much higher than that observed in dorsal root ganglion cells [84], revealing that epidermis might be more sensitive to low temperature than the peripheral nervous system, and TRPA1 expressed in keratinocytes may have a central role in thermo-sensation of the skin [85]. These include a keratinocyte-neuron axis based on the release of thymic stromal lymphopoietin [100] and periostin [101], two AD-associated cytokines directly released by keratinocytes, and a Th2-cell-neuronal pathway based on the release of the pruritogenic cytokine IL-31 [102] These studies suggest a role of TRPA and many channel ligands have been studied, yet TRPA1 blockers remain to be used clinically as anti-itch drugs. Since evidence showed that the TRPA1 is crucially involved in the pathogenesis of AD and ACD, the pharmacological inhibition of the channel could be a valuable complementary strategy for local control of skin inflammation and pruritus observed in both diseases
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