Rosacea can be categorized into four different subtypes (Wilkin et al, 2002
; Elewski et al, 2011
). Subtype I, erythematotelangiectatic rosacea (ETR), involves flushing - often after trigger factors such as temperature changes, spicy food, hot beverages, UV exposure, exercising, emotional stress, or alcohol - facial erythema and telangiectasia. Subtype II, papulopustular rosacea (PPR), is associated with papules and/or pustules in addition to erythema. Subtype III, phymatous rosacea (PhR), is characterized by skin fibrosis and glandular hyperplasia leading to phymata, mainly rhinophyma. Another differentiated subtype is ocular rosacea.
Etiopathological factors discussed are dysfunction of the innate immune system, dermal matrix degeneration, chemical irritants, or microbial organisms (Yamasaki and Gallo, 2009
; Zhang et al., 2011a
). Because the symptoms of rosacea such as vasodilation, flushing, increased skin sensitivity, and lower pain thresholds (Guzman-Sanchez et al., 2007
) are caused by neuromediators (e.g., PACAP (pituitary adenylate cyclase-activating polypeptide); Seeliger et al., 2010
), the involvement of the skin nervous system can be anticipated. As classical neuronal receptors can also be expressed by non-neuronal cells such as keratinocytes, endothelial cells, and immune cells, a dysregulation of these receptors on non-neuronal cells in rosacea has to be considered as well.
TRPV (transient receptor potential vanilloid subfamily) receptors are a subgroup of the heterogeneous TRP cation channels with markedly diverse functions. The TRPV subfamily consists of four nonselective cation channels (TRPV1, TRPV2, TRPV3, and TRPV4) and two highly Ca2+ selective channels (TRPV5 and TRPV6; Nilius et al., 2007
; Aubdool and Brain, 2011
TRPV1 is expressed on neuronal cells and has an important role in nociception (Basbaum et al., 2009
) and neurogenic inflammation (Roosterman et al., 2006
). In addition, in non-neuronal cells, e.g., keratinocytes, TRPV1 is discussed to be expressed (Pecze et al., 2008
). It is activated by capsaicin (‘‘spicy food’’), heat (>42 °C), or under inflammatory conditions. TRPV2 was found on neuropeptide-positive C-fibers and many other non-neuronal cells, e.g., keratinocytes (Axelsson et al., 2009
) and macrophages (Link et al., 2010
). It is suggested to have a role in innate immunity, inflammation, nociception, and sensing of noxious heat. TRPV3 is localized on neuronal tissue, skin, and blood vessels (Earley et al., 2010
). TRPV3 is activated by innocuous warm temperatures (32–39 °C) and is involved in thermosensation and keratinocyte differentiation (Cheng et al., 2010
). TRPV4 is widely spread on neuronal and nonneuronal cells, including keratinocytes and endothelium. It is activated by moderate heat (24–34 °C), hypotonic cell swelling, and inflammatory metabolites. It may serve as an osmoreceptor, promote vasodilation, and cause mechanical and inflammation-evoked hyperalgesia (Vennekens et al., 2008
According to the fact that TRPV channels can be activated by typical trigger factors of rosacea, these receptors may have a role in the pathophysiology of this disease by ‘‘sensing’’ exogenous and endogenous trigger factors in the skin. Therefore, the aim of this study was to (1) investigate the distribution of TRPV2, TRPV3, and TRPV4 in non-neuronal cells of rosacea patients by immunohistochemistry and double immunoflourescence, (2) perform a semiquantitative analysis of the immunohistochemical data, (3) determine the expression levels of TRPV1, TRPV2, TRPV3, and TRPV4 in rosacea-affected skin by quantitative real-time PCR (qRT-PCR), and (4) compare these results with skin tissues from healthy donors and patients with lupus erythematosus (LE).