interleukin-8 and Keratosis

A subgroup of the transient receptor potential (TRP) channels, including vanilloid 1 (TRPV1), TRPV2, TRPV3, TRPV4, and TRP ankyrin 1 (TRPA1), is expressed in cutaneous peptidergic somatosensory neurons, and has been found in skin non-neuronal cells, such as keratinocytes. Different cancer cells express TRPs, where they may exert either pro- or antitumorigenic roles. Expression and function of TRPs in skin cancers have been, however, poorly investigated. Here, we have studied the distribution and expression of TRPs by immunohistochemistry and messenger RNA (mRNA) in human healthy skin and human keratinocytic tumors, including intraepidermal proliferative disorders (solar keratosis (SK) and Bowen's disease), and non-melanoma skin cancer (NMSC; basal cell and squamous cell carcinomas). Similar TRPV1, TRPV2, and TRPV3 staining was found in keratinocytes from healthy and tumor tissues. TRPA1 staining was increased solely in SK samples. However, the marked TRPV4 staining and TRPV4 mRNA expression, observed in healthy or inflamed skin, was abrogated both in premalignant lesions and NMSC. In a human keratinocyte cell line (HaCaT), TRPV4 stimulation released IL-8, which in turn downregulated TRPV4 expression. Selective reduction in TRPV4 expression could represent an early biomarker of skin carcinogenesis. Whether the cytokine-dependent, autocrine pathway that results in TRPV4 downregulation contributes to NMSC mechanism remains to be determined.

Topics: Adult; Aged; Aged, 80 and over; Autocrine Communication; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Down-Regulation; Female; Gene Expression Regulation, Neoplastic; HEK293 Cells; Humans; Interleukin-8; Keratinocytes; Keratosis; Male; Middle Aged; Precancerous Conditions; Skin Neoplasms; Tissue Banks; TRPV Cation Channels

Psoriatic scale extracts contain a unique chemotactic peptide fraction that is likely to be involved in the induction of rhythmic transepidermal leukocyte chemotaxis. Recent studies have identified the presence of two unrelated chemotactic peptides in this fraction, ie, C5a/C5a des Arg and interleukin 8 (IL-8), and its related cytokines. To investigate their relative contribution to the transepidermal leukocyte migration as well as their interrelationship in psoriatic lesions, we have quantified concentrations of immunoreactive C5a/C5a des Arg and IL-8 in psoriatic lesional scale extracts and those from related sterile pustular dermatoses such as subcorneal pustular dermatosis and pustulosis palmaris et plantaris.. The concentrations of C5a/C5a des Arg and IL-8 were more significantly increased in the horny-tissue extracts from lesional skin than in those from noninflammatory orthokeratotic skin (P < .01). The increase of C5a/C5a des Arg concentration was specific to the lesional scale extracts, but showed a rather wide range of variation. By contrast, IL-8 concentration, although consistently increased in the lesional scale extracts, was also moderately increased even in noninflammatory scale extracts prepared from ichthyosis vulgaris. The elevation of IL-8 levels in psoriatic lesions was also confirmed by measuring their levels in cutaneous tissue fluid samples collected from suction blisters. However, unexpectedly, some control samples obtained from normal skin also showed a moderate increase in the IL-8 level. Neutrophil chemotactic activity correlated significantly only with the levels of C5a/C5a des Arg in the scales (P < .05). No such significant correlation was found between chemotactic activity and IL-8 or between C5a/C5a des Arg and IL-8.. Based on these results, we speculate that, although IL-8 may exert a synergistic effect with C5a/C5a des Arg in the induction of transepidermal leukocyte chemotaxis, it constitutes a proinflammatory cytokine that is involved in the production of the persistent inflammatory changes characterized by a T-lymphocyte infiltration. In contrast, C5a/C5a des Arg seems to be generated only in the inflammatory lesional skin under specific circumstances that preferentially favor complement activation and also seems to play a major role in the induction of cyclic transepidermal leukocyte chemotaxis from "squirting papillae."

Topics: Adolescent; Adult; Chemotactic Factors; Chemotaxis, Leukocyte; Complement C5a, des-Arginine; Female; Humans; Interleukin-8; Keratosis; Male; Middle Aged; Neutrophils; Psoriasis; Skin