Keratinocyte dysfunction in vitiligo epidermis: cytokine microenvironment and correlation to keratinocyte apoptosis
Silvia Moretti1, Paolo Fabbri1, Gianna Baroni2, Samantha Berti1, Daniele Bani3, Emilio Berti4, Romina Nassini5, Torello Lotti1 and Daniela Massi2
1Department of Dermatological Sciences, University of Florence, Florence, Italy, 2Department of Human Pathology and Oncology, University of Florence, Florence, Italy, 3Department of Anatomy, Histology and Forensic Medicine (Histology Section), University of Florence, Florence, Italy, 4Department of Medicine, Prevention and Biotechnology, University of Milan-Bicocca, Milan, Italy and 5Department of Preclinical and Clinical Pharmacology, University of Florence, Florence, Italy.
Offprint requests to: Prof. Daniela Massi, Dipartimento di Patologia Umana ed Oncologia, Università degli Studi di Firenze, Viale G.B. Morgagni 85, 50134 Firenze, Italy. e-mail: daniela.massi@unifi.it
Summary. Vitiligo is a skin disorder characterized by loss of functional melanocytes. Keratinocytes contribute to melanocyte homeostasis, and keratinocyte alteration may play a role in melanocyte dysfunction in vitiligo. In particular, the release of melanogenic mediators and the level of functioning keratinocytes may affect melanocyte dysfunction in vitiligo epidermis. Keratinocyte-derived mediators involved in pigmentation, analysed by in situ hybridization, and epidermal apoptosis, detected by TUNEL assay and electron microscopy, were evaluated in lesional and perilesional skin biopsies from 15 patients with active vitiligo and in 5 control subjects. Among the melanogenic mediators, stem cell factor (SCF) and endothelin-1 (ET-1) mRNA were significantly reduced in lesional as compared to perilesional epidermis, whereas no difference was observed in mRNA of basic fibroblastic growth factor (bFGF) and granulocyte-monocyte colony stimulating factor (GM-CSF). The expression of mRNA for tumor necrosis factor (TNF)-α and interleukin-6 (IL-6), two pro-inflammatory cytokines with an inhibitory effect on pigmentation, was increased in the epidermis from vitiligo biopsies, whereas their expression was practically undetectable in the skin of control subjects. Apoptotic keratinocytes were more abundant in lesional vs. perilesional skin of vitiligo patients and were absent in the epidermis of control subjects. Changes in expression of keratinocyte-derived mediators observed in the present study are consistent with their differential functions in melanocyte regulation. In particular, increased TNF-α could contribute to keratinocyte apoptosis, which results in reduced release of melanogenic cytokines and ultimately in melanocyte disappearance. Histol Histopathol 24, 849-857 (2009)
Key words: Vitiligo, Apoptosis, Keratinocytes, Cytokines
DOI: 10.14670/HH-24.849