1. ¹Laboratory of Tissue Engineering and Cutaneous Physiopathology, Istituto Dermopatico dell'Immacolata, IRCCS, via Monti di Creta 104, Rome, Italy
2. ²Laboratory of Cancer Biology and Genetics, National Cancer Institute, Center for Cancer Research, Bethesda, Maryland, USA
3. ³Section of Dermatology and Venereology, Department of Biomedical and Surgical Sciences, University of Verona, Piazzale A. Stefani 1, Verona, Italy

Correspondence: Professor Giampiero Girolomoni, Section of Dermatology and Venereology, Department of Biomedical and Surgical Sciences, University of Verona, Piazzale A. Stefani 1, Verona 37126, Italy. E-mail: giampiero.girolomoni@univr.it

Received 5 June 2007; Revised 24 August 2007; Accepted 26 September 2007; Published online 29 November 2007.

Abstract

The epidermal growth factor (EGF) family comprises multiple mediators such as transforming growth factor-, amphiregulin, heparin binding-EGF, and epiregulin, which are crucially involved in the tissue-specific proliferation/differentiation homeostasis. Typically, they act in an autocrine and paracrine manner on their specific cell membrane receptor and mount an effective reparative response to any attack to biophysical integrity. In addition, the EGFR can be activated by transactivation from a variety of G-protein-coupled receptors, integrins, and cytokine receptors, so that it acts as the major transducer of disparate cell functions, including changes in proliferation rate, cellular shape, attachment and motility, and regulation of proinflammatory activation. However, numerous experimental observations indicate that the different EGFR ligands are not redundant, but may rather provide distinct and specific contributions to keratinocyte functions. Importantly, increasing evidence now suggests that the EGFR pathway has a major impact on the inflammatory/immune reactions of the skin, in the apparent effort of enhancing innate immune defense while opposing overactivation of keratinocyte pro-inflammatory functions. This review covers the molecular mechanisms and functions activated by this major growth factor system in the regulation of keratinocyte biology and focuses on the complex contribution of EGFR signaling to the inflammatory processes in the skin.