Blockade of the EGF receptor induces a deranged chemokine expression in keratinocytes leading to enhanced skin inflammation

Francesca Mascia, Valentina Mariani, Giampiero Girolomoni, Saveria Pastore

Research output: Contribution to journalArticle


During inflammatory skin disorders such as psoriasis, atopic dermatitis, and allergic contact dermatitis, epidermal keratinocytes overexpress large amounts of soluble epidermal growth factor receptor ligands in response to tumor necrosis factor α and interferon γ. These cytokines also promote de novo synthesis of numerous chemokines, including CCL2/MCP-1, CCL5/RANTES, CXCL10/IP-10, and CXCL8/IL-8, in turn responsible for the recruitment of different leukocyte populations. This study demonstrates that stimulation of EGFR down-regulates CCL2, CCL5, and CXCL10, while it increases CXCL8 expression in keratinocytes. Conversely, EGFR signaling blockade produces opposite effects, with increased CCL2, CCL5, and CXCL10, and reduced CXCL8 expression. In a mouse model of contact hypersensitivity, a single topical administration of a selective EGFR kinase blocker before antigen challenge results in a markedly enhanced immune response with increased chemokine expression and heavier inflammatory cell infiltrate. Targeting EGFR on epithelial cells may thus have profound impact on inflammatory and immune responses.

Original languageEnglish
Pages (from-to)303-312
Number of pages10
JournalAmerican Journal of Pathology
Issue number1
Publication statusPublished - Jul 1 2003


ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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