Treatment of Cultured Sebocytes with an EGFR Inhibitor Does Not Lead to Significant Upregulation of Inflammatory Biomarkers

ABSTRACT

BACKGROUND: Epidermal growth factor receptor (EGFR) inhibitors are being used to treat malignancies originating from epithelia. Unfortunately, blocking the EGFR pathway leads to various side effects, most frequently acneiform eruptions. OBJECTIVE: To probe the mechanism underlying this side effect, we investigated the effect of EGFR inhibitors on cultured sebocytes. METHODS: To examine the effects of an EGFR inhibitor (cetuximab, Erbitux(R) 10 ng/ml) and the effects of EGFR ligands, such as epidermal growth factor (EGF, 10 ng/ml) and transforming growth factor-alpha (TGF-alpha, 5 ng/ml), on the production of inflammatory cytokines in cultured sebocytes, we used reverse transcriptase-polymerase chain reaction, immunocytofluorescence and Western blots. Outcomes included the expression of interleukin (IL)-1, IL-6, tumor necrosis factor-alpha (TNF-alpha), peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and EGFR. RESULTS: There were no significant differences in the expression of IL-1, IL-6, TNF-alpha, PPAR-gamma and EGFR between (a) groups treated with an EGFR inhibitor or an EGFR ligand and (b) the control group, except for a significant increase in the expression of IL-1 in the EGF-treated group. CONCLUSION: EGFR inhibitors and EGFR ligands do not provoke the expression of inflammatory biomarkers in cultured sebocytes. The role of the sebaceous glands in EGFR inhibitor-induced acneiform eruption should be investigated more thoroughly.