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 Ⓡ 10 ng/ml) and the effects of EGFR ligands, such as epidermal growth factor (EGF, 10 ng/ml) and transforming growth factor-α (TGF-α, 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-α (TNF-α), peroxisome proliferator-activated receptor-γ (PPAR-γ) and EGFR. Results: There were no significant differences in the expression of IL-1, IL-6, TNF-α, PPAR-γ 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. (Ann Dermatol 23(1) 12∼18, 2011)

Recent advances in the endocrinology of the sebaceous gland

“… 69 Interestingly, a more recent paper has shown that cetuximab does not induce inflammatory mediator release from in vitro cultured sebocytes, while it does increase their lipogenesis. 70,71 This hints at the possibility that a more complex signaling network is responsible for the aforementioned lesions. Besides EGF, the role of fibroblast growth factor receptor-2b (FGFR2b) coupled signaling in the control of sebaceous functions and the development of acne has also been proposed.…”

The investigation of the amounts and expressions of epidermal growth factor, epidermal growth factor receptor, and epidermal growth factor receptor gene polymorphisms in acne vulgaris

“…On the other hand, there are some evidence supporting EGFs priming role in AV. EGF is known to increase IL‐1 secretion 10,13 which initiates follicular hyperkeratosis and comedogenesis 8 . In this way, EGF may have a role in AV pathogenesis from the very first step 1,14,15 .…”

Epidermal growth factor receptor and the sebaceous gland

“…On the other hand, EGF stimulated proliferation of and suppressed lipogenesis in hamster sebocytes . Interestingly, EGFR inhibition treatment affects the hair follicle but does not seem to induce primary changes in the sebaceous gland .…”

“…Despite these facts and although EGFR has been shown to play important roles during the development, homeostasis and pathology of the hair follicle and the interfollicular epidermis , there are few and contradictory data on the role of EGF/EGFR in sebaceous glands, probably due to the rarity of sebaceous tumors. EGF was shown not to affect human sebocyte proliferation in vitro but induced interleukin (IL)‐1 secretion . This finding has been associated with initiation of comedogenesis and follicular hyperkeratosis in vivo and ex vivo , indicating an increased sebaceous differentiation in vitro .…”