Ann Dermatol.  2011 Feb;23(1):12-18. 10.5021/ad.2011.23.1.12.

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

• Lee WJ
• Chi SG
• Park DJ
• Kim JY
• Kim HY
• Lee SJ
• Kim DW
• Kim MK
• Kim JC
• Lee MW

• KMID: 2171946
• DOI: http://doi.org/10.5021/ad.2011.23.1.12

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.

Keyword

Cultured sebocytes; EGFR inhibitor; Inflammatory biomarkers

MeSH Terms

Acneiform Eruptions
Biomarkers
Blotting, Western
Cytokines
Epidermal Growth Factor
Interleukin-1
Interleukin-6
Interleukins
Ligands
Peroxisomes
Receptor, Epidermal Growth Factor
Sebaceous Glands
Tumor Necrosis Factor-alpha
Up-Regulation
Cytokines
Epidermal Growth Factor
Interleukin-1
Interleukin-6
Interleukins
Ligands
Receptor, Epidermal Growth Factor
Tumor Necrosis Factor-alpha

Figure

• 

  Fig. 1 Reverse transcription-polymerase chain reaction analysis for inflammatory cytokines, PPAR-γ and EGFR. EGF: epidermal growth factor, EGFR: epidermal growth factor receptor, TGF: transforming growth factor, IL: interleukin, TNF: tumor necrosis factor, PPAR: peroxisome proliferator-activated receptor.

• 

  Fig. 2 Semiquantitative reverse transcription-polymerase chain analyses for proinflammatory cytokines, PPAR-γ and EGFR. All proinflammatory biomarkers, except for IL-1 in the EGF-treated group and IL-6 in the EGFR inhibitor-treated group, were decreased in all of the treated groups compared with the control group. There were no statistically significant differences in proinflammatory biomarkers between the treated groups and control group (p>0.05). Bars represent mean±standard deviation. EGF: epidermal growth factor, EGFR: epidermal growth factor receptor, TGF: transforming growth factor, IL: interleukin, TNF: tumor necrosis factor, PPAR: peroxisome proliferator-activated receptor.

• 

  Fig. 3 Semiquantitative immunocytofluorescence analyses for the proinflammatory cytokines PPAR-γ and EGFR. All proinflammatory biomarkers, except for IL-1 in the EGF-treated group and PPAR-γ and EGFR in the TGF-α-treated group, were decreased in all of the treated groups compared with the control group. Bars represent mean±standard deviation. EGF: epidermal growth factor, EGFR: epidermal growth factor receptor, TGF: transforming growth factor, IL: interleukin, TNF: tumor necrosis factor, PPAR: peroxisome proliferator-activated receptor.

• 

  Fig. 4 Western blot assays of IL-1 in control, EGF-treated, EGFR inhibitor-treated and TGF-α-treated groups. EGF: epidermal growth factor, EGFR: epidermal growth factor receptor, TGF: transforming growth factor, IL: interleukin.

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  Fig. 5 Semiquantitative Western blot analyses for IL-1. IL-1 was increased in the EGF-treated group and decreased in the other groups when compared with the control group. EGF: epidermal growth factor, EGFR: epidermal growth factor receptor, TGF: transforming growth factor, IL: interleukin.

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