Staphylococcus epidermidis augments human β-defensin-3 synthesis through the transforming growth factor alpha-epidermal growth factor receptor cascade

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Abstract

Background

Epidermal growth factor receptor inhibitors (EGFRIs) reduce β-defensin 3 (BD3) from keratinocytes stimulated by S. epidermidis, potentially leading to the development of acneiform rashes in patients undergoing EGFRIs treatment. However, the mechanism through which S. epidermidis induces BD3 via EGFR remains incompletely understood.

Objective

To elucidate the BD3 production pathway triggered by S. epidermidis.

Methods

To assess the impact of S. epidermidis on EGFR ligand expression, the levels of released EGFR ligands in the keratinocyte culture medium following S. epidermidis stimulation were quantified using ELISA. Subsequently, to confirm the synergistic effect of TGF-α and S. epidermidis, we administered S. epidermidis and TGF-α to the keratinocyte culture medium and measured the expression levels of BD3. In addition, we stimulated Toll-like receptor 2 (TLR2)-knockdown keratinocytes with S. epidermidis and measured the expression levels of TGF-α.

Results

While S. epidermidis did not induce EGF and HB-EGF, they increased TGF-α. The expression of BD3 was higher in keratinocytes stimulated by S. epidermidis in the presence of TGF-α, as compared to its absence. Moreover, both S. epidermidis- and TGF-α-induced BD3 were significantly suppressed by cetuximab. The expression levels of TGF-α induced by S. epidermidis were reduced in TLR2-knockdown keratinocytes

Conclusion

Our findings suggest that S. epidermidis induces the expression of TGF-α in keratinocytes through TLR2, which, in cooperation with TGF-α, stimulates the production of BD3.
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表皮葡萄球菌通过转化生长因子α-表皮生长因子受体级联促进人类β-防御素-3的合成
背景:表皮生长因子受体抑制剂(EGFRIs)可减少表皮葡萄球菌刺激角质形成细胞产生的β-防御素3(BD3),从而可能导致接受EGFRIs治疗的患者出现痤疮样皮疹。然而,表皮葡萄球菌通过表皮生长因子受体诱导 BD3 的机制仍不完全清楚:阐明表皮葡萄球菌诱导 BD3 的产生途径:为了评估表皮葡萄球菌对表皮生长因子受体配体表达的影响,使用 ELISA 定量表皮葡萄球菌刺激后角质形成细胞培养液中释放的表皮生长因子受体配体的水平。随后,为了证实 TGF-α 和表皮葡萄球菌的协同作用,我们在角质形成细胞培养液中加入了表皮葡萄球菌和 TGF-α,并测定了 BD3 的表达水平。此外,我们还用表皮葡萄球菌刺激了Toll样受体2(TLR2)敲除的角质形成细胞,并测量了TGF-α的表达水平:结果:表皮葡萄球菌没有诱导 EGF 和 HB-EGF,但增加了 TGF-α。在有 TGF-α 的情况下,表皮葡萄球菌刺激的角质形成细胞中 BD3 的表达量比没有 TGF-α 时要高。此外,西妥昔单抗还能显著抑制表皮葡萄球菌和 TGF-α 诱导的 BD3。表皮葡萄球菌诱导的 TGF-α 的表达水平在 TLR2-敲除的角质形成细胞中有所降低 结论:我们的研究结果表明,表皮葡萄球菌通过 TLR2 诱导角质形成细胞中 TGF-α 的表达,TLR2 与 TGF-α 合作刺激 BD3 的产生。
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CiteScore
7.60
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