刺激性接觸性皮膚炎對毛囊週期的影響

Abstract

摘要 毛髮週期可以分為三個階段；生長期(anagen)，退化期(categen)，休止期(telogen)。這個生長與休眠再到掉落的周期性構成了毛髮的生長週期，此生長週期會不斷的循環直到生命結束。 促進生長期的提前或是延長生長期則是解決禿髮的方法，而目前已知在小鼠模型中，拔毛(plucking)和傷口的癒合的過程中(wounding)皆可以造成毛髮的再生。本實驗想了解是否有其他方法在小鼠的模型中也能夠造成相同或相似的毛髮再生的情形。因此，本實驗利用十二烷基硫酸(sodium dodecyl sulfate, SDS)建立刺激性接觸性皮膚炎模式並觀察其對於毛囊的影響。 實驗結果顯示7.5% SDS刺激後發現毛囊形態會隨著時間改變，毛囊並提前進入生長期。而且利用免疫螢光染色發現確實會誘發毛囊幹細胞活化。 進一步探討SDS造成發炎而誘發毛囊再生機制，結果顯示在SDS處理後會逐漸刺激先天性免疫的反應，如巨噬細胞(macrophages)、嗜中性白血球(neutrophils)增多，同時也發現許多參與發炎的細胞激素其mRNA以及蛋白表現量均有顯著性增高如:TNF-α(tumor necrosis factor)、介白素-1(interleukin 1) IL-1α、IL-1β、IL-1Ra 、IL-1 Receptor1與VEGF(vascular endothelial growth factor)等。 最後利用不同抑制劑或是基因剃除老鼠確認接觸性皮膚炎誘發毛囊再生的關鍵因子，實驗結果發現TNF-α inhibitor、TNFR knockout mice、IL-1R1 knockout mice、Neutrophil depletion antibody均無法阻止SDS所誘發的發炎導致毛囊再生。因此SDS所誘發的發炎反應中可能有其他的機制參與。 關鍵字: 十二烷基硫酸、接觸性刺激性皮膚炎、毛囊再生、免疫反應、毛囊幹細胞

Abstract The hair cycle consists of three phages, including growth (anagen), involution (catagen), and quiescence (telogen). Hair follicles undergo repetitive growth cycles throughout life. Promoting transition from telogen to anagen early and preventing transition from anagen to catagen are the possible treatment for alopecia. Previous researches showed that hair plucking and wounding could induce hair follicle regeneration . The present study is aimed at seeking for other methods to induce hair regeneration. We used sodium dodecyl sulfate (SDS) to establish irritant contact dermatitis model and found that 7.5% SDS can fasten anagen entry. We demonstrated SDS could induce hair follicle stem cells and secondary hair germ activation. Next, we explore the molecular mechanisms of hair follicle regeneration induced by contact dermatitis.The results show that SDS can stimulate innate immune responses and induce macrophage and neutrophil infiltration. mRNA and protein expression of inflammation-associated cytokines were upregulated significantly, such as TNF-α(tumor necrosis factor)、 IL-1(interleukin 1) family, including IL-1α、IL-1β、IL-1Ra 、IL-1 receptor1, and VEGF(vascular endothelial growth factor). Finally, we use different inhibitors or gene knockout mice to clarify the key factors in contact dermatitis induced hair follicle regeneration. The results show that TNF-α inhibitor, TNFR knockout mice, IL-1R1 knockout mice and neutrophil depletion were unable to block SDS induced hair follicle regeneration. The result indicates that other important mechanisms may be involved in promoting anagen entry. key words: sodium dodecyl sulfate (SDS)、irritant contact dermatitis、hair follicle regeneration、inflammation response、hair follicle stem cells