Interleukin-1 beta-induced inhibition of hair growth in vitro is mediated by cyclic AMP
Interleukin-1 beta-induced inhibition of hair growth in vitro is mediated by cyclic AMP
复制标题
DOI：
10.1111/1523-1747.ep12285625
复制
发表时间：
1997-01-01
影响因子：
6.5
通讯作者：
Happle, R
中科院分区：
文献类型：
--
作者：
Hoffmann, R;Eicheler, W;Happle, R
白细胞介素(IL)-1在体外已被证明是一种有效的毛发生长抑制剂，我们推测该细胞因子可能是斑秃淋巴细胞攻击过程中导致脱发的决定性因素，但目前对于IL-1β介导的毛发生长抑制所涉及的细胞内途径和毛囊内的信号转导过程都不清楚，因此我们研究了细胞内的细胞内信号转导过程。 参与人类毛发体外生长的信号。通过显微解剖从头皮活检中分离毛囊，并通过图像分析每天测量头发生长。我们单独使用特定抑制剂或激活剂或与 IL-1 β 组合评估细胞内信号转导元件。钙离子载体 A 23187 诱导毛发生长快速且完全停止，佛波醇 12-肉豆蔻酸 13-乙酸酯 (PMA)、金雀异黄素或 IL-1 β 使毛发生长减少约 60%-80%。 IL-1β 引起的毛发生长停滞不会被蛋白激酶 C 的特异性抑制剂钙磷蛋白 C 拮抗，相反，IL-1β 与百日咳毒素或 H 1004 共孵育中和了 IL-1β 的作用，而二丁酰-cAMP 和霍乱毒素（一种腺苷酸环化酶激活剂）抑制毛发生长。这些数据表明，cAMP 充当 IL-1β 诱导的毛发生长抑制的第二信使。此外，我们的数据表明，体外毛发生长取决于细胞内 Ca2+ 水平以及酪氨酸激酶和蛋白激酶 C 的激活。我们无法检测到负责增强体外毛发生长的信号转导元件。
Interleukin (IL)-1 has been shown to be a potent inhibitor of hair growth in vitro, We hypothesized that this cytokine might be a decisive factor causing hair loss during the lymphocytic attack in alopecia areata, Neither the intracellular pathways involved in hair growth inhibition mediated by IL-1 beta nor the signal transduction processes within hair follicles in general are known, We therefore investigated the intracellular signals involved in human hair growth in vitro. Hair follicles were isolated from scalp biopsies by microdissection, and hair growth was measured daily by image analysis. We assessed intracellular signal transducing elements using specific inhibitors or activators either alone or in combination with IL-1 beta. The calcium ionophore A 23187 induced a rapid and complete arrest of hair growth, and phorbol-12-myristate-13-acetate (PMA), genistein, or IL-1 beta decreased hair growth by approximately 60%-80%. IL-1 beta-elicited hair growth arrest was not antagonized by calphostin C, a specific inhibitor of protein kinase C, In contrast, coincubation of IL-1 beta with pertussis toxin or H 1004 neutralized the effect of IL-1 beta, and dibutyryl-cAMP and cholera toxin, an activator of adenylate cyclase, inhibited hair growth, These data suggest that cAMP acts as a second messenger for IL-1 beta-induced inhibition of hair growth. Moreover, our data indicate that in vitro hair growth is dependent on intracellular Ca2+ levels and activation of tyrosine kinase as well as protein kinase C. We were unable to detect a signal transducing element responsible for enhanced hair growth in vitro.