Interleukin-13 modulates collagen homeostasis in human skin and keloid fibroblasts.
Interleukin-13 modulates collagen homeostasis in human skin and keloid fibroblasts.
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发表时间：
2000-03
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通讯作者：
Alfonso Oriente;Neal S. Fedarko;S. Pacocha;S. Huang;L. M. Lichtenstein;D. Essayan
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作者：
Alfonso Oriente;Neal S. Fedarko;S. Pacocha;S. Huang;L. M. Lichtenstein;D. Essayan
白细胞介素（IL）-13与以纤维化为特征的多种疾病的发病机制有关。我们描述了IL-13对正常（NF）和瘢痕疙瘩（KF）成纤维细胞胶原稳态的作用，并将这些作用与IL-4和转化生长因子（TGF）-β（1）的作用进行了比较。总胶原生成上调NF刺激后48小时的IL-13，在KF中，IL-13刺激了更快的胶原反应。由IL-13诱导的胶原蛋白生成的动力学和幅度与由相似浓度的IL-4和TGF-β诱导的胶原蛋白生成的动力学和幅度相当（1）。I型胶原蛋白的产生是NF和KF产生的总胶原蛋白的两倍;然而，IL-4诱导的I型胶原蛋白和KF产生的总胶原蛋白比IL-13或TGF-β诱导的更短暂（1）。通过用IL-13刺激24 h诱导KF中的前胶原1 α 1基因表达。此外，IL-13在这三种细胞因子中诱导前胶原3 α 1基因表达的能力是独特的。最后，IL-13抑制了IL-1 β诱导的基质金属蛋白酶（MMP）-1和MMP-3的产生，并增强了NF产生的金属蛋白酶组织抑制剂（TIMP）-1;尽管IL-4也观察到了类似的作用，但TGF-β（1）短暂地增强了MMP-1和MMP-3的产生，而不影响TIMP-1。在KF中，IL-13和IL-4抑制MMP-3，而TGF-β 1增强MMP-3; TIMP-1不受任何三种细胞因子的影响。这些数据表明IL-13对胶原稳态的促纤维化作用和IL-13对成纤维细胞亚型中胶原稳态的潜在差异调节。
Interleukin (IL)-13 has been implicated in the pathogenesis of various diseases characterized by fibrosis. We describe the effects of IL-13 on collagen homeostasis from normal (NF) and keloid (KF) fibroblasts and compare these effects with those of IL-4 and transforming growth factor (TGF)-beta(1). Total collagen generation was up-regulated in NF after 48 h of stimulation by IL-13; in KF, IL-13 stimulated a more rapid collagen response. The kinetics and magnitude of collagen generation induced by IL-13 were equivalent to those induced by similar concentrations of IL-4 and TGF-beta(1). Collagen type I production paralleled total collagen generation from both NF and KF; however, IL-4-induced collagen type I and total collagen production from KF was more transient than that induced by either IL-13 or TGF-beta(1). Procollagen 1alpha1 gene expression was induced in KF by stimulation with IL-13 for 24 h. Moreover, IL-13 was unique among these three cytokines in its ability to induce gene expression for procollagen 3alpha1. Finally, IL-13 inhibited IL-1beta-induced matrix metalloproteinase (MMP)-1 and MMP-3 production and enhanced tissue inhibitor of metalloproteinase (TIMP)-1 generation from NF; although similar effects were observed with IL-4, TGF-beta(1) transiently enhanced MMP-1 and MMP-3 generation without effecting TIMP-1. In KF, IL-13 and IL-4 inhibited MMP-3, whereas TGF-beta(1) enhanced MMP-3; TIMP-1 was unaffected by any of the three cytokines. These data demonstrate both the profibrotic effects of IL-13 on collagen homeostasis and the potential differential regulation of collagen homeostasis in fibroblast subtypes by IL-13.