Differential expression of thymus- and activation-regulated chemokine (CCL17) and macrophage-derived chemokine (CCL22) by human fibroblasts from cornea, skin, and lung

Differential expression of thymus- and activation-regulated chemokine (CCL17) and macrophage-derived chemokine (CCL22) by human fibroblasts from cornea, skin, and lung
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DOI:
10.1067/mai.2003.59
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发表时间:
2003-03-01
影响因子:
14.2
通讯作者:
Nishida, T
Nishida, T
中科院分区:
医学1区
文献类型:
--
作者:
Fukuda, K;Fujitsu, Y;Nishida, T

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背景:眼表、皮肤和肺部的过敏性疾病由 T(H)2 细胞引发,T(H)2 细胞由胸腺和活化调节趋化因子(TARC;CCL17)和巨噬细胞衍生趋化因子(MDC;CCL22)招募。常驻成纤维细胞被认为通过趋化因子的产生促进炎症细胞浸润。 目的:我们试图深入了解眼、皮肤和肺这些过敏性疾病之间明显的临床差异,并比较角膜、真皮和肺成纤维细胞产生 TARC 和 MDC 的能力。 方法:通过 ELISA 测定释放到培养物上清液中的趋化因子的量,并计算细胞内趋化因子 mRNA 的丰度。通过逆转录和实时 PCR 分析进行定量。结果:单独使用 TNF-α、IFN-γ、IL-4 或 IL-13 均不会诱导角膜、真皮或肺成纤维细胞中 TARC 的释放,也不影响 TARC mRNA 的量。然而,TNF-α与IL-4或IL-13的组合显着增加了角膜和真皮成纤维细胞中的TARC释放和TARC mRNA的丰度,但在肺成纤维细胞中则没有。在用任何细胞因子刺激的 3 种成纤维细胞中均未检测到 MDC 释放或 MDC mRNA。 结论:这些结果表明细胞因子对 TARC 表达的调节在角膜、皮肤或肺来源的成纤维细胞之间存在差异。因此,角膜和真皮成纤维细胞可能是过敏性炎症期间 TARC 的重要来源。 (J Allergy Clin Immunol 2003;111:520-6.)。
Background: Allergic diseases of the ocular surface, skin, and lung are triggered by T(H)2 cells, which are recruited by thymus- and activation-regulated chemokine (TARC; CCL17) and macrophage-derived chemokine (MDC; CCL22). Resident fibroblasts are thought to contribute to inflammatory cell infiltration through chemokine production.Objective: We sought to provide insight into the clinical differences apparent among these allergic diseases of the eye, skin, and lung, and we compared the abilities of corneal, dermal, and lung fibroblasts to produce TARC and MDC.Methods: The amounts of chemokines released into the culture supernatant were determined by means of ELISA, and the intracellular abundance of chemokine mRNAs was quantitated by means of reverse transcription and real-time PCR analysis.Results: Neither TNF-alpha, IFN-gamma, IL-4, nor IL-13 alone induced the release of TARC from or affected the amount of TARC mRNA in corneal, dermal, or lung fibroblasts. The combination of TNF-a with either IL-4 or IL-13, however, markedly increased both TARC release and the abundance of TARC mRNA in corneal and dermal fibroblasts, but not in lung fibroblasts. Neither MDC release nor MDC mRNA was detected in any of the 3 types of fibroblasts stimulated with any of the cytokines examined.Conclusion: These results indicate that cytokine regulation of TARC expression differs among fibroblasts derived from the cornea, skin, or lung. Corneal and dermal fibroblasts might thus be important sources of TARC during allergic inflammation. (J Allergy Clin Immunol 2003; 111:520-6.).