Effects of interleukin-18 on cardiac fibroblast function and gene expression.
Effects of interleukin-18 on cardiac fibroblast function and gene expression.
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白介素18对心脏成纤维细胞功能和基因表达的影响。
DOI：
10.1016/j.cyto.2010.10.002
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发表时间：
2011-01
期刊：
影响因子：
3.8
通讯作者：
Carver, Wayne
中科院分区：
文献类型：
--
作者：
Fix, Charity;Bingham, Kellie;Carver, Wayne
成纤维细胞是负责心脏细胞外基质合成和重塑的主要细胞类型。已经确定了许多因素，包括生长因子、激素和机械力，可以调节心脏成纤维细胞产生细胞外基质。包括促炎细胞因子和趋化因子在内的炎症介质也会影响心脏纤维化。最近的研究表明，IL-18 可促进心脏成纤维细胞的促纤维化反应；然而，这种细胞因子对成纤维细胞功能其他方面的影响尚未得到研究。虽然成纤维细胞长期以来因其在细胞外基质的产生和重塑中的作用而闻名，但这些细胞的其他功能现在才开始被人们所认识。我们假设暴露于白细胞介素 18 会刺激成纤维细胞行为的其他方面，这些行为对心肌重塑很重要，包括增殖、迁移和胶原蛋白重组。从成年雄性大鼠心脏中分离出成纤维细胞，并进行生物测定以确定白细胞介素 18 对成纤维细胞功能的影响。用白细胞介素 18 (1-100 ng/ml) 处理成纤维细胞会导致细胞外基质成分的产生增加，以及这些细胞对三维胶原蛋白支架的重塑或收缩。此外，暴露于白细胞介素18会刺激成纤维细胞迁移和增殖。用 IL-18 处理心脏成纤维细胞导致 c-Jun N 末端激酶 (JNK) 和磷酸肌醇 3-激酶 (PI3-激酶) 途径快速激活。药物抑制剂的研究表明，这些途径的激活对于白细胞介素 18 介导的成纤维细胞功能改变至关重要。这些研究表明，IL-18 在调节心脏成纤维细胞功能中发挥作用，并且可能是病理性心肌重塑过程中炎症-纤维化级联的重要组成部分。
Fibroblasts are the primary cell type responsible for synthesis and remodeling of the extracellular matrix in the heart. A number of factors including growth factors, hormones and mechanical forces have been identified that modulate the production of extracellular matrix by cardiac fibroblasts. Inflammatory mediators including proinflammatory cytokines and chemokines also impact fibrosis of the heart. Recent studies have illustrated that interleukin-18 promotes a pro-fibrotic response in cardiac fibroblasts; however the effects of this cytokine on other aspects of fibroblast function have not been examined. While fibroblasts have long been known for their role in production and remodeling of the extracellular matrix, other functions of these cells are only now beginning to be appreciated. We hypothesize that exposure to interleukin-18 will stimulate other aspects of fibroblast behavior important in myocardial remodeling including proliferation, migration and collagen reorganization. Fibroblasts were isolated from adult male rat hearts and bioassays performed to determine the effects of interleukin-18 on fibroblast function. Treatment of fibroblasts with interleukin-18 (1–100 ng/ml) resulted in increased production of extracellular matrix components and remodeling or contraction of three-dimensional collagen scaffolds by these cells. Furthermore, exposure to interleukin-18 stimulated fibroblast migration and proliferation. Treatment of heart fibroblasts with interleukin-18 resulted in the rapid activation of the c-Jun N-terminal kinase (JNK) and Phosphoinositide 3-kinase (PI3-kinase) pathways. Studies with pharmacological inhibitors illustrated that activation of these pathways is critical to interleukin-18 mediated alterations in fibroblast function. These studies illustrate that interleukin-18 plays a role in modulation of cardiac fibroblast function and may be an important component of the inflammation- fibrosis cascade during pathological myocardial remodeling.
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DOI：
10.1152/ajpheart.00928.2007
发表时间：
2007-12-01
影响因子：
4.8
作者：
Cortez, Dolores M.;Feldman, Marc D.;Chandrasekar, Bysani
通讯作者：
Chandrasekar, Bysani
影响因子：
3.7
作者：
GULLBERG, D;TINGSTROM, A;RUBIN, K
通讯作者：
RUBIN, K
影响因子：
5.4
作者：
Hart, Gili;Flaishon, Liat;Shachar, Idit
通讯作者：
Shachar, Idit
影响因子：
20.1
作者：
BURGESS, ML;CARVER, WE;BORG, TK
通讯作者：
BORG, TK
影响因子：
5.5
作者：
Antonopoulos, Christos;Cumberbatch, Marie;Groves, Richard W.
通讯作者：
Groves, Richard W.