Human orbital fibroblasts are activated through CD40 to induce proinflammatory cytokine production
Human orbital fibroblasts are activated through CD40 to induce proinflammatory cytokine production
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DOI：
10.1152/ajpcell.1998.274.3.c707
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发表时间：
1998-03-01
影响因子：
5.5
通讯作者：
Phipps, RP
中科院分区：
文献类型：
--
作者：
Sempowski, GD;Rozenblit, J;Phipps, RP
CD 40是在某些骨髓源性细胞上发现的重要信号传导和活化抗原。最近，CD 40也被证明是由非造血细胞，包括某些人成纤维细胞，但不是其他人表达。关于CD 40在成纤维细胞上的功能知之甚少。目前的研究调查的假设，CD 40的眼眶成纤维细胞表达，并代表这些成纤维细胞和CD 40配体表达细胞，如T淋巴细胞和肥大细胞之间的相互作用的途径。我们在这里报告，眼眶结缔组织成纤维细胞，从正常捐助者和严重的甲状腺相关眼病（TAO）患者，表达功能性CD 40。干扰素-γ（500 U/ml）处理72 h后，CD 40上调约10倍。这些成纤维细胞通过用CD 40配体（CD 40 L）触发CD 40而被激活。这通过核因子-κ B的核转位以及分别诱导促炎和化学引诱细胞因子白细胞介素-6和白细胞介素-8来证明。这些数据支持眼眶成纤维细胞和浸润性T淋巴细胞之间通过CD 40-CD 40 L途径的同源相互作用可能促进在TAO和其他眼眶炎性疾病中观察到的组织重塑的概念。CD 40-CD 40 L相互作用的破坏可能代表减少TAO的炎症组分的治疗干预，TAO仍然是一个令人烦恼的临床问题。
CD40 is an important signaling and activation antigen found on certain bone marrow-derived cells. Recently CD40 has also been shown to be expressed by nonhematopoietic cells, including certain human fibroblasts, but not others. Little is known about the function of CD40 on fibroblasts. The current study investigates the hypothesis that CD40 is expressed on orbital fibroblasts and represents a pathway for interaction between these fibroblasts and CD40 ligand-expressing cells, such as T lymphocytes and mast cells. We report here that orbital connective tissue fibroblasts, obtained from normal donors and from patients with severe thyroid-associated ophthalmopathy (TAO), express functional CD40. CD40 is upregulated similar to 10-fold by interferon-gamma (500 U/ml) treatment for 72 h. These fibroblasts become activated through triggering of CD40 with CD40 ligand (CD40L). This is evidenced by nuclear translocation of nuclear factor-kappa B and induction of the proinflammatory and chemoattractant cytokines interleukin-6 and interleukin-8, respectively. These data support the concept that cognate interactions between orbital fibroblasts and infiltrating T lymphocytes, via the CD40-CD40L pathway, may promote the tissue remodeling observed in TAO and other inflammatory diseases of the orbit. Disruption of the CD40-CD40L interaction may represent a therapeutic intervention to reduce the inflammatory components of TAO, which remains a vexing clinical problem.