Differential expression of adhesion molecules by sinonasal fibroblasts among control and chronic rhinosinusitis patients
Differential expression of adhesion molecules by sinonasal fibroblasts among control and chronic rhinosinusitis patients
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DOI：
10.2500/ajra.2013.27.3934
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发表时间：
2013-09-01
影响因子：
2.6
通讯作者：
Mulligan, Jennifer K.
中科院分区：
文献类型：
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作者：
Oyer, Samuel L.;Nagel, Whitney;Mulligan, Jennifer K.
背景资料：慢性鼻窦炎（CRS）的特征是炎症细胞迁移到鼻窦组织中，并在细胞因子的环境下引起炎症。成纤维细胞可通过表达白细胞粘附分子如血管细胞粘附分子（VCAM）和细胞间粘附分子（ICAM）来促进炎症。VCAM吸引嗜酸性粒细胞和肥大细胞，导致Th 2偏斜，ICAM吸引嗜中性粒细胞，并在较小程度上吸引嗜酸性粒细胞，并导致混合Th 1/Th 2偏斜。本研究的目的是比较窦成纤维细胞粘附分子表达离体CRS亚型和体外细胞因子stimulation.Methods：窦活检标本取自对照组（n = 13），CRS无鼻息肉（CRSsNP，n = 6），CRS鼻息肉（CRSwNP，n = 15）。通过流式细胞术从组织活检标本的单细胞悬浮液测量VCAM和ICAM的离体水平。VCAM和ICAM表达的细胞因子暴露的变化进行了评估，在体外培养的鼻窦成纤维细胞与肿瘤坏死因子（TNF）-α，白细胞介素（IL）-4，IFN-γ的治疗结果：离体VCAM的表达是最低的控制，较高的CRSsNP，最高的CRSwNP。在体外用TNF-α和IL-4刺激，而不是IFN-γ刺激，增加CRSsNP中的VCAM，而CRSwNP中的表达在除IFN-γ外的所有治疗中保持升高。两种CRS亚型的离体ICAM表达均升高。在体外刺激与TNF-α和IFN-γ，但不是IL-4，增加ICAM的表达在所有患者中的CRSsNP subgroup.Conclusion之间的最大影响：鼻窦炎中的鼻窦成纤维细胞粘附分子的表达因疾病状态而异，并选择性地受到炎症细胞因子的影响。
Background: Chronic rhinosinusitis (CRS) is characterized by inflammatory cell migration into sinus tissue with resultant inflammation fueled by a milieu of cytokines. Fibroblasts may contribute to inflammation through expression of leukocyte adhesion molecules such as vascular cell adhesion molecule (VCAM) and intercellular adhesion molecule (ICAM). VCAM attracts eosinophils and mast cells contributing to Th2 skewing, and ICAM attracts neutrophils and to a lesser degree, eosinophils, and contributes to mixed Th1/Th2 skewing. The purpose of this study was to compare sinus fibroblast adhesion molecule expression ex vivo among CRS subtypes and in vitro after cytokine stimulation.Methods: Sinus biopsy specimens were taken from control patients (n = 13), CRS without nasal polyposis (CRSsNP, n = 6), and CRS with nasal polyposis (CRSwNP, n = 15). Ex vivo levels of VCAM and ICAM were measured by flow cytometry from single cell suspensions of tissue biopsy specimens. Changes in VCAM and ICAM expression to cytokine exposure were assessed using in vitro cultured sinonasal fibroblasts treated with tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, or interferon (IFN)-gamma.Results: Ex vivo VCAM expression was lowest in controls, higher in CRSsNP, and highest in CRSwNP. In vitro stimulation with TNF-alpha and IL-4, but not IFN-gamma, increased VCAM among CRSsNP, while expression in CRSwNP remained elevated with all treatments except IFN-gamma. Ex vivo ICAM expression was elevated in both CRS subtypes. In vitro stimulation with TNF-alpha and IFN-gamma, but not IL-4, increased ICAM expression in all patients with the largest effects among the CRSsNP subgroup.Conclusion: Sinonasal fibroblast expression of adhesion molecules in sinusitis varies by disease state and is selectively influenced by exposure to inflammatory cytokines.