Increased cellular proliferation and inflammatory cytokines in tonsils derived from children with obstructive sleep apnea.

Increased cellular proliferation and inflammatory cytokines in tonsils derived from children with obstructive sleep apnea.
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DOI:
10.1203/pdr.0b013e3181b453e3
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发表时间:
2009-10
期刊:
影响因子:
3.6
通讯作者:
Gozal D
Gozal D
中科院分区:
医学3区
文献类型:
--
作者:
Kim J;Bhattacharjee R;Dayyat E;Snow AB;Kheirandish-Gozal L;Goldman JL;Li RC;Serpero LD;Clair HB;Gozal D

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扁桃体肥大是儿童阻塞性睡眠呼吸暂停(OSA)和复发性扁桃体炎(RI)的主要病理生理机制。阻塞性睡眠呼吸暂停综合征患者扁桃体炎症反应的各种介质表达增加,提示我们假设阻塞性睡眠呼吸暂停儿童局部和全身炎症反应增强将促进扁桃体增殖。对OSA和RI患儿行腺扁桃体切除术后回收的扁桃体进行混合细胞培养,并对增殖率进行评估。同时对细胞进行培养,以测定促炎症细胞因子水平、抗氧化蛋白水平和mRNA表达水平。OSA扁桃体的细胞增殖率显著高于RI(P<0.01),其中CD3+、CD4+和CD8+细胞的增殖率在OSA高于RI(P<0.05)。此外,促炎细胞因子如肿瘤坏死因子-α、白介素6和白介素1α在阻塞性睡眠呼吸暂停综合征患者的扁桃体中高表达。此外,抗氧化蛋白硫氧还蛋白(Trx)在OSA扁桃体的mRNA和蛋白水平也有高表达(p<0.01)。因此,与RI儿童相比,OSA儿童扁桃体中的T细胞处于高度增殖状态,并与促炎细胞因子和TRX的产生增加有关。
Adenotonsillar hypertrophy is the major pathophysiological mechanism underlying obstructive sleep apnea (OSA) and recurrent tonsillitis (RI) in children. The increased expression of various mediators of the inflammatory response in tonsils of OSA patients prompted our hypothesis that the enhanced local and systemic inflammation in OSA children would promote tonsillar proliferation. Mixed cell cultures from tonsils recovered during adenotonsillectomy in children with OSA and RI were established, and proliferative rates were assessed. Cells were also cultured to determine levels of pro-inflammatory cytokines and anti-oxidant protein levels and mRNA expression. Global cell proliferative rates from OSA tonsils were significantly higher than RI (P<0.01), with CD3+, CD4+, and CD8+ cell proliferation being higher in OSA (P<0.05). Moreover, pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1α were highly expressed in OSA-derived tonsils. Furthermore, thioredoxin (TRX), an anti-oxidant protein, was also highly expressed in OSA tonsils at the mRNA and protein levels (p<0.01). Thus, T-cells are in a highly proliferative state in the tonsils of children with OSA, and are associated with increased production of proinflammatory cytokines and TRX, when compared to children with RI.