Period2 gene regulates diurnal changes of nasal symptoms in an allergic rhinitis mouse model.
Period2 gene regulates diurnal changes of nasal symptoms in an allergic rhinitis mouse model.
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period2基因调节过敏性鼻炎小鼠模型鼻部症状的昼夜变化
DOI：
10.1002/alr.22607
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发表时间：
2020-11
影响因子：
6.4
通讯作者：
Zhao CQ
中科院分区：
文献类型：
--
作者：
Cheng FL;An YF;Han ZQ;Li C;Li ZQ;Yang PC;Zhao CQ
过敏性鼻炎（AR）症状表现出与生物钟相关的显著24小时变化。虽然内源性糖皮质激素同步昼夜节律振荡器在鼻粘膜，AR的确切机制仍不清楚。因此，使用小鼠模型，我们研究了生物钟基因与不同时间点AR症状之间的关联。基于皮质酮水平的节律性分泌，我们选择了两个时间点，ZT 4（10：00 AM）和ZT 16（10：00 PM），观察鼻部症状、免疫反应和昼夜节律基因周期（Per）表达的动态变化。在AR组中，ZT 4时的鼻症状评分显着高于ZT 16，ZT 4时嗜酸性粒细胞、肥大细胞和总免疫球蛋白E水平增加幅度更大。得分与皮质酮水平的波动呈负相关。AR组中，与ZT 16相比，ZT 4时辅助性T细胞1（Th 1）细胞计数和干扰素γ水平显着下降，而Th 2细胞; Th 17细胞;与ZT 16相比，ZT 4时白细胞介素（IL）-4、-13和-17A水平显着增加。此外，AR组Per 2基因表达水平在ZT 4时减弱，在ZT 16时升高，但与Th 2和Th 17反应呈负相关，Th 2和Th 17反应与AR组Gata 3和Rorγt表达水平在ZT 4时增强，在ZT 16时降低。我们的结果表明，Per 2基因可能会影响AR症状严重程度的昼夜变化，部分原因是其对免疫细胞中GATA 3和RORγt水平的昼夜节律调节可能具有抗炎作用。这进一步证明了AR昼夜节律的神经免疫内分泌机制，并为AR的时序方法提供了新的见解。
Allergic rhinitis (AR) symptoms exhibit prominent 24‐hour variations associated with the biological clock. Although endogenous glucocorticoids synchronize circadian oscillator in the nasal mucosa, the precise mechanism of AR remains unclear. Therefore, using a mouse model, we investigated the association between circadian‐clock genes and AR symptoms at various time‐points. Based on the rhythmic secretion of corticosterone levels, we chose 2 time‐points, ZT4 (10:00 AM) and ZT16 (10:00 PM), to observe dynamic changes of nasal symptoms, immunologic responses, and circadian‐clock gene period (Per) expressions. In the AR group, nasal symptom scores at ZT4 were significantly higher than at ZT16, with a greater increase in eosinophils, mast cells, and total immunoglobulin E levels at ZT4. The scores had a negative correlation with fluctuation of corticosterone levels. T‐helper 1 (Th1) cell counts and interferon‐γ levels decreased significantly at ZT4 compared with ZT16 in the AR group, whereas Th2 cells; Th17 cells; and interleukin (IL)‐4, ‐13, and ‐17A levels increased significantly at ZT4 compared with ZT16. Furthermore, Per2 gene expression levels were attenuated at ZT4 and elevated at ZT16, but correlated negatively with Th2 and Th17 responses associated with G ata3 and Rorγt expression levels that were enhanced at ZT4 and reduced at ZT16 in the AR group. Our results suggest that the Per2 gene may influence diurnal variations of AR symptom severity, partially through its possible anti‐inflammatory effect on the circadian regulation of GATA3 and RORγt levels in immune cells. This further demonstrates the neural‐immune‐endocrinal mechanism of circadian rhythm in AR and sheds new light on chronotherapeutic approaches to AR.
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影响因子：
12.4
作者：
Ando N;Nakamura Y;Ishimaru K;Ogawa H;Okumura K;Shimada S;Nakao A
通讯作者：
Nakao A
影响因子：
4.6
作者：
Nakamura Y;Ishimaru K;Shibata S;Nakao A
通讯作者：
Nakao A
小鼠巨噬细胞，树突细胞和B细胞中时钟基因的昼夜节律表达。
影响因子：
15.1
作者：
Silver, Adam C.;Arjona, Alvaro;Hughes, Michael E.;Nitabach, Michael N.;Fikrig, Erol
通讯作者：
Fikrig, Erol
影响因子：
4.6
作者：
Tanabe K;Kitagawa E;Wada M;Haraguchi A;Orihara K;Tahara Y;Nakao A;Shibata S
通讯作者：
Shibata S
DOI：
10.1073/pnas.0909733106
发表时间：
2009-10-13
影响因子：
11.1
作者：
So, Alex Y. -L.;Bernal, Teresita U.;Feldman, Brian J.
通讯作者：
Feldman, Brian J.