Period2 gene regulates diurnal changes of nasal symptoms in an allergic rhinitis mouse model

Autor:	Z Q Han, Ze-Qing Li, Chang-Qing Zhao, Chao Li, Ping-Chang Yang, Yun-Fang An, Fengli Cheng
Rok vydání:	2020
Předmět:	medicine.medical_specialty endogenous glucocorticoid Period (gene) Circadian clock Mucous membrane of nose immune response Mice 03 medical and health sciences Th2 Cells 0302 clinical medicine RAR-related orphan receptor gamma Internal medicine circadian clock medicine Animals Immunology and Allergy Circadian rhythm 030223 otorhinolaryngology mouse allergic rhinitis business.industry GATA3 Interleukin Per2 Period Circadian Proteins Original Articles Rhinitis Allergic Eosinophils PER2 Disease Models Animal Nasal Mucosa Endocrinology 030228 respiratory system Otorhinolaryngology Cytokines Th17 Cells Original Article business
Zdroj:	International Forum of Allergy & Rhinology
ISSN:	2042-6984 2042-6976
DOI:	10.1002/alr.22607
Popis:	Background 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. Methods 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. Results 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 Gata3 and Rorγt expression levels that were enhanced at ZT4 and reduced at ZT16 in the AR group. Conclusion 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.
Databáze:	OpenAIRE
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