Melatonin regulates circadian clock proteins expression in allergic airway inflammation
Si-Nuo Guo,
Xu-Qin Jiang,
Ning Chen,
Si-Ming Song,
Yu Fang,
Qiu-Meng Xie,
Guang-He Fei,
Hui-Mei Wu
Affiliations
Si-Nuo Guo
Anhui Geriatric Institute, Department of Geriatric Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China; Key Laboratory of Respiratory Disease research and Medical Transformation of Anhui Province, Hefei, 230022, China
Xu-Qin Jiang
Key Laboratory of Respiratory Disease research and Medical Transformation of Anhui Province, Hefei, 230022, China; Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China
Ning Chen
Anhui Geriatric Institute, Department of Geriatric Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China; Key Laboratory of Respiratory Disease research and Medical Transformation of Anhui Province, Hefei, 230022, China
Si-Ming Song
Anhui Geriatric Institute, Department of Geriatric Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China; Key Laboratory of Respiratory Disease research and Medical Transformation of Anhui Province, Hefei, 230022, China
Yu Fang
Anhui Geriatric Institute, Department of Geriatric Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China; Key Laboratory of Respiratory Disease research and Medical Transformation of Anhui Province, Hefei, 230022, China
Qiu-Meng Xie
Key Laboratory of Respiratory Disease research and Medical Transformation of Anhui Province, Hefei, 230022, China; Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China
Guang-He Fei
Key Laboratory of Respiratory Disease research and Medical Transformation of Anhui Province, Hefei, 230022, China; Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China; Corresponding author. Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China
Hui-Mei Wu
Anhui Geriatric Institute, Department of Geriatric Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China; Key Laboratory of Respiratory Disease research and Medical Transformation of Anhui Province, Hefei, 230022, China; Corresponding author. Anhui Geriatric Institute, Department of Geriatric Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
Asthma demonstrates a strong circadian rhythm with disrupted molecular clock. Melatonin which can directly regulate circadian rhythm has been reported to alleviate asthma, but whether this effect is related to its regulation on circadian clock has not yet been known. Here, female C57BL/6 mice were challenged with ovalbumin (OVA) to establish allergic airway inflammation, and were treated with melatonin or Luzindole to investigate whether the expressions of circadian clock proteins were changed in response to OVA and were affected by exogenous/endogenous melatonin. Airway inflammation, mucus secretion, protein expressions of circadian proteins (Bmal1, Per1, Clock, Timeless, Cry1 and Cry2), melatonin biosynthetase (ASMT, AANAT) and melatonin receptor (Mel-1A/B–R) were analyzed accordingly. The results showed that in the successfully established allergic airway inflammation model, inflammatory cells infiltration, expressions of circadian clock proteins in the lung tissues of OVA-challenged mice were all notably up-regulated as compared to that of the vehicle mice. Meanwhile, the protein expression of ASMT and the level of melatonin in the lung tissues were reduced in allergic mice, while the expression of melatonin receptor Mel-1A/B–R was markedly increased. After addition of exogenous melatonin, the OVA-induced airway inflammation was pronouncedly ameliorated, while simultaneously the OVA-induced expressions of Per1 and Clock were further increased. However, a melatonin receptor antagonist Luzindole further augmented the OVA-induced airway inflammation, accompanied with remarkably decreased expressions of Per1, Bmal1, Cry1 and Cry2 but notably increased expression of Timeless. Collectively, our results demonstrated that the expression of circadian clock proteins was increased in the lungs during allergic airway inflammation, and Per1 was a clock protein that can be regulated by both exogenous and endogenous melatonin, suggesting Per1 may be an important potential circadian clock target for melatonin as a negative regulatory factor against Th2-type airway inflammation.
