한빛사논문
- 조회443
전북대학교 의과대학
June-Mo Kim PhD1,*, Yoo Na Im PhD1,*, Yun-Jo Chung PhD2, Jung-ho Youm MD, PhD3, Suhn Young Im PhD4,#, Myung Kwan Han PhD5,#, Hern Ku Lee MD, PhD1,#
1Department of Immunology and Institute for Medical Science, Jeonbuk National University Medical School, Jeonju, Republic of Korea
2Center for University-wide Research Facilities, Jeonbuk National University Medical School, Jeonju, Republic of Korea
3Department of Preventive Medicine, Jeonbuk National University Medical School, Jeonju, Republic of Korea
4Department of Biological Sciences, College of Natural Sciences, Chonnam National University, Gwangju, Republic of Korea
5Department of Microbiology and Institute for Medical Science, Jeonbuk National University Medical School, Jeonju, Republic of Korea
*These authors contributed equally to this work
#These authors shared senior authorship
Corresponding Autors
Abstract
Background
The administration of L-glutamine (Gln) suppresses allergic airway inflammation via the rapid upregulation of MAPK phosphatase (MKP)-1, which functions as a negative regulator of inflammation by deactivating p38 and JNK mitogen-activated protein kinases (MAPKs). However, the role of endogenous Gln remains to be elucidated. Therefore, we investigated the mechanism by which endogenous Gln regulates MKP-1 induction and allergic airway inflammation in an ovalbumin-based murine asthma model.
Methods
We depleted endogenous Gln levels using L-γ-glutamyl-p-nitroanilide (GPNA), an inhibitor of the Gln transporter ASCT2, and glutamine synthetase small interfering (si)RNA. Lentivirus expressing MKP-1 was injected to achieve overexpression of MKP-1. Asthmatic phenotypes were assessed using our previously developed ovalbumin-based murine model, which is suitable for examining sequential asthmatic events, including neutrophil infiltration. Gln levels were analyzed using a Gln assay kit.
Results
GPNA or glutamine synthetase siRNA successfully depleted endogenous Gln levels. Importantly, homeostatic MKP-1 induction did not occur at all, which resulted in prolonged p38 MAPK and cytosolic phospholipase A2 (cPLA2) phosphorylation in Gln-deficient mice. Gln deficiency augmented all examined asthmatic reactions, but it exhibited a strong bias toward increasing the neutrophil count, which was not observed in MKP-1-overexpressing lungs. This neutrophilia was inhibited by a cPLA2 inhibitor and a leukotriene B4 inhibitor, but not by dexamethasone.
Conclusion
Gln deficiency leads to the impairment of MKP-1 induction and activation of p38 MAPK and cPLA2, resulting in the augmentation of neutrophilic, more so than eosinophilic, airway inflammation.
논문정보
- Research article
- 2021년 10월 (BRIC 등록일 2021-10-08)
- 국내 연구진
- 의약학 > 면역의학
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