KIF2A decreases IL-33 production and attenuates allergic asthmatic inflammation
Zhengxia Wang1, Jingjing Wu1, Jingxian Jiang1
1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Background:
The microtubule-dependent molecular motor protein Kinesin Family Member 2A (KIF2A) is down-regulated in asthmatic human airway epithelium. However, little is known about the roles of KIF2A as well as the possible underlying mechanisms in asthma.
Methods:
House dust mite (HDM) extract was administered to establish a murine model of asthma. The expression of KIF2A, IL-33 and the autophagy pathways were detected. The plasmid pCMV-KIF2A was used to overexpress KIF2A in the airway epithelial cells in vitro and in vivo. IL-4, IL-5, IL-33 and other cytokines in bronchoalveolar lavage fluid (BALF) and lung tissues homogenates were measured.
Results:
In response to the challenge of house dust mite (HDM) in vitro and in vivo, airway epithelial cells displayed decreased production of KIF2A. Meanwhile, autophagy and IL-33 were increased in HMD-treated epithelial cells. Mechanistically, KIF2A decreased autophagy via suppressing mTORC1 pathway in HDM-treated epithelial cells, which contributed to the reduced production of IL-33. Moreover, in vivo KIF2A transfection reduced IL-33 and autophagy in the lung, leading to the attenuation of allergic asthma.
Conclusion:
KIF2A suppressed mTORC1-mediated autophagy and decreased the production of epithelial-derived cytokine IL-33 in allergic airway inflammation. These data indicate that KIF2A may be a novel target in allergic asthma.
Insights
Kinesin Family Member 2A (KIF2A) is reduced in asthma. Restoring KIF2A suppresses autophagy and IL-33, potentially treating allergic airway inflammation.
Area of Science:
- Cell Biology
- Immunology
- Respiratory Medicine
Background:
- Kinesin Family Member 2A (KIF2A) is downregulated in asthmatic airway epithelium.
- The precise role and mechanisms of KIF2A in asthma remain largely unknown.
Purpose of the Study:
- To investigate the role of KIF2A in a murine model of allergic asthma.
- To elucidate the underlying molecular mechanisms involving autophagy and IL-33.
Main Methods:
- Established a house dust mite (HDM)-induced asthma model in mice.
- Assessed KIF2A expression, autophagy markers, and IL-33 levels.
- Utilized KIF2A overexpression plasmid (pCMV-KIF2A) in vitro and in vivo.
- Measured cytokine levels (IL-4, IL-5, IL-33) in bronchoalveolar lavage fluid and lung homogenates.
Main Results:
- HDM challenge decreased KIF2A expression in airway epithelial cells.
- HDM exposure increased autophagy and IL-33 production.
- KIF2A suppressed mTORC1-mediated autophagy, reducing IL-33 production.
- In vivo KIF2A delivery attenuated lung inflammation, IL-33, and autophagy.
Conclusions:
- KIF2A inhibits mTORC1-autophagy and epithelial IL-33 production in allergic airway inflammation.
- KIF2A represents a potential therapeutic target for allergic asthma.
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