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27-hydroxycholesterol roles in respiratory disease pathogenesis.
Ya Li1, Jiaqi Yan2, Chuanwang Song1
1Department of Immunology, School of Laboratory Medicine, Bengbu Medical University, Anhui 233030, China; Anhui Province Key Laboratory of Immunology in Chronic Diseases, Bengbu Medical University, Anhui 233030, China.
International Immunopharmacology
|September 5, 2025
Summary
27-Hydroxycholesterol (27-HC), a cholesterol metabolite, worsens asthma and lung cancer by promoting inflammation and cell growth. Targeting 27-HC offers a promising therapeutic strategy for respiratory diseases.
Area of Science:
- Biochemistry
- Molecular Biology
- Pathology
Background:
- 27-Hydroxycholesterol (27-HC) is an endogenous cholesterol metabolite produced by sterol 27-hydroxylase (CYP27A1).
- 27-HC regulates cholesterol homeostasis by inhibiting sterol regulatory element-binding protein 2 (SREBP-2).
- 27-HC interacts with liver X receptors (LXR) and estrogen receptors (ER), acting as a selective estrogen receptor modulator (SERM).
Purpose of the Study:
- To investigate the biological effects of 27-HC in respiratory diseases.
- To elucidate the role of 27-HC in asthma pathogenesis.
- To examine the impact of 27-HC on lung cancer progression.
Main Methods:
- Literature review of studies on 27-HC.
- Analysis of 27-HC's molecular interactions with LXR and ER.
- Evaluation of 27-HC's effects on airway inflammation, remodeling, and cancer cell behavior.
Main Results:
- 27-HC exacerbates asthma by promoting airway inflammation and remodeling.
- 27-HC enhances lung cancer cell proliferation, invasion, and metastasis.
- 27-HC acts as a SERM, with context-dependent ER agonistic or antagonistic activity.
Conclusions:
- 27-HC plays a significant role in the pathogenesis of respiratory diseases.
- Targeting 27-HC presents a potential therapeutic avenue for asthma and lung cancer.
- Further research into 27-HC modulation could lead to novel treatments for respiratory conditions.
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