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Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum
Published on: May 3, 2024
GATA1-activated lncRNA OIP5-AS1 and GAS5 promote pyroptosis to exacerbate asthma through regulating miR-136-5p/LIFR
Suzhi Zhao1, Sini Huang1, Yawei Wu1
1Department of Pulmonary and Critical Care Medicine, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, People's Republic of China.
Abstract:
Pyroptosis plays a pivotal role in airway epithelial inflammation during the progression of asthma. This study aimed to explore the influence and mechanisms of opa-interacting protein 5 antisense RNA1 (OIP5-AS1) and growth arrest-specific transcript 5 (GAS5) on pyroptosis in asthmatic models. Pyroptosis was induced in Dermatophagoides pteronyssinus 1 (Der p1)-exposed 16HBE cells and ovalbumin (OVA)-challenged rats. Subsequently, pyroptosis and its related molecular mechanisms were investigated. Our results indicated that GATA1, OIP5-AS1, GAS5, and LIFR were upregulated, while miR-136-5p was downregulated in the patients and experimental models of asthma. OIP5-AS1/GAS5 knockdown repressed NLRP3 inflammasome-mediated pyroptosis in 16HBE cells. Mechanistically, OIP5-AS1/GAS5 sponged miR-136-5p to enhance LIFR expression and subsequently activated NF-κB pathway. OIP5-AS1, GAS5, or LIFR-mediated induction of pyroptosis was abrogated by miR-136-5p mimics or NF-κB inhibitors (BAY11-7082). Finally, GATA1 transcriptionally activated OIP5-AS1/GAS5 to trigger pyroptosis, thereby driving asthma progression in vivo and in vitro. In conclusion, OIP5-AS1/GAS5 transcriptionally activated by GATA1 promoted NLRP3 inflammasome-mediated pyroptosis via the modulation of miR-136-5p/LIFR/NF-κB axis and consequently resulted in airway inflammation in asthma. Our results may provide novel therapeutic strategies for asthma.
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