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ZFP36 family expression is suppressed by Th2 cells in asthma, leading to enhanced synthesis of inflammatory cytokines and cell surface molecules. | LitMetric

AI Article Synopsis

  • Asthma is a chronic inflammatory airway condition, where the ZFP36 protein family plays a key role in regulating inflammation, especially related to Th2 cells, which are crucial in asthma's type 2 inflammatory response.
  • The study found that mRNA levels of the ZFP36 family are significantly lower in asthmatic patients compared to healthy individuals, indicating a potential link to increased inflammation.
  • Through various experiments, the research suggests that decreased ZFP36 expression in Th2 cells leads to higher levels of inflammatory cytokines, pointing to ZFP36 as a potential therapeutic target for treating asthma and other inflammatory diseases.

Article Abstract

Asthma is a chronic inflammatory airway disease, in which inflammatory cytokines play a pivotal role. The zinc finger binding protein 36 (ZFP36) family includes ZFP36, ZFP36L1, and ZFP36L2 and is among the RNA-binding proteins (RBPs) reported to cause inflammation. The present study aimed to clarify the roles of the ZFP36 family in asthma, particularly highlighting the relationship between the ZFP36 family and Th2 cells, which are key players in type 2 inflammation in asthma. Real-time PCR analysis revealed the preferential expression of ZFP36 family mRNAs in human white blood cells. Gene expression analysis using public datasets from the GEO database (https://www.ncbi.nlm.nih.gov/gds) showed significantly suppressed expression of ZFP36 family mRNAs in patients with asthma compared to that in healthy controls. Using multiple cytokine assays, Th2 cell transfection with ZFP36 family siRNAs enhanced the expression of inflammatory cytokines IL-8, IFN-γ, CCL3/MIP-1α, CCL4/MIP-1β, and TNF-α and cell surface molecules CCR4 (CD194) and PSGL-1 (CD162). Treatment with IL-2, 4, and 15 significantly suppressed, and corticosteroid significantly enhanced the expressions of ZFP36 family mRNAs by Th2 cells. In conclusion, the ZFP36 family expressed by Th2 cells was suppressed in patients with asthma, leading to the enhanced expression of cytokines and cell surface molecules. Suppressed ZFP36 expression in asthma may be involved in the enhancement of airway inflammation, and the ZFP36 family may be a therapeutic target for inflammatory diseases, including asthma.

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Source
http://dx.doi.org/10.1016/j.cellimm.2024.104859DOI Listing

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