Details

Autor(en) / Beteiligte

• Long, Jiangwen
• Zhao, Wang
• Xiang, Yangen
• Wang, Yufei
• Xiang, Wei
• Liu, Xueting
• Jiang, Manli
• Song, Yinghui
• Hu, Jinyue

Titel

STAT3 promotes cytoplasmic-nuclear translocation of RNA-binding protein HuR to inhibit IL-1β-induced IL-8 production

Ist Teil von

• International immunopharmacology, 2024-05, Vol.133, p.112065-112065, Article 112065

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• •STAT3 inhibition up-regulate IL-1β-induced IL-8.•STAT3 inhibition does not up-regulate IL-1β-induced signaling.•STAT3 inhibition increases the stabilization of IL-8 mRNA.•STAT3 inhibition induces HuR re-localization to cytoplasm.•IL-6 activation of STAT3 induces HuR cytoplasmic-nuclear transport. Signal transducer and activator of transcription 3 (STAT3) functions to regulate inflammation and immune response, but its mechanism is not fully understood. We report here that STAT3 inhibitors Stattic and Niclosamide up-regulated IL-1β-induced IL-8 production in C33A, CaSki, and Siha cervical cancer cells. As expected, IL-1β-induced IL-8 production was also up-regulated through the molecular inhibition of STAT3 by use of CRISPR/Cas9 technology. Unexpectedly, IL-1β induced IL-8 production via activating ERK and P38 signal pathways, but neither STAT3 inhibitors nor STAT3 knockout affected IL-1β-induced signal transduction, suggesting that STAT3 decreases IL-8 production not via inhibition of signal transduction. To our surprise, STAT3 inhibition increased the stabilization, and decreased the degradation of IL-8 mRNA, suggesting a post-transcriptional regulation of IL-1β-induced IL-8. Moreover, Dihydrotanshinone I, an inhibitor of RNA-binding protein HuR, down-regulated IL-1β-induced IL-8 dose-dependently. HuR inhibition by CRISPR/Cas9 also decreased IL-8 production induced by IL-1β. Mechanistically, co-immunoprecipitation results showed that STAT3 did not react with HuR directly, but STAT3 inhibition increased the protein levels of HuR in cytoplasm. And IL-6 activation of STAT3 induced HuR cytoplasmic-nuclear transport. Taken together, these results suggest that STAT3 contributes to HuR nuclear localization and inhibits Il-1β-induced IL-8 production through this non-transcriptional mechanism.