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Background <p>Inhibition of CXCL8 has been shown to alleviate small intestinal inflammation and suppress activation of Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway. However, the mechanism of the interaction between the two requires further exploration.</p> Methods <p>Human small intestinal epithelial cells were stimulated with lipopolysaccharide (LPS) to establish an inflammatory model. The expression of pro-inflammatory factors was detected using qRT-PCR. Cell viability and apoptosis in cells treated with LPS or phosphate buffered saline (PBS) were assessed by CCK-8 assay and flow cytometry, respectively. Western blot was conducted to detect the expression of proteins linked to the JAK-STAT signaling pathway. Then, cell viability, apoptosis, and the expression of JAK-STAT pathway-associated protein were compared between si-<i>CXCL8</i>#1 and si-NC groups. Furthermore, after overexpressing <i>STAT1</i> in si-<i>CXCL8</i>#1 group, changes in pro-inflammatory cytokine level, cell viability, and apoptosis were analyzed.</p> Results <p>Compared to the PBS control, LPS stimulation significantly increased apoptosis, promoted the release of pro-inflammatory mediators, upregulated JAK-STAT pathway protein expression, and reduced cell viability. <i>CXCL8</i> silencing (si-<i>CXCL8</i>#1) enhanced cell viability, suppressed the release of pro-inflammatory mediators, decreased apoptosis, and downregulated the level of JAK-STAT signaling protein levels. Importantly, in comparison to the si-<i>CXCL8</i>#1 + oe-NC group, the apoptosis and expression of pro-inflammatory mediators were significantly elevated and cell viability was reduced in the si-<i>CXCL8</i>#1 + oe-<i>STAT1</i> group.</p> Conclusion <p>This study revealed that <i>CXCL8</i> aggravated inflammation in small intestinal epithelial cells by activating the JAK-STAT pathway. Silencing <i>CXCL8</i> alleviated LPS-induced inflammation and improved cell survival, which were reversed by <i>STAT1</i> overexpression. These results highlighted the <i>CXCL8</i>-JAK-STAT axis as a potential therapeutic target for treating IBDs such as Crohn’s disease.</p>

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Targeting CXCL8 alleviates intestinal epithelial inflammation by suppressing the JAK-STAT pathway

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月2日

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  • Xiaolong Wu,
  • Jialing Wu,
  • Junmin Xu,
  • Biqin Chen,
  • Jintao Jiang,
  • Xurui Sun,
  • Zengjie Chi

摘要

Background

Inhibition of CXCL8 has been shown to alleviate small intestinal inflammation and suppress activation of Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway. However, the mechanism of the interaction between the two requires further exploration.

Methods

Human small intestinal epithelial cells were stimulated with lipopolysaccharide (LPS) to establish an inflammatory model. The expression of pro-inflammatory factors was detected using qRT-PCR. Cell viability and apoptosis in cells treated with LPS or phosphate buffered saline (PBS) were assessed by CCK-8 assay and flow cytometry, respectively. Western blot was conducted to detect the expression of proteins linked to the JAK-STAT signaling pathway. Then, cell viability, apoptosis, and the expression of JAK-STAT pathway-associated protein were compared between si-CXCL8#1 and si-NC groups. Furthermore, after overexpressing STAT1 in si-CXCL8#1 group, changes in pro-inflammatory cytokine level, cell viability, and apoptosis were analyzed.

Results

Compared to the PBS control, LPS stimulation significantly increased apoptosis, promoted the release of pro-inflammatory mediators, upregulated JAK-STAT pathway protein expression, and reduced cell viability. CXCL8 silencing (si-CXCL8#1) enhanced cell viability, suppressed the release of pro-inflammatory mediators, decreased apoptosis, and downregulated the level of JAK-STAT signaling protein levels. Importantly, in comparison to the si-CXCL8#1 + oe-NC group, the apoptosis and expression of pro-inflammatory mediators were significantly elevated and cell viability was reduced in the si-CXCL8#1 + oe-STAT1 group.

Conclusion

This study revealed that CXCL8 aggravated inflammation in small intestinal epithelial cells by activating the JAK-STAT pathway. Silencing CXCL8 alleviated LPS-induced inflammation and improved cell survival, which were reversed by STAT1 overexpression. These results highlighted the CXCL8-JAK-STAT axis as a potential therapeutic target for treating IBDs such as Crohn’s disease.