Effects of Imatinib Mesylate (Gleevec) on Human Islet NF-kappaB Activation and Chemokine Production In Vitro
2011

Effects of Imatinib on Human Islet NF-kappaB Activation and Chemokine Production

publication Evidence: moderate

Author Information

Author(s): Mokhtari Dariush, Li Tingting, Lu Tao, Welsh Nils

Primary Institution: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden

Hypothesis

The study aims to investigate the control of NF-kB post-translational modifications exerted by Imatinib and its effects on islet gene expression and chemokine production.

Conclusion

Imatinib promotes a modest activation of NF-kB but prolonged exposure dampens the response to cytokines, potentially reducing islet inflammation.

Supporting Evidence

  • Imatinib increased IκB-α and Ser276-p65 phosphorylation after 20 minutes of exposure.
  • Microarray analysis showed increased expression of inflammatory genes IL-4R, TCF5, DR5, I-TRAF, I-CAM, HSP27, and IL-8 after 4 hours of Imatinib treatment.
  • Prolonged Imatinib exposure reduced cytokine-induced IκB-α and STAT1 phosphorylation.

Takeaway

Imatinib can help islet cells survive better, but if used for too long, it makes them less responsive to inflammation signals.

Methodology

Human islets were treated with Imatinib and analyzed for NF-kB activation and chemokine production using immunoblot analysis, microarray, and flow cytometric bead array.

Limitations

Limited access to human islet material may restrict the sensitivity of the analysis.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0024831

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