Lidocaine inhibits epithelial chemokine secretion via inhibition of nuclear factor kappa B activation

Abstract

Aim: To study the antiinflammatory effect of lidocaine in intestinal epithelial cells.

Methods: HT-29 and T-84 cells were grown in culture with and without TNF-alpha, lidocaine, aconitine and veratridine. The secretion of IL-8 and IP-10 was measured by ELISA. A cDNA microarray was used to assess gene expression. Real-time PCR was used to confirm the results. Western blots and a modified electromobility shift assay (EMSA) were used to assess NFkappaB activation.

Results: Lidocaine inhibited spontaneous and TNF-alpha induced secretion of IL-8 and IP-10. The combination of veratridine or aconitine, voltage-gated sodium channels (VGSC) agonists that open VGSCs, with lidocaine did not alter the effect of lidocaine on cytokine secretion. Gene array analysis revealed that IkappaB transcription was induced by TNF-alpha and inhibited by lidocaine. IkappaB real-time PCR confirmed this observation. A Western blot analysis demonstrated that the degradation of IkappaB following TNF-alpha treatment was markedly inhibited by lidocaine. Lidocaine treatment resulted in decreased generation of phosphorylated IkappaB. A modified EMSA was complementary and demonstrated marked inhibition of NFkappaB nuclear binding.

Conclusion: Lidocaine inhibits IL-8 and IP-10 secretion from intestinal cells. This effect is mediated by inhibition of NFkappaB activation via decreased IkappaB phosphorylation and is not mediated by lidocaine's effect on VGSC.