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


CONCLUSIONS
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.
Lang
Alon
A
Department of Gastroenterology, Chaim Sheba Medical Center, Tel-Aviv University, Tel-Hashomer 52621, Israel. langa@sheba.health.gov.il
Ben Horin
Shomron
S
Picard
Orit
O
Fudim
Ella
E
Amariglio
Ninette
N
Chowers
Yehuda
Y
D000779:Anesthetics, Local / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018925:Chemokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology; D019073:HT29 Cells; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology; D007422:Intestines / Q000187:drug effects / Q000276:immunology; D008012:Lidocaine / Q000494:pharmacology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000779:Anesthetics, Local; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018925:Chemokines; D016209:Interleukin-8; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D008012:Lidocaine