Up-regulation of NaV1.7 sodium channels expression by tumor necrosis factor-α in cultured bovine adrenal chromaffin cells and rat dorsal root ganglion neurons

Ryuji Tamura, Takayuki Nemoto, Toyoaki Maruta, Shin Onizuka, Toshihiko Yanagita, Akihiko Wada, Manabu Murakami, Isao Tsuneyoshi
Anesthesia and Analgesia 2014, 118 (2): 318-24

BACKGROUND: Tumor necrosis factor-α (TNF-α) is not only a key regulator of inflammatory response but also an important pain modulator. TNF-α enhances both tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant Na channel currents in dorsal root ganglion (DRG) neurons. However, it remains unknown whether TNF-α affects the function and expression of the TTX-S NaV1.7 Na channel, which plays crucial roles in pain generation.

METHODS: We used cultured bovine adrenal chromaffin cells expressing the NaV1.7 Na channel isoform and compared them with cultured rat DRG neurons. The expression of TNF receptor 1 and 2 (TNFR1 and TNFR2) in adrenal chromaffin cells was studied by Semiquantitative reverse transcription-polymerase chain reaction. The effects of TNF-α on the expression of NaV1.7 were examined with reverse transcription-polymerase chain reaction and Western blot analysis. Results were expressed as mean ± SEM.

RESULTS: TNFR1 and TNFR2 were expressed in adrenal chromaffin cells, as well as reported in DRG neurons. TNF-α up-regulated NaV1.7 mRNA by 132% ± 9% (N = 5, P = 0.004) in adrenal chromaffin cells, as well as 117% ± 2% (N = 5, P < 0.0001) in DRG neurons. Western blot analysis showed that TNF-α increased NaV1.7 protein up to 166% ± 24% (N = 5, corrected P < 0.0001) in adrenal chromaffin cells, concentration- and time-dependently.

CONCLUSIONS: TNF-α up-regulated NaV1.7 mRNA in both adrenal chromaffin cells and DRG neurons. In addition, TNF-α up-regulated the protein expression of the TTX-S NaV1.7 channel in adrenal chromaffin cells. Our findings may contribute to understanding the peripheral nociceptive mechanism of TNF-α.

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