TRPA1 Mechanoreceptors Mediate the IL-6 Response to a Single PD Dwell in the Rat.

BACKGROUND

The development of modern, biocompatible peritoneal dialysis (PD) fluids has not entirely eliminated the local pro-inflammatory effects of PD fluid administration. The present study was performed in order to establish the importance of known signaling pathways connected to mechano-, osmo- and chemo-sensors of the transient receptor potential (TRP) family for the acute inflammatory response to PD.

METHODS

Rats were exposed to a single 4-hour dwell of lactate-buffered, 2.5% glucose, filter-sterilized PD fluid through an implanted PD catheter. In some groups, the PD dwell was preceded by intravenous administration of blockers of TRPV1 (BCTC), TRPA1 (HC030031), or neurokinin 1 (NK1) (Spantide II) receptors. Cytokine messenger ribonucleic acid (mRNA) expressions were quantified in tissue biopsies (real-time polymerase chain reaction [qPCR]), and cytokine concentrations were quantified in dialysate samples by enzyme-linked immunosorbent assay (ELISA). Tissue expressions of TRPV1, TRPA1, and NK1 were evaluated immuno-histochemically.

RESULTS

The PD dwell induced peritoneal synthesis of , , and and a secretion of interleukin-6 (IL-6) into the dialysate. The catheter implantation already induced the transcription of and but did not significantly affect transcription. The response to the PD dwell could be virtually eliminated by blocking TRPA1 but was not affected by TRPV1 blockade. Blocking the substance P receptor, NK1, produced an insignificant trend towards inhibition. TRPA1 and NK1 showed a stronger immuno-reactivity than TRPV1 on cells of the peritoneal tissue.

CONCLUSION

The results show that IL-6 synthesis and secretion were connected to acute PD fluid exposure, and this response was triggered by TRPA1 receptors, possibly located to non-neuronal cells.