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TRPA1 mechanoreceptors mediate the IL-6 response to a single PD dwell in the rat

Artikel i vetenskaplig tidskrift
Författare Daniel Nilsson
Eva Jennische
Nicola Cavallini
Magnus Braide
Publicerad i Peritoneal Dialysis International
Volym 37
Nummer/häfte 5
Sidor 509-515
ISSN 0896-8608
Publiceringsår 2017
Publicerad vid Institutionen för biomedicin
Sidor 509-515
Språk en
Länkar doi.org/10.3747/pdi.2016.00290
Ämnesord IL-6, Inflammation, NK1, Peritoneal dialysis, Rats, TRPA1
Ämneskategorier Annan medicinsk grundvetenskap

Sammanfattning

♦ 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 Il1b, Tnf, and Il6 and a secretion of interleukin-6 (IL-6) into the dialysate. The catheter implantation already induced the transcription of Il1b and Tnf but did not significantly affect Il6 transcription. The Il6 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 Il6 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. © 2017 International Society for Peritoneal Dialysis.

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