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Neuropeptides activate TRPV1 in rheumatoid arthritis fibroblast-like synoviocytes and foster IL-6 and IL-8 production
  1. Riccardo Terenzi1,
  2. Eloisa Romano1,
  3. Mirko Manetti1,2,
  4. Francesca Peruzzi1,
  5. Francesca Nacci1,
  6. Marco Matucci-Cerinic1,
  7. Serena Guiducci1
  1. 1 Department of Biomedicine, Division of Rheumatology, University of Florence, Florence, Italy
  2. 2 Department of Anatomy, Histology and Forensic Medicine, Section of Anatomy, University of Florence, Florence, Italy
  1. Correspondence to : Dr Serena Guiducci, Department of Biomedicine, Division of Rheumatology, University of Florence, Viale Pieraccini 18, Florence I-50139, Italy; s.guiducci{at}

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Neurogenic inflammation is caused by neuropeptides which are released by peripheral neurons and induce inflammatory signals. Two of the main neuropeptides involved are substance P (SP) and calcitonin gene related peptide (CGRP),1 both acting through several molecular mechanisms including activation of transient receptor potential vanilloid (TRPV) cation channels, particularly TRPV1 (also called vanilloid receptor type 1 or capsaicin (CAP) receptor).2 ,3 SP and CGRP have been found increased in synovial fluid from rheumatoid arthritis (RA) patients4 ,5 and may induce the production of interleukin (IL)-6 and IL-8 in RA synoviocytes,6 suggesting that neuropeptides may have a role in joint inflammation during RA. Interestingly, TRPV cation channels are expressed in various non-neuronal cell types and, recently, they have been found expressed in human synoviocytes.7

No previous study has investigated the possible link among SP, CGRP and TRPV channels in the inflammation process driven by RA synoviocytes. The aim of our work was to investigate whether SP, CGRP and CAP, a potent activator (agonist) of TRPV1, can increase IL-6 and IL-8 production by RA and healthy fibroblast-like synoviocytes, and whether neuropeptides may modulate TRPV1 expression in RA and healthy cells. Synoviocytes were obtained from knee-biopsy of three patients with active RA diagnosed according to the American College of Rheumatology 1987 revised criteria undergoing surgical joint replacement. Patients had not received any disease-modifying antirheumatic drug treatment. Healthy synoviocytes were collected from knee-biopsy of three subjects who underwent surgical intervention after accidental trauma. Synoviocytes (passage 2–4) were cultured at confluence, serum-starved for 24 h and incubated for …

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  • *RT and ER contributed equally.

  • Contributors All authors were involved in drafting the article or revising it critically for important intellectual content and all authors approved the final version to be published. RT, ER, MM, MM-C, SG: Study conception and design; RT, ER, MM, FP, FN, MM-C, SG: Acquisition of data; RT, ER, MM, SG: Analysis and interpretation of data.

  • Funding This study has been supported by grants from the University of Florence (Progetti di Ricerca di Ateneo, ex 60% to M. Matucci-Cerinic).

  • Competing interests None.

  • Patient consent Obtained. All subjects gave written informed consent.

  • Ethics approval The study was approved by the Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.