Galvanic current activates the NLRP3 inflammasome to promote type I collagen production in tendon
- Instituto Murciano de Investigación Biosanitaria, Spain
- University of Murcia, Spain
- MV Clinic, Spain
Abstract
The NLRP3 inflammasome coordinates inflammation in response to different pathogen- and damage-associated molecular patterns, being implicated in different infectious, chronic inflammatory, metabolic and degenerative diseases. In chronic tendinopathic lesions, different non-resolving mechanisms produce a degenerative condition that impairs tissue healing and which therefore complicates their clinical management. Percutaneous needle electrolysis consists of the application of a galvanic current and is an emerging treatment for tendinopathies. In the present study, we found that galvanic current activates the NLRP3 inflammasome and induces an inflammatory response that promotes a collagen-mediated regeneration of the tendon in mice. This study establishes the molecular mechanism of percutaneous electrolysis that can be used to treat chronic lesions and describes the beneficial effects of an induced inflammasome-related response.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 1 to 7.
Article and author information
Author details
Alejandro Peñin-Franch
Fermín Valera-Garrido
Funding
Ministerio de Ciencia, Innovación y Universidades (SAF2017‐88276‐R)
- Pablo Pelegrín
Ministerio de Ciencia, Innovación y Universidades (PID2020-116709RB-I00)
- Pablo Pelegrín
Fundación Séneca (20859/PI/18)
- Pablo Pelegrín
Fundación Séneca (21081/PDC/19)
- Pablo Pelegrín
European Research Council (614578)
- Pablo Pelegrín
European Research Concil (899636)
- Pablo Pelegrín
Ministerio de Ciencia, Innovación y Universidades (PID2020-113919RB-I00)
- Juan M Bueno
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experimental protocols for animal handling were refined and approved by the local animal research ethical committee (references 241/2016 and 541/2019) and Animal Health Service of the General Directorate of Fishing and Farming of the Council of Murcia (Servicio de Sanidad Animal, Dirección General de Ganadería y Pesca, Consejería de Agricultura y Agua de la Región de Murcia, reference A13160702). Animal experimentation was performed in strict accordance with the Hospital Clínico Universitario Vírgen de la Arrixaca animal experimentation guidelines, and the Spanish national (RD 1201/2005 and Law 32/2007) and EU (86/609/EEC and 2010/63/EU) legislation.
Human subjects: We present non-invasive ultrasound scanning images from routinely clinical following from a single patient. The data is completely anonymised and from the normal clinical routine practice.
Copyright
© 2022, Peñin-Franch et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 1,600
- views
-
- 283
- downloads
-
- 15
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Galvanic current activates the NLRP3 inflammasome to promote type I collagen production in tendon
eLife 11:e73675.
https://doi.org/10.7554/eLife.73675
Further reading
-
- Immunology and Inflammation
In autoimmune type 1 diabetes (T1D), immune cells infiltrate and destroy the islets of Langerhans — islands of endocrine tissue dispersed throughout the pancreas. However, the contribution of cellular programs outside islets to insulitis is unclear. Here, using CO-Detection by indEXing (CODEX) tissue imaging and cadaveric pancreas samples, we simultaneously examine islet and extra-islet inflammation in human T1D. We identify four sub-states of inflamed islets characterized by the activation profiles of CD8+T cells enriched in islets relative to the surrounding tissue. We further find that the extra-islet space of lobules with extensive islet-infiltration differs from the extra-islet space of less infiltrated areas within the same tissue section. Finally, we identify lymphoid structures away from islets enriched in CD45RA+ T cells — a population also enriched in one of the inflamed islet sub-states. Together, these data help define the coordination between islets and the extra-islet pancreas in the pathogenesis of human T1D.
-
- Cell Biology
- Immunology and Inflammation
The endothelial blood-brain barrier (BBB) strictly controls immune cell trafficking into the central nervous system (CNS). In neuroinflammatory diseases such as multiple sclerosis, this tight control is, however, disturbed, leading to immune cell infiltration into the CNS. The development of in vitro models of the BBB combined with microfluidic devices has advanced our understanding of the cellular and molecular mechanisms mediating the multistep T-cell extravasation across the BBB. A major bottleneck of these in vitro studies is the absence of a robust and automated pipeline suitable for analyzing and quantifying the sequential interaction steps of different immune cell subsets with the BBB under physiological flow in vitro. Here, we present the under-flow migration tracker (UFMTrack) framework for studying immune cell interactions with endothelial monolayers under physiological flow. We then showcase a pipeline built based on it to study the entire multistep extravasation cascade of immune cells across brain microvascular endothelial cells under physiological flow in vitro. UFMTrack achieves 90% track reconstruction efficiency and allows for scaling due to the reduction of the analysis cost and by eliminating experimenter bias. This allowed for an in-depth analysis of all behavioral regimes involved in the multistep immune cell extravasation cascade. The study summarizes how UFMTrack can be employed to delineate the interactions of CD4+ and CD8+ T cells with the BBB under physiological flow. We also demonstrate its applicability to the other BBB models, showcasing broader applicability of the developed framework to a range of immune cell-endothelial monolayer interaction studies. The UFMTrack framework along with the generated datasets is publicly available in the corresponding repositories.
