Pro-inflammatory cytokines up-regulate and sensitize metabotropic and ionotropic cannabinoid receptors in rheumatoid arthritis and osteoarthritis synovial fibroblasts

Lowin, Torsten; Späth, T; Straub, Rainer H.

doi:10.1016/j.bbi.2015.06.034

Cited by 1 publication

(1 citation statement)

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“…Inflammation occurring in many neurodegenerative diseases, such as multiple sclerosis and Alzheimer's disease, leads to changes in the cellular environment that will favor the activation of oligodendrocyte TRPA1. Endogenous substances that increase TRPA1 expression and activity include reactive oxygen and nitrogen species (Kozai et al, 2014 ; Sullivan et al, 2015 ), hypoxia and hyperoxia (Takahashi et al, 2011 ), and cytokines such as interferon gamma, interleukin 1 beta and tumor necrosis factor‐alpha (Lowin et al, 2015 ). Environmental irritants that can cause demyelination or oligodendrocyte apoptosis (Birgbauer et al, 2004 ; Brambrink et al, 2012 ; Davies et al, 2000 ; Shi et al, 2011 , 2015 ; Tian et al, 2020 ), have also been shown to activate TRPA1, including acrolein (Leishman et al, 2017 ; Park et al, 2015 ), toluene (Taylor‐Clark et al, 2009 ), lysophosphatidylcholine (Tian et al, 2020 ) and isoflurane (Ton et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Transient receptor potential Ankyrin‐1 (TRPA1) agonists suppress myelination and induce demyelination in organotypic cortical slices

Giacco

Flower

Artamonova

et al. 2023

Glia

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Oligodendrocytes are highly specialized glial cells characterized by their production of multilayer myelin sheaths that wrap axons to speed up action potential propagation. It is due to their specific role in supporting axons that impairment of myelin structure and function leads to debilitating symptoms in a wide range of degenerative diseases, including Multiple Sclerosis and Leukodystrophies. It is known that myelin damage can be receptor‐mediated and recently oligodendrocytes have been shown to express Ca2+‐permeable Transient Receptor Potential Ankyrin‐1 (TRPA1) channels, whose activation can result in myelin damage in ischemia. Here, we show, using organotypic cortical slice cultures, that TRPA1 activation, by TRPA1 agonists JT010 and Carvacrol for varying lengths of time, induces myelin damage. Although TRPA1 activation does not appear to affect oligodendrocyte progenitor cell number or proliferation, it prevents myelin formation and after myelination causes internodal shrinking and significant myelin degradation. This does not occur when the TRPA1 antagonist, A967079, is also applied. Of note is that when TRPA1 agonists are applied for either 24 h, 3 days or 7 days, axon integrity appears to be preserved while mature myelinated oligodendrocytes remain but with significantly shortened internodes. These results provide further evidence that TRPA1 inhibition could be protective in demyelination diseases and a promising therapy to prevent demyelination and promote remyelination.

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