Cytosolic phospholipase A2 regulates TNF-induced production of joint destructive effectors in synoviocytes

PloS One
Randi M SommerfeltBerit Johansen

Abstract

Rheumatoid arthritis (RA) is an inflammatory disease of the joint characterized by chronic synovitis causing pain, swelling and loss of function due to destruction of cartilage and bone. The complex series of pathological events occurring in RA is largely regulated via excessive production of pro-inflammatory cytokines, the most prominent being tumor necrosis factor (TNF). The objective of this work was to elucidate possible involvement of group IVA cytosolic phospholipase A2 (cPLA2α) in TNF-induced regulation of synovitis and joint destructive effectors in RA, to evaluate the potential of cPLA2α as a future therapeutic target. The involvement of cPLA2α in tumor necrosis factor (TNF)-induced intracellular signaling cascades in synoviocytes (synovial fibroblast-like cells) was analyzed by arachidonic acid (AA) release assay, synoviocyte enzyme activity assay, gene expression analysis by real-time PCR and ELISA immunoassay for the detection of prostaglandin E2 (PGE2), interleukin 8 (IL8) and stromelysin-1 (MMP3), respectively. Inhibitors of cPLA2α enzyme activity (AVX002, ATK) significantly reduced TNF-induced cellular release of AA, PGE2, IL8 and MMP3. This reduction was evident both at transcriptional, protein or metabolite lev...Continue Reading

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Citations

Jun 11, 2014·Nature Reviews. Rheumatology·Louis TongSalvatore Albani
Aug 20, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Eva ArnoldMichael Wink
Aug 26, 2014·Journal of Medicinal Chemistry·George KokotosBerit Johansen
Apr 22, 2015·PloS One·Randi M SommerfeltBerit Johansen
Apr 21, 2017·Food & Function·Maria Luisa CastejónCatalina Alarcón-de-la-Lastra
Oct 27, 2018·The British Journal of Nutrition·María Ángeles RosilloMarina Sánchez-Hidalgo
Sep 10, 2020·International Journal of Molecular Sciences·Antonella BonettiFulvia Ortolani

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Methods Mentioned

BETA
ELISA
PCR
ELISAs

Software Mentioned

LinRegPCR
Ascent
SPSS Statistics
Mx3000P
Multiscan
REST

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