Lysophosphatidic acid receptor 1 suppression sensitizes rheumatoid fibroblast-like synoviocytes to tumor necrosis factor-induced apoptosis

Arthritis and Rheumatism
Beatriz OrosaCarmen Conde

Abstract

To investigate the role of lysophosphatidic acid (LPA) receptors in the proliferation and apoptosis of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). Expression of LPA receptors 1-3 was analyzed by real-time polymerase chain reaction (PCR). LPAR1 and LPAR2 were suppressed in RA FLS by small interfering RNA (siRNA) transfection. Proliferation of RA FLS after tumor necrosis factor (TNF) and LPA stimulation was determined with a luminescent cell viability assay. Apoptosis was analyzed by quantification of nucleosome release and measurement of activated caspase 3/7. Genes involved in the apoptotic response were identified with a human apoptosis PCR array and validated with Western blot assays. The requirement of these genes for apoptosis sensitization was assessed by siRNA transfection. Secretion of mediators of inflammation was analyzed by enzyme-linked immunosorbent assay. Only LPAR1 and LPAR2 were expressed by RA FLS, and their levels were higher than those in osteoarthritis (OA) FLS. Suppression of LPAR1 abrogated TNF-induced proliferation and sensitized the RA FLS, but not the OA FLS, to TNF-induced apoptosis. These changes occurred despite an increased early inflammatory response to TNF. Sens...Continue Reading

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Citations

Mar 22, 2014·PloS One·Marta Krystyna KosinskaJuergen Steinmeyer
Mar 15, 2013·Annals of the Rheumatic Diseases·Beatriz OrosaCarmen Conde
Mar 6, 2013·Biochemical and Biophysical Research Communications·Pasha Hadidi, Kyriacos A Athanasiou
Aug 25, 2015·European Journal of Pharmacology·Beatriz OrosaCarmen Conde
Jul 6, 2014·Journal of Bone and Mineral Metabolism·Beatriz OrosaCarmen Conde
Aug 16, 2013·Journal of Biomolecular Screening·Stephen L Garland
Dec 13, 2018·Physiology·Jeffrey C Horowitz, Victor J Thannickal
Oct 28, 2019·Cancers·Eleanna KaffeVassilis Aidinis
Dec 6, 2019·The Journal of Pharmacology and Experimental Therapeutics·Nerea MosqueraCarmen Conde
Mar 15, 2018·International Journal of Molecular Sciences·Liv Weichien ChenLing-Jun Ho
Nov 30, 2019·Evidence-based Complementary and Alternative Medicine : ECAM·Hui WangZhe Chen
Sep 1, 2019·Journal of Autoimmunity·Christiana MagkriotiVassilis Aidinis

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis