A critical role for adrenomedullin-calcitonin receptor-like receptor in regulating rheumatoid fibroblast-like synoviocyte apoptosis

The Journal of Immunology : Official Journal of the American Association of Immunologists
Benjamin UzanFrédéric Lioté

Abstract

Rheumatoid arthritis (RA) is characterized by fibroblast-like synoviocyte (FLS) hyperplasia, which is partly ascribable to decreased apoptosis. In this study, we show that adrenomedullin (ADM), an antiapoptotic peptide, is constitutively secreted in larger amounts by FLS from joints with RA (RA-FLS) than with osteoarthritis (OA-FLS). ADM secretion was regulated by TNF-alpha. Peptidylglycine alpha-amidating monooxygenase, the ADM-processing enzyme, was expressed at the mRNA level by both RA-FLS and OA-FLS. Constituents of the ADM heterodimeric receptor calcitonin receptor-like receptor (CRLR)/receptor activity-modifying protein (RAMP)-2 were up-regulated at the mRNA and protein levels in cultured RA-FLS compared with OA-FLS. ADM induced rapid intracellular cAMP production in FLS and reduced caspase-3 activity, DNA fragmentation, and chromatin condensation in RA-FLS exposed to apoptotic conditions, indicating that CRLR/RAMP-2 was fully functional. ADM-induced cAMP production was less marked in OA-FLS than in RA-FLS, suggesting differences in receptor regulation and expression. ADM dose-dependently inhibited RA-FLS apoptosis, and this effect was reversed by the 22-52 ADM antagonist peptide. ADM inhibited RA-FLS apoptosis triggered...Continue Reading

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Citations

Oct 18, 2007·Journal of Cellular Physiology·Benjamin UzanMichèle Cressent
Mar 10, 2011·Acta Physiologica·P A InselA C Zambon
Oct 19, 2011·Arthritis and Rheumatism·Marie-Dominique Ah KioonFrédéric Lioté
Aug 9, 2016·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Linghua LiuZhihong Xiao
Oct 2, 2007·Arthritis and Rheumatism·Hirokazu SawaiCornelia M Weyand
Oct 23, 2013·Molecular Medicine Reports·Changchun FanJinfang Cai
Mar 17, 2017·Journal of Immunology Research·Shotaro TakanoMasashi Takaso
Apr 30, 2015·British Journal of Clinical Pharmacology·David A WalshSara Kelly
Nov 18, 2008·Biochimie·Chin-ju J Hsiao, Susan R Stapleton

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