000			nab a22 7a 4500
999			_c17137 _d17137
003			PC17137
005			20230123121847.0
008			230123b xxu||||| |||| 00| 0 eng d
040			_cH12O
041			_aeng
100			_91880 _aCriado Carrasco, Gabriel _eInstituto de Investigación i+12
100			_91010 _aPablos Álvarez, José Luis _eReumatología
245	0	0	_aMacrophages from the synovium of active rheumatoid arthritis exhibit an activin A-dependent pro-inflammatory profile. _h[artículo]
260			_bThe Journal of pathology, _c2015
300			_a235(3):515-26.
500			_aFormato Vancouver: Soler Palacios B, Estrada Capetillo L, Izquierdo E, Criado G, Nieto C, Municio C et al. Macrophages from the synovium of active rheumatoid arthritis exhibit an activin A-dependent pro-inflammatory profile. J Pathol. 2015 Feb;235(3):515-26.
501			_aPMID: 25319955
504			_aContiene 50 referencias
520			_aRheumatoid arthritis (RA) is a chronic inflammatory disease whose pathogenesis and severity correlates with the presence of macrophage-derived pro-inflammatory cytokines within the inflamed synovium. Macrophage-derived cytokines fuel the pathological processes in RA and are targets of clinically successful therapies. However, although macrophage polarization determines cytokine production, the polarization state of macrophages in RA joints remains poorly defined. To dissect the molecular basis for the tissue-damaging effects of macrophages in RA joints, we undertook the phenotypic and transcriptomic characterization of ex vivo isolated CD14(+) RA synovial fluid (RA-SF) macrophages. Flow cytometry and gene profiling indicated that RA-SF macrophages express pro-inflammatory polarization markers (MMP12, EGLN3, CCR2), lack expression of markers associated with homeostatic and anti-inflammatory polarization (IGF1, HTR2B) and exhibit a transcriptomic profile that resembles the activin A-dependent gene signature of pro-inflammatory in vitro-generated macrophages. In fact, high levels of Smad-activating activin A were found in RA-SF and, accordingly, the Smad signalling pathway was activated in ex vivo-isolated RA-SF macrophages. In vitro experiments on monocytes and macrophages indicated that RA-SF promoted the acquisition of pro-inflammatory markers (INHBA, MMP12, EGLN3, CCR2) but led to a significant reduction in the expression of genes associated with homeostasis and inflammation resolution (FOLR2, SERPINB2, IGF1, CD36), thus confirming the pro-inflammatory polarization ability of RA-SF. Importantly, the macrophage-polarizing ability of RA-SF was inhibited by an anti-activin A-neutralizing antibody, thus demonstrating that activin A mediates the pro-inflammatory macrophage-polarizing ability of RA-SF. Moreover, and in line with these findings, multicolour immunofluorescence evidenced that macrophages within RA synovial membranes (RA-SM) also express pro-inflammatory polarization markers whose expression is activin A-dependent. Altogether, our results demonstrate that macrophages from RA synovial fluids and membranes exhibit an MMP12(+) EGLN3(+) CCR2(+) pro-inflammatory polarization state whose acquisition is partly dependent on activin A from the synovial fluid.
710			_9123 _aServicio de Reumatología
710			_9625 _aInstituto de Investigación imas12
856			_uhttp://pc-h12o-es.m-hdoct.a17.csinet.es/pdf/pc/1/pc17137.pdf _ySolicitar documento
942			_2ddc _cART _n0