Objectives. Prolactin (PRL) is a lactation-inducing hormone with immunomodulatory properties and is found at elevated levels in the serum of patients with RA and other rheumatic diseases. The PRL receptor (PRLR) has been shown to be expressed by macrophages in atherosclerotic plaques. The aim of this study was to examine PRLR expression by synovial macrophages and its role in the regulation of macrophage activation.Methods. Serum monomeric 23 kDa PRL levels were measured in 119 RA patients using a fluoroimmunometric assay. PRLR expression was assessed in synovial tissue of 91 RA, 15 PsA and 8 OA patients by immunohistochemistry and digital image analysis. Double IF was used to identify PRLR-expressing cells. The effects of PRL on monocyte-derived macrophage gene expression were examined by quantitative real-time PCR and ELISA.Results. Serum PRL levels were similar in female and male RA patients. Median (interquartile range) PRLR expression was significantly higher (P < 0.05) in RA and PsA synovial tissue compared with OA. PRLR colocalized with synovial CD68+ macrophages and von Willebrand factor+ endothelial cells. In vitro, PRLR was prominently expressed in IFN-γ-and IL-10-polarized macrophages compared with other polarizing conditions. PRL by itself had negligible effects on macrophage gene expression, but cooperated with CD40L and TNF to increase expression of pro-inflammatory genes including IL-6, IL-8 and IL-12β.Conclusions. Synovial PRLR expression is enhanced in patients with inflammatory arthritis compared with OA, and PRL cooperates with other pro-inflammatory stimuli to activate macrophages. These results identify PRL and PRLR as potential new therapeutic targets in inflammatory arthritis.
Acetylator phenotype has been determined with sulphamethazine (sulphadimidine) in 69 Spanish patients with rheumatoid arthritis (48 females), all of whom were on second line therapy, and in 96 age-matched normal controls (54 females). Thirty-two patients (46.4%) and 56 controls (58.3%) were classified as slow acetylators. On analysing separately the females in both groups, 37.5% of patients and 63% of controls were found to be slow acetylators. No difference was found in the males (patients 66.3% and controls 52.4% slow acetylators). Rapid acetylator phenotype may be a risk factor for the development of severe rheumatoid arthritis in women.
Background Tie2 is a tyrosine kinase receptor that has an essential role in blood vessel remodeling and angiogenesis, through its activation by its ligands angiopoietin (Ang)-1 and Ang-2. Tie2 and its ligands are expressed in RA synovial tissue, and we have reported that Ang-1 signaling to Tie2 promotes disease persistence and progression in early RA. Furthermore, we have found recently that Tie2 is mainly expressed and activated in RA synovial macrophages, that Ang-2 plays a crucial role in murine arthritis, and that Tie2 signaling promotes the inflammatory activation of monocyte-derived macrophages (MDM). However, the effect of Tie2 signaling on macrophages from arthritis patients has not been assessed yet. Objectives The aim of this study was to examine how complex differentiation stimuli present in the RA and PsA synovial microenvironment might regulate Tie2 expression and signaling on macrophages, as well as the role of Tie2 signaling in macrophages from RA and PsA patients. Methods Human peripheral blood mononuclear cells (PBMCs) were isolated from blood buffy coats (HD) and from RA and PsA patients. Monocytes were differentiated into macrophages in the presence the pro-inflammatory cyokine interferon- gamma (IFN-γ), the anti-inflammatory cytokine interleukin-10 (IL-10), or in the presence of RA or PsA patient synovial fluid (SF). At day 6, Tie-2 expression was analyzed by flow cytometry and quantitative PCR. At day 7, differentiated macrophages were stimulated with TNF in the presence or absence of Ang-1 or Ang-2 and macrophage gene expression of inflammatory mediators and angiogenic factors was analyzed by quantitative PCR. Results Tie2 protein and mRNA expression was observed in HD macrophages differentiated in RA and PsA SF and expression levels where similar to those found in IL-10 and IFN-γ -differentiated HD macrophages. Gene expression analysis of angiogenic factors demonstrated distinct expression profiles under each polarization condition, although unsupervised clustergram analysis demonstrated a high relationship between IL-10, RA SF and PsA SF -differentiated HD macrophages. TNF stimulation of RA SF and PsA SF –differentiated HD macrophages, enhanced expression of the pro-inflammatory cytokines IL-6, IL-8 and TNF and the chemokines CCL-3, CXCL-2, 3, 5, 6 10 and 11, and Ang-1 and Ang-2 stimulation significantly enhanced TNF-driven expression of IL-6, IL-8, CCL-3, CXCL-2, 3, and 6. In RA and PsA patient macrophages differentiated in IL-10 and IFN-γ, Ang-1 and Ang-2 stimulation significantly synergized with TNF to enhance the expression of IL-6, IL-12B, IL-8, CCL-3 and CXCL-6. Conclusions Our results demonstrate that Tie2 is functionally expressed by both RA and PsA macrophages. In both RA and PsA SF -differentiated HD macrophages, and IL-10 and IFN-γ -differentiated RA and PsA patient macrophages, Ang-1 and Ang-2 stimulation enhances TNF induced pro-inflammatory cytokine and chemokine expression. These results suggest that Tie2 signaling, in combination with TNF, induces a pro-inflammator...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.