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- Title
The prolactin receptor is expressed in rheumatoid arthritis and psoriatic arthritis synovial tissue and contributes to macrophage activation.
- Authors
Man Wai Tang; Reedquist, Kris A.; Garcia, Samuel; Malvar Fernandez, Bea; Codullo, Veronica; Vieira-Sousa, Elsa; Goffin, Vincent; Reuwer, Anne Q.; Twickler, Marcel T.; Gerlag, Daniëlle M.; Tak, Paul-Peter
- Abstract
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 23kDa PRL levels were measured in 119 RA patients using a fluoroimmuno-metric 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.
- Subjects
CELL receptors; CHI-squared test; STATISTICAL correlation; ENZYME-linked immunosorbent assay; FISHER exact test; GENE expression; IMMUNOHISTOCHEMISTRY; MACROPHAGES; POLYMERASE chain reaction; PROLACTIN; PSORIATIC arthritis; QUESTIONNAIRES; RESEARCH funding; RHEUMATOID arthritis; STATISTICS; SYNOVIAL membranes; DATA analysis; VISUAL analog scale; DATA analysis software; DESCRIPTIVE statistics; FLUOROIMMUNOASSAY; MANN Whitney U Test; KRUSKAL-Wallis Test
- Publication
Rheumatology, 2016, Vol 55, Issue 12, p2246
- ISSN
1462-0324
- Publication type
Article
- DOI
10.1093/rheumatology/kew316