The prolactin receptor is expressed in rheumatoid arthritis and psoriatic arthritis synovial tissue and contributes to macrophage activation.
OBJECTIVE
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.
Division of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands, m.w.tang@amc.uva.nl.|Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, the Netherlands.
Man Wai
MW
Tang
Division of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.|Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, the Netherlands.
Kris A
KA
Reedquist
Division of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.|Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, the Netherlands.
Samuel
S
Garcia
Division of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.|Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, the Netherlands.
Bea Malvar
BM
Fernandez
Division of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
Veronica
V
Codullo
Division of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
Elsa
E
Vieira-Sousa
Inserm, Inserm U1151, Institut Necker Enfants Malades, Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Vincent
V
Goffin
Division of Vascular Medicine, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
Anne Q
AQ
Reuwer
Division of Vascular Medicine, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
Marcel T
MT
Twickler
Division of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
Daniëlle M
DM
Gerlag
Division of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
Paul-Peter
PP
Tak
D015703:Antigens, CD / Q000378:metabolism; D015535:Arthritis, Psoriatic / Q000276:immunology / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008262:Macrophage Activation / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011981:Receptors, Prolactin / Q000378:metabolism*; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation
D015703:Antigens, CD; D016207:Cytokines; D012333:RNA, Messenger; D011981:Receptors, Prolactin
cell receptor interaction; hormones; macrophages; rheumatoid arthritis; signalling and activation; synovium