title: Orphan receptor GPR15/BOB is up-regulated in rheumatoid arthritis.
abstract: Chemokine receptors on leukocytes mediate the recruitment and accumulation of these cells within affected joints in chronic inflammatory diseases such as rheumatoid arthritis (RA). Identification of involved receptors offers potential for development of therapeutic interventions. The objective of this study was to investigate the expression of orphan receptor GPR15/BOB in the synovium of RA and non-RA patients and in peripheral blood of RA patients and healthy donors. GPR15/BOB protein and messenger RNA expression were examined in RA and non-RA synovium by immunofluorescence and reverse-transcription polymerase chain reaction (RT-PCR) respectively. GPR15/BOB expression on peripheral blood leukocytes was analysed by flow cytometry and GPR15/BOB messenger RNA was examined in peripheral blood monocytes by RT-PCR. GPR15/BOB protein was observed in CD68+ and CD14+ macrophages in synovia, with greater expression in RA synovia. GPR15/BOB protein was expressed in all patient synovia whereas in non-RA synovia expression was low or absent. Similarly GPR15/BOB messenger RNA was detected in all RA and a minority of non-RA synovia. GPR15/BOB protein was expressed on peripheral blood leukocytes from RA and healthy individuals with increased expression by monocytes and neutrophils in RA. GPR15/BOB messenger RNA expression was confirmed in peripheral blood monocytes. In conclusion GPR15/BOB is expressed by macrophages in synovial tissue and on monocytes and neutrophils in peripheral blood, and expression is up-regulated in RA patients compared to non-RA controls. This orphan receptor on monocytes/macrophages and neutrophils may play a role in RA pathophysiology.
authors.affiliation: Institute of Science and Technology in Medicine, Keele University at Leopold Muller Arthritis Research Centre, RJAH Orthopaedic Hospital, Oswestry, Shropshire, United Kingdom.
authors.forename: Alison
authors.initials: A
authors.lastname: Cartwright
authors.affiliation: Division of Immunity and Infection, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Caroline
authors.initials: C
authors.lastname: Schmutz
authors.affiliation: Institute of Science and Technology in Medicine, Keele University at Leopold Muller Arthritis Research Centre, RJAH Orthopaedic Hospital, Oswestry, Shropshire, United Kingdom.
authors.forename: Ayman
authors.initials: A
authors.lastname: Askari
authors.affiliation: Institute of Science and Technology in Medicine, Keele University at Leopold Muller Arthritis Research Centre, RJAH Orthopaedic Hospital, Oswestry, Shropshire, United Kingdom.
authors.forename: Jan-Herman
authors.initials: JH
authors.lastname: Kuiper
authors.affiliation: Institute of Science and Technology in Medicine, Keele University at Leopold Muller Arthritis Research Centre, RJAH Orthopaedic Hospital, Oswestry, Shropshire, United Kingdom; Faculty of Medicine and Dentistry, School of Oral and Dental Sciences, Bristol University, Bristol, United Kingdom. Electronic address: jim.middleton@bristol.ac.uk.
authors.forename: Jim
authors.initials: J
authors.lastname: Middleton
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D018000:Receptors, Peptide / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C103539:GPR15 protein, human; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide
keywords: Inflammation; Monocyte/macrophage; Neutrophils; Orphan receptor GPR15/BOB; Rheumatoid arthritis
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