Background The biological function of histamine is mediated through four types of histamine H1∼H4 receptors. Histamine H4 receptor (H4R) has immune-modulatory and chemotaxic effects and various immune cells express H4R.
Objectives This study aimed to determine the osteoclastogenic role of H4R in rheumatoid arthritis (RA).
Methods The expression of H4R in RA synovial fluid mononuclear cells (SFMCs), synovial fibroblasts and peripheral blood mononuclear cells (PBMCs) using real-time polymerase chain reaction (PCR). After RA SFMCs and PBMCs were treated with histamine, Th17 cytokines, such as IL-17, IL-21 and IL-22, and H4R antagonist (JNJ7777120), the gene expression and protein production of H4R and RANKL were determined by real-time PCR and ELISA. Osteoclastogenesis was assessed by counting tartrate-resistant acid phosphatase–positive multinucleated cells in peripheral blood CD14+ monocytes cultured with histamine, Th17 cytokines and JNJ7777120.
Results The synovial fluid and serum concentration of histamine was higher in RA, compared with osteoarthritis and healthy controls, respectively. The expression of H4R was increased in RA PBMCs compared with healthy controls. Histamine, IL-17, IL-21 and IL-22 stimulated the expression of H4R and RANKL in PBMCs and JNJ7777120 reduced the histamine and Th17 cytokine-induced RANKL expression. Histamine and Th17 cytokines also induced the osteoclast differentiation from peripheral blood monocytes and JNJ7777120 decreased the osteoclastogenesis.
Conclusions H4R mediates RANKL expression and osteoclast differentiation induced by histamine and Th17 cytokines. The blockage of H4R could be a new therapeutic modality for prevention of bone destruction in RA.
Acknowledgement This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (2015R1D1A1A01056763).
Disclosure of Interest None declared