Abstract | OBJECTIVE: The histamine H4 receptor (H4R) has been shown to drive inflammatory responses in models of asthma, colitis and dermatitis, and in these models it appears to affect both innate and adaptive immune responses. In this study, we used both H4R-deficient mice and a specific H4R antagonist, JNJ 28307474, to investigate the involvement of the H4R in mouse arthritis models. METHODS: H4R-deficient mice and wild-type mice administered the H4R antagonist were studied in models of collagen antibody-induced arthritis (CAIA) and collagen-induced arthritis (CIA). The impact on Th17 cells was assessed by restimulation of inguinal lymphocytes in the disease or immunisation models and with in vitro stimulation of whole blood. RESULTS: Both H4R-deficient mice and mice treated with the H4R antagonist exhibited reduced arthritis disease severity in both CAIA and CIA models. This was evident from the reduction in disease score and in joint histology. In the CIA model, treatment with the H4R antagonist reduced the number of interleukin (IL)-17 positive cells in the lymph node and the total production of IL-17. Th17 cell development in vivo was reduced in H4R-deficient mice or in mice treated with an H4R antagonist. Finally, treatment of both mouse and human blood with an H4R antagonist reduced the production of IL-17 when cells were stimulated in vitro. CONCLUSIONS:
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Authors | Jeffery M Cowden, Fuqu Yu, Homayon Banie, Mandana Farahani, Ping Ling, Steven Nguyen, Jason P Riley, Mai Zhang, Jian Zhu, Paul J Dunford, Robin L Thurmond |
Journal | Annals of the rheumatic diseases
(Ann Rheum Dis)
Vol. 73
Issue 3
Pg. 600-8
(Mar 2014)
ISSN: 1468-2060 [Electronic] England |
PMID | 24126456
(Publication Type: Journal Article)
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Chemical References |
- Hrh4 protein, mouse
- Interleukin-17
- Lipopolysaccharides
- Receptors, G-Protein-Coupled
- Receptors, Histamine
- Receptors, Histamine H4
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Topics |
- Animals
- Arthritis, Experimental
(immunology, pathology, prevention & control)
- Cells, Cultured
- Dose-Response Relationship, Drug
- Interleukin-17
(biosynthesis)
- Lipopolysaccharides
(immunology)
- Mice
- Mice, Inbred BALB C
- Mice, Inbred DBA
- Receptors, G-Protein-Coupled
(antagonists & inhibitors, deficiency, immunology)
- Receptors, Histamine
(deficiency, immunology)
- Receptors, Histamine H4
- Severity of Illness Index
- Th17 Cells
(immunology)
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