Journal
INTERNATIONAL IMMUNOLOGY
Volume 26, Issue 6, Pages 325-340Publisher
OXFORD UNIV PRESS
DOI: 10.1093/intimm/dxt075
Keywords
4-methylhistamine dihydrochloride; chemokines; collagen antibody-induced arthritis; cytokines; histamine 4 receptor; interleukin; JNJ77777120; mRNA expression; NF-kappa B p65; regulatory T cells; T-cell subsets
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Funding
- College of Pharmacy Research Center
- Deanship of Scientific Research, King Saud University, Riyadh, Saudi Arabia
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Rheumatoid arthritis (RA) is one of the major autoimmune diseases with a global prevalence. Despite significant research into this disease, no drugs with acceptable safety profiles are yet available for its treatment. We investigated the possible anti-arthritic effects of the 4-methylhistamine (4-MeH) histamine 4 receptor (H4R) agonist and the JNJ77777120 (JNJ) H4R antagonist to explore the role of H4R in a mouse model of collagen antibody-induced arthritis (CAIA). Arthritis was induced via intravenous (tail vein) injection of Balb/c mice with a 5-clone cocktail of mAbs against collagen type II, followed by LPS, and the effects of treatment with 4-MeH or JNJ (30 mg kg(-1), i.p, twice daily) for 7 days (prophylactic or therapeutic regimens) were assessed. The results revealed increased paw edema, arthritic scores, joint histological inflammatory damage and matrix metalloproteinase-3 levels and high levels of T(h)1 pro-inflammatory cytokine mRNA and serum proteins in CAIA mice or following H4R activation via 4-MeH. Additionally, 4-MeH efficiently increased expression levels of NF-kappa B p65. JNJ-treated mice showed a substantial reduction in all the previously mentioned effects, with a similar trend being observed under prophylactic and therapeutic treatment regimens. The results of the present work indicate that JNJ exhibits significant anti-inflammatory and anti-arthritic activities, demonstrating the clear involvement of H4R antagonism in the pathogenesis and progression of RA.
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