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Media type:
E-Article
Title:
Involvement of histamine 4 receptor in the pathogenesis and progression of rheumatoid arthritis
Contributor:
Abd-Allah, Adel R. A.;
Ahmad, Sheikh Fayaz;
Alrashidi, Ibrahim;
Abdel-Hamied, Hala E.;
Zoheir, Khairy M. A.;
Ashour, Abdelkader E.;
Bakheet, Saleh A.;
Attia, Sabry M.
Published:
Oxford University Press (OUP), 2014
Published in:
International Immunology, 26 (2014) 6, Seite 325-340
Language:
English
DOI:
10.1093/intimm/dxt075
ISSN:
1460-2377;
0953-8178
Origination:
Footnote:
Description:
<jats:title>Abstract</jats:title><jats:p>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 (30mg 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 Th1 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-κB 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.</jats:p>