Cited by 169NF-κB Signaling PathwaysRheumatoid Arthritis Research and TherapiesNatural Compounds in Disease Treatment

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Distinct roles for the NF-κB1 (p50) and c-Rel transcription factors in inflammatory arthritis

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Campbell, Ian K., Gerondakis, Steve, O’Donnell, Kristy, Wicks, Ian P.·2000·Journal of Clinical Investigation

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Abstract

Rheumatoid arthritis (RA) is a complex disease, with contributions from systemic autoimmunity and local inflammation. Persistent synovial joint inflammation and invasive synovial pannus tissue lead to joint destruction. RA is characterized by the production of inflammatory mediators, many of which are regulated by the Rel/NF-kappaB transcription factors. Although an attractive target for therapeutic intervention in inflammatory diseases, Rel/NF-kappaB is involved in normal physiology, thus global inhibition could be harmful. An alternate approach is to identify and target the Rel/NF-kappaB subunits critical for components of disease. To assess this, mice with null mutations in c-rel or nfkb1 were used to examine directly the roles of c-Rel and p50 in models of acute and chronic inflammatory arthritis. We found c-Rel-deficient mice were resistant to collagen-induced arthritis but had a normal response in an acute, destructive arthritis model (methylated BSA/IL-1 induced arthritis) suggesting c-Rel is required for systemic but not local joint disease. In contrast, p50-deficient mice were refractory to induction of both the chronic and acute arthritis models, showing this subunit is essential for local joint inflammation and destruction. Our data suggest Rel/NF-kappaB subunits play distinct roles in the pathogenesis of inflammatory arthritis and may provide a rationale for more specific therapeutic blockade of Rel/NF-kappaB in RA.

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Authors: Campbell, I. K., Gerondakis, S., O’Donnell, K., & Wicks, I. P.
Affiliations: The Royal Melbourne Hospital (AU)
Royal Prince Alfred Hospital (AU)
Reid Health (US)
Corresponding author: Wicks, Ian P.
ORCID: Campbell, Ian K.
O’Donnell, Kristy
Wicks, Ian P.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2000-06-15
Volume: 105
Issue: 12
Pages: 1799-1806
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci8298
PMC: PMC378503
OpenAlex: W2042166751
Cited by: 168
References: 55
Citations by year: 2026: 1 · 2025: 3 · 2024: 7 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 7 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 6 · 2015: 3 · 2014: 2 · 2013: 3 · 2012: 11
FWCI: 4.89
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Arthritis Foundation
California Institute of Technology
Arthritis Foundation of Australia
Medical Research Council
National Health and Medical Research Council
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
Keywords: rheumatoid arthritis, c-Rel, collagen-induced arthritis, synovitis, joint destruction, pannus formation, arthritis pathogenesis
MeSH terms: Acute Disease, Animals, Arthritis, Experimental, Chronic Disease, Collagen, Crosses, Genetic, Inflammation, Joints, Mice, Inbred C57BL, Transcription Factors, NF-kappa B, Mice, Knockout, Proto-Oncogene Proteins c-rel, Genes, rel, Mice, NF-kappa B p50 Subunit

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Distinct roles for the NF-κB1 (p50) and c-Rel transcription factors in inflammatory arthritis

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