The Nuclear IκB Protein IκBNS Selectively Inhibits Lipopolysaccharide-Induced IL-6 Production in Macrophages of the Colonic Lamina Propria
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Macrophages play an important role in the pathogenesis of chronic colitis. However, it remains unknown how macrophages residing in the colonic lamina propria are regulated. We characterized colonic lamina proprial CD11b-positive cells (CLPMφ). CLPMφ of wild-type mice, but not IL-10-deficient mice, displayed hyporesponsiveness to TLR stimulation in terms of cytokine production and costimulatory molecule expression. We compared CLPMφ gene expression profiles of wild-type mice with IL-10-deficient mice, and identified genes that are selectively expressed in wild-type CLPMφ. These genes included nuclear IκB proteins such as Bcl-3 and IκBNS. Because Bcl-3 has been shown to specifically inhibit LPS-induced TNF-α production, we analyzed the role of IκBNS in macrophages. Lentiviral introduction of IκBNS resulted in impaired LPS-induced IL-6 production, but not TNF-α production in the murine macrophage cell line RAW264.7. IκBNS expression led to constitutive and intense DNA binding of NF-κB p50/p50 homodimers. IκBNS was recruited to the IL-6 promoter, but not to the TNF-α promoter, together with p50. Furthermore, small interference RNA-mediated reduction in IκBNS expression in RAW264.7 cells resulted in increased LPS-induced production of IL-6, but not TNF-α. Thus, IκBNS selectively suppresses LPS-induced IL-6 production in macrophages. This study established that nuclear IκB proteins differentially regulate LPS-induced inflammatory cytokine production in macrophages.
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IκBNS inhibits IL-6 production selectively in macrophages and is induced by IL-10 and LPS.
“It has been reported that IκBNS that inhibits IL-6 production selectively in macrophages is induced by IL-10 and LPS [14].”
From Prolyl Isomerase Pin1 Protects Mice from Endotoxin Shock (2011) · cites this paper as [14]
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- Authors
- Hirotani, T., Lee, P. Y., Kuwata, H., Yamamoto, M., Matsumoto, M., Kawase, I., Akira, S., & Takeda, K.
- Affiliations
- Research Institute for Microbial Diseases, The University of Osaka (JP)
- University of Florida Health (US)
- Kyushu University (JP)
- Japan Science and Technology Agency (JP)
- The University of Osaka (JP)
- Corresponding author
- Hirotani, Tomonori
- Yamamoto, Masahiro
- Akira, Shizuo
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-03
- Volume
- 174
- Issue
- 6
- Pages
- 3650-3657
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1503222294
- Cited by
- 167
- References
- 42
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 4 · 2019: 6 · 2018: 4 · 2017: 15 · 2016: 8 · 2015: 8 · 2014: 10 · 2013: 8 · 2012: 11
- FWCI
- 3.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Keywords
- Bcl-3, interleukin-6, TNF-α, lipopolysaccharide, macrophages, colonic lamina propria, IL-10, Toll-like receptor signaling, chronic colitis, IL-6 promoter
- MeSH terms
- Animals, Base Sequence, Cell Line, Colon, DNA, Humans, Intestinal Mucosa, Lipopolysaccharides, Macrophages, Mice, Inbred C57BL, Promoter Regions, Genetic, Protein Precursors, Proteins, Recombinant Proteins, Tumor Necrosis Factor-alpha, Interleukin-6, Gene Expression, NF-kappa B, Mice, Knockout, CD11b Antigen, Intracellular Signaling Peptides and Proteins, Mice, NF-kappa B p50 Subunit, In Vitro Techniques
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