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Cited by 53Genetic and Kidney Cyst DiseasesNF-κB Signaling PathwaysImmune Response and Inflammation

The primary cilium influences interleukin-1β-induced NFκB signalling by regulating IKK activity

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Wann, A.K.T., Chapple, J.P., Knight, M.M.·2014·Cellular Signalling
DOI 10.1016/j.cellsig.2014.04.004PMC PMC4064300
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Abstract

The primary cilium is an organelle acting as a master regulator of cellular signalling. We have previously shown that disruption of primary cilia assembly, through targeting intraflagellar transport, is associated with muted nitric oxide and prostaglandin responses to the inflammatory cytokine interleukin-1β (IL-1β). Here, we show that loss of the primary cilium disrupts specific molecular signalling events in cytosolic NFκB signalling. The induction of cyclooxygenase 2 (COX2) and inducible nitrous oxide synthase (iNOS) protein is abolished. Cells unable to assemble cilia exhibit unaffected activation of IκB kinase (IKK), but delayed and reduced degradation of IκB, due to diminished phosphorylation of inhibitor of kappa B (IκB) by IKK. This results in both delayed and reduced NFκB p65 nuclear translocation and nuclear transcript binding. We also demonstrate that heat shock protein 27 (hsp27), an established regulator of IKK, is localized to the ciliary axoneme and cellular levels are dramatically disrupted with loss of the primary cilium. These results suggest that the primary cilia compartment exerts influence over NFκB signalling. We propose that the cilium is a locality for regulation of the molecular events defining NFκB signalling events, tuning signalling as appropriate.

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  • IL-1, nitric oxide and prostaglandin E2 elongate the primary cilium in articular chondrocytes via a PKA-dependent mechanism.

    “IL-1, nitric oxide and prostaglandin E2 (PGE2) elongate the primary cilium in articular chondrocytes via a PKA-dependent mechanism (A. K. T. Wann and Knight 2012; A. K. Wann et al. 2013; A. K. T. Wann et al. 2014; Mc Fie et al. 2020).”

    From Astrocyte-specific inhibition of the primary cilium suppresses C3 expression in reactive astrocyte (2024) · cites this paper as A. K. T. Wann et al. 2014

    The Introduction (page unavailable) describes primary-cilium elongation in response to IL-1β in chondrocytes. It describes nitric oxide and PGE2 as inflammatory products released in response to IL-1β, not as agents that elongate cilia. The passages do not establish a PKA-dependent mechanism for the elongation. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Primary cilium length is regulated by inflammatory signalling.

    “In addition, primary cilium length is regulated by inflammatory signalling.”

    From Astrocyte-specific inhibition of the primary cilium suppresses C3 expression in reactive astrocyte (2024) · cites this paper as A. K. T. Wann et al. 2014

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Cited by

Sorted by citations

Authors
Wann, A. K. T., Chapple, J. P., & Knight, M. M.
Affiliations
Queen Mary University of London (GB)
Corresponding author
Wann, A.K.T.
ORCID
Venue
Cellular Signalling
Publisher
Elsevier BV
Published
2014-08
Volume
26
Issue
8
Pages
1735-1742
ISSN
0898-6568 (ISSN-L)
DOI
10.1016/j.cellsig.2014.04.004
PMC
PMC4064300
OpenAlex
W2057881087
Cited by
53
References
3
Citations by year
2026: 3 · 2025: 4 · 2024: 4 · 2023: 4 · 2022: 5 · 2021: 8 · 2020: 4 · 2019: 6 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 5 · 2014: 1
FWCI
2.41
Type
journal article
Language
en
Open access
Licence
Locations
  • Cellular Signalling (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • ePrints Soton (University of Southampton) (acceptedVersion)
  • Queen Mary Research Online (Queen Mary University of London) (submittedVersion, cc-by-nc-nd)
Funders
Versus Arthritis (19830)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
primary cilia, NF-κB signaling, IL-1β, IκB kinase, IκB phosphorylation, IκB degradation, p65 nuclear translocation, cyclooxygenase-2, inducible nitric oxide synthase, HSP27, axoneme, intraflagellar transport, inflammation
MeSH terms
Animals, Cell Line, Cilia, Phosphorylation, Signal Transduction, NF-kappa B, Chondrocytes, I-kappa B Proteins, Mice, Cyclooxygenase 2, Nitric Oxide Synthase Type II, Interleukin-1beta, HSP27 Heat-Shock Proteins

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