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Cited by 38Genetic and Kidney Cyst DiseasesCystic Fibrosis Research AdvancesCancer, Hypoxia, and Metabolism

Interleukin-1β sequesters hypoxia inducible factor 2α to the primary cilium

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Wann, Angus KT, Thompson, Clare L, Chapple, J Paul, Knight, Martin M·2013·Cilia
DOI 10.1186/2046-2530-2-17PMC PMC3886195
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Abstract

BACKGROUND: The primary cilium coordinates signalling in development, health and disease. Previously we have shown that the cilium is essential for the anabolic response to loading and the inflammatory response to interleukin-1β (IL-1β). We have also shown the primary cilium elongates in response to IL-1β exposure. Both anabolic phenotype and inflammatory pathology are proposed to be dependent on hypoxia-inducible factor 2 alpha (HIF-2α). The present study tests the hypothesis that an association exists between the primary cilium and HIFs in inflammatory signalling. RESULTS: Here we show, in articular chondrocytes, that IL-1β-induces primary cilia elongation with alterations to cilia trafficking of arl13b. This elongation is associated with a transient increase in HIF-2α expression and accumulation in the primary cilium. Prolyl hydroxylase inhibition results in primary cilia elongation also associated with accumulation of HIF-2α in the ciliary base and axoneme. This recruitment and the associated cilia elongation is not inhibited by blockade of HIFα transcription activity or rescue of basal HIF-2α expression. Hypomorphic mutation to intraflagellar transport protein IFT88 results in limited ciliogenesis. This is associated with increased HIF-2α expression and inhibited response to prolyl hydroxylase inhibition. CONCLUSIONS: These findings suggest that ciliary sequestration of HIF-2α provides negative regulation of HIF-2α expression and potentially activity. This study indicates, for the first time, that the primary cilium regulates HIF signalling during inflammation.

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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. Wann et al. 2013

    The Results report that IL-1β elongates primary cilia in bovine and human articular chondrocytes. The Background describes PGE2 and nitric oxide as products released in response to IL-1, not as agents shown to elongate cilia. The Results and Discussion identify ROCK and HDAC activity as required for IL-1β-induced elongation; they do not establish a PKA-dependent mechanism. (LLM, conf=0.89)

    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. Wann et al. 2013

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Cited by

Sorted by citations

Authors
Wann, A. K., Thompson, C. L., Chapple, J. P., & Knight, M. M.
Affiliations
Queen Mary University of London (GB)
Corresponding author
Wann, Angus KT
ORCID
Venue
Cilia
Publisher
Springer Science and Business Media LLC
Published
2013-12
Volume
2
Issue
1
Pages
17-17
ISSN
2046-2530 (ISSN-L)
DOI
10.1186/2046-2530-2-17
PMC
PMC3886195
OpenAlex
W2171346078
Cited by
38
References
6
Citations by year
2026: 3 · 2025: 4 · 2024: 6 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 5 · 2015: 1 · 2014: 3
FWCI
1.73
Type
journal article
Language
en
Open access
Licence
Locations
  • Cilia (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ePrints Soton (University of Southampton) (acceptedVersion)
  • Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
Funders
  • Wellcome Trust
  • Versus Arthritis (19830)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Keywords
primary cilia, HIF-2α, IL-1β, inflammation, articular chondrocytes, ARL13B, prolyl hydroxylase inhibition, IFT88, intraflagellar transport, ciliary trafficking

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