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Cited by 139Genetic and Kidney Cyst DiseasesOsteoarthritis Treatment and MechanismsCystic Fibrosis Research Advances

Primary cilia elongation in response to interleukin-1 mediates the inflammatory response

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Wann, A. K. T., Knight, M. M.·2012·Cellular and Molecular Life Sciences
DOI 10.1007/s00018-012-0980-yPMC PMC3417094
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Abstract

Primary cilia are singular, cytoskeletal organelles present in the majority of mammalian cell types where they function as coordinating centres for mechanotransduction, Wnt and hedgehog signalling. The length of the primary cilium is proposed to modulate cilia function, governed in part by the activity of intraflagellar transport (IFT). In articular cartilage, primary cilia length is increased and hedgehog signaling activated in osteoarthritis (OA). Here, we examine primary cilia length with exposure to the quintessential inflammatory cytokine interleukin-1 (IL-1), which is up-regulated in OA. We then test the hypothesis that the cilium is involved in mediating the downstream inflammatory response. Primary chondrocytes treated with IL-1 exhibited a 50% increase in cilia length after 3 h exposure. IL-1-induced cilia elongation was also observed in human fibroblasts. In chondrocytes, this elongation occurred via a protein kinase A (PKA)-dependent mechanism. G-protein coupled adenylate cyclase also regulated the length of chondrocyte primary cilia but not downstream of IL-1. Chondrocytes treated with IL-1 exhibit a characteristic increase in the release of the inflammatory chemokines, nitric oxide and prostaglandin E2. However, in cells with a mutation in IFT88 whereby the cilia structure is lost, this response to IL-1 was significantly attenuated and, in the case of nitric oxide, completely abolished. Inhibition of IL-1-induced cilia elongation by PKA inhibition also attenuated the chemokine response. These results suggest that cilia assembly regulates the response to inflammatory cytokines. Therefore, the cilia proteome may provide a novel therapeutic target for the treatment of inflammatory pathologies, including OA.

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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 and Knight 2012

    The Abstract reports that IL-1 elongates primary cilia in chondrocytes through a PKA-dependent mechanism. It describes nitric oxide and PGE2 as substances released in response to IL-1, not as agents shown to elongate cilia. The cited paper therefore supports the IL-1 portion but not the claim about nitric oxide and PGE2. (LLM, conf=0.90)

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  • 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 and Knight 2012

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Authors
Wann, A. K. T., & Knight, M. M.
Affiliations
University of London (GB)
Corresponding author
Wann, A. K. T.
ORCID
Venue
Cellular and Molecular Life Sciences
Publisher
Springer Science and Business Media LLC
Published
2012-04-06
Volume
69
Issue
17
Pages
2967-2977
ISSN
  • 1420-682X (ISSN-L)
  • 1420-9071
DOI
10.1007/s00018-012-0980-y
PMC
PMC3417094
OpenAlex
W2012956265
Cited by
139
References
1
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FWCI
5.92
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Cellular and Molecular Life Sciences (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
  • Engineering and Physical Sciences Research Council (EP/E046975/1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
Keywords
primary cilia, cilia length, interleukin-1, osteoarthritis, chondrocytes, fibroblasts, protein kinase A, adenylate cyclase, G protein-coupled receptors, intraflagellar transport, IFT88, Hedgehog signaling, nitric oxide, prostaglandin E2, chemokine secretion, inflammation, mechanotransduction
MeSH terms
Animals, Cattle, Cells, Cultured, Cilia, Fibroblasts, Fluorescent Antibody Technique, Humans, Inflammation, Nitric Oxide, Dinoprostone, Signal Transduction, Cyclic AMP-Dependent Protein Kinases, Chondrocytes, Tumor Suppressor Proteins, Interleukin-1beta

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