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Chromatin remodelling and autocrine TNFα are required for optimal interleukin-6 expression in activated human neutrophils

Author

Listed:
  • Maili Zimmermann

    (University of Verona)

  • Francisco Bianchetto Aguilera

    (University of Verona)

  • Monica Castellucci

    (University of Verona)

  • Marzia Rossato

    (University of Verona)

  • Sara Costa

    (University of Verona)

  • Claudio Lunardi

    (Section of Internal Medicine, University of Verona)

  • Renato Ostuni

    (European Institute of Oncology (IEO))

  • Giampiero Girolomoni

    (Section of Dermatology and Venereology, University of Verona)

  • Gioacchino Natoli

    (European Institute of Oncology (IEO))

  • Flavia Bazzoni

    (University of Verona)

  • Nicola Tamassia

    (University of Verona)

  • Marco A. Cassatella

    (University of Verona)

Abstract

Controversy currently exists about the ability of human neutrophils to produce IL-6. Here, we show that the chromatin organization of the IL-6 genomic locus in human neutrophils is constitutively kept in an inactive configuration. However, we also show that upon exposure to stimuli that trigger chromatin remodelling at the IL-6 locus, such as ligands for TLR8 or, less efficiently, TLR4, highly purified neutrophils express and secrete IL-6. In TLR8-activated neutrophils, but not monocytes, IL-6 expression is preceded by the induction of a latent enhancer located 14 kb upstream of the IL-6 transcriptional start site. In addition, IL-6 induction is potentiated by endogenous TNFα, which prolongs the synthesis of the IκBζ co-activator and sustains C/EBPβ recruitment and histone acetylation at IL-6 regulatory regions. Altogether, these data clarify controversial literature on the ability of human neutrophils to generate IL-6 and uncover chromatin-dependent layers of regulation of IL-6 in these cells.

Suggested Citation

  • Maili Zimmermann & Francisco Bianchetto Aguilera & Monica Castellucci & Marzia Rossato & Sara Costa & Claudio Lunardi & Renato Ostuni & Giampiero Girolomoni & Gioacchino Natoli & Flavia Bazzoni & Nico, 2015. "Chromatin remodelling and autocrine TNFα are required for optimal interleukin-6 expression in activated human neutrophils," Nature Communications, Nature, vol. 6(1), pages 1-14, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7061
    DOI: 10.1038/ncomms7061
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    Cited by:

    1. Shi Jiao & Chuanchuan Li & Fenghua Guo & Jinjin Zhang & Hui Zhang & Zhifa Cao & Wenjia Wang & Wenbo Bu & Mobin Lin & Junhong Lü & Zhaocai Zhou, 2023. "SUN1/2 controls macrophage polarization via modulating nuclear size and stiffness," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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