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Nat Commun. 2015 Jan 23;6:6061. doi: 10.1038/ncomms7061.

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

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Department of Pathology and Diagnostics, Division of General Pathology, University of Verona, 37134 Verona, Italy.
Department of Medicine, Section of Internal Medicine, University of Verona, 37134 Verona, Italy.
Department of Experimental Oncology, European Institute of Oncology (IEO), I-20139 Milan, Italy.
Department of Medicine, Section of Dermatology and Venereology, University of Verona, 37126 Verona, Italy.


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.

[Indexed for MEDLINE]

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