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The Interplay Between Inflammatory Signaling and Nuclear Structure and Function

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The Functional Nucleus

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Abstract

Inflammation is an adaptive response that is triggered by noxious stimuli such as infection and tissue injury. Beside immune cells representing the main source of pro-inflammatory cytokines other, mainly damaged cells, contribute to production of these cytokines. For many of the pro-inflammatory cytokines were described that their prolonged exposure activates free radicals in normal and tumor cells which results in DNA damage, changes in nuclear structure and gene expression, activation of cell cycle checkpoints and cell cycle arrest. Failure of cell proliferation may help to stop the progression of premalignant and tumor cells, but changes in gene expression in these arrested cells (tumor and normal) are often accompanied with increased production of pro-inflammatory cytokines. If these arrested cells are not eliminated from organism they pose a threat to propagation of inflammation and development of degenerative diseases, cancer and aging.

In this chapter we review the mutual interplay between DNA damage of non-immune cells and the inflammatory processes. The pro-inflammatory cytokines that are essential for the inflammatory signaling represent not only a potential consequence of the DNA damage response but these processes themselves can also induce DNA damage and trigger genome instability. The individual players involved in this interplay between cellular stress and inflammation are discussed in a detail with the intention to clearly characterize the cellular and nuclear processes and pathways that lead to release of the key pro-inflammatory cytokines. A cycle of events that subsequently affects the structural and functional features of the nucleus, including changes in the nuclear lamina and other subnuclear domains such as the promyelocytic leukemia nuclear body (PML NB) is discussed as well.

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Acknowledgments

ZH and SM were supported by Grant Agency of the Czech Republic (Project No.: 13-17658S) and Institutional Grant RVO 68378050. SH was supported by Academy of Sciences of the Czech Republic (Project No.: L200521301).

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Authors and Affiliations

  1. Department of Genome Integrity, Institute of Molecular Genetics, v.v.i., Academy of Sciences of the Czech Republic, Videnska 1083, 142 20, Prague 4, Czech Republic

    Sona Hubackova, Simona Moravcova & Zdenek Hodny

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  1. Sona Hubackova
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  2. Simona Moravcova
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  3. Zdenek Hodny
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Correspondence to Zdenek Hodny .

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  1. Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada

    David P. Bazett-Jones

  2. Dalhousie University, Halifax, Nova Scotia, Canada

    Graham Dellaire

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Hubackova, S., Moravcova, S., Hodny, Z. (2016). The Interplay Between Inflammatory Signaling and Nuclear Structure and Function. In: Bazett-Jones, D., Dellaire, G. (eds) The Functional Nucleus. Springer, Cham. https://doi.org/10.1007/978-3-319-38882-3_12

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