Role of DNA repair in host immune response and inflammation

Fontes, Fabrícia Lima; Pinheiro, Daniele Maria Lopes; Oliveira, A.L. de; Oliveira, Rayssa Karla de Medeiros; Lajus, Tirzah Braz Petta; Agnez-Lima, Lucymara Fassarella

doi:10.1016/j.mrrev.2014.11.004

Cited by 35 publications

(25 citation statements)

References 209 publications

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“…Additionally, E2F1 is phosphorylated by Ataxia Telangiectasia-Mutated (ATM) and ATM- and Rad3-related (ATR) kinases and targeted to the sites of double-stranded breaks to assist the recruitment of DNA repair enzymes (Biswas and Johnson, 2012). The role of E2Fs in DNA damage repair is particularly interesting for researchers studying innate immunity, as DNA damage can serve as a signal for innate immune receptor activation and it has been demonstrated that the DNA damage repair machinery is utilized during immune responses in both plants and mammals (Fontes et al, 2015; Yan et al, 2013). …”

Section: Why Engage Cell Cycle Regulators In Immune-related Cell Death?mentioning

confidence: 99%

Cell-Cycle Regulators and Cell Death in Immunity

Zebell

Dong

2015

Cell Host & Microbe

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Summary Various cell death mechanisms are integral to host defense in both plants and mammals. Plant defense against biotrophic pathogens is associated with programmed cell death (PCD) of the infected cell. This effector-triggered PCD is partly analogous to pyroptosis, an inflammatory host cell death process that plays a crucial role in defense against microbial infections in mammals. Plant effector-triggered PCD also shares with mammalian apoptosis the involvement of cell cycle regulators as signaling components. Here we explore the similarities between these different cell death programs as they relate to host defense and their relationship to the cell-cycle.

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Section: Why Engage Cell Cycle Regulators In Immune-related Cell Death?mentioning

confidence: 99%

Cell-Cycle Regulators and Cell Death in Immunity

Zebell

Dong

2015

Cell Host & Microbe

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“…On one hand, immune activation typically includes release of reactive oxygen and reactive nitrogen species, which damage DNA (10). Damaged DNA, cytoplasmic DNA, and extracellular DNA all act as danger-associated molecular patterns (DAMPs), which trigger innate immune responses and induce pro-inflammatory cytokine production (10, 11). For example, cytoplasmic DNA is sensed by innate immune sensors STING and AIM2 (11–14).…”

Section: Introductionmentioning

confidence: 99%

“…Nucleases that prevent cytoplasmic DNA entry and accumulation, such as Dnase2a in the endosome and Trex1 in the cytoplasm, reduce inflammation (12–14). On the other hand, immune activation can be triggered by DNA repair enzymes such as the Dnase1 superfamily endonuclease apurinic/apyrimidinic endonuclease 1 (APE1) (10). Inactivation of APE1 or other DNA repair pathways reduces pro-inflammatory cytokine production (10).…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, immune activation can be triggered by DNA repair enzymes such as the Dnase1 superfamily endonuclease apurinic/apyrimidinic endonuclease 1 (APE1) (10). Inactivation of APE1 or other DNA repair pathways reduces pro-inflammatory cytokine production (10). This suggests that DNA-modifying and sensing enzymes are intimately associated with immune activation and pro-inflammatory cytokine production.…”

Section: Introductionmentioning

confidence: 99%

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Dnase1L3 Regulates Inflammasome-Dependent Cytokine Secretion

Shi

Abbott

et al. 2017

Front. Immunol.

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Pediatric-onset systemic lupus erythematosus arises in humans and mice lacking the endonuclease Dnase1L3. When Dnase1L3 is absent, DNA from circulating apoptotic bodies is not cleared, leading to anti-DNA antibody production. Compared to early anti-DNA and anti-chromatin responses, other autoantibody responses and general immune activation in Dnase1L3−/− mice are greatly delayed. We investigated the possibility that immune activation, specifically inflammasome activation, is regulated by Dnase1L3. Here, we report that Dnase1L3 inhibition blocked both NLR family, pyrin domain containing 3 (NLRP3) and NLRC4 inflammasome-mediated release of high-mobility group box 1 protein and IL-1β. In contrast to IL-1β release, Dnase1L3 inhibition only mildly impaired NLRP3-dependent pyroptosis, as measured by propidium iodide uptake or LDH release. Mechanistically, we found that Dnase1L3 was needed to promote apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) nuclear export and speck formation. Our results demonstrate that Dnase1L3 inhibition separates cytokine secretion from pyroptosis by targeting ASC. These findings suggest that Dnase1L3 is necessary for cytokine secretion following inflammasome activation.

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“…Inflammation is part of the immune response of tissues to various stimuli (Fontes et al ., 2015). The inflammatory process is associated with the activation of inflammatory cells such as macrophages, which release inflammatory mediators including nitric oxide (NO), cytokines, and chemokines (de la Fuente et al ., 2012).…”

Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory Properties of Flavone di-C-Glycosides as Active Principles of Camellia Mistletoe, Korthalsella japonica

Kim

Yun

Lim

et al. 2016

Biomolecules & Therapeutics

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The chemical components and biological activity of Camellia mistletoe, Korthalsella japonica (Loranthaceae) are relatively unknown compared to other mistletoe species. Therefore, we investigated the phytochemical properties and biological activity of this parasitic plant to provide essential preliminary scientific evidence to support and encourage its further pharmaceutical research and development. The major plant components were chromatographically isolated using high-performance liquid chromatography and their structures were elucidated using tandem mass spectrometry and nuclear magnetic resonance anlysis. Furthermore, the anti-inflammatory activity of the 70% ethanol extract of K. japonica (KJ) and its isolated components was evaluated using a nitric oxide (NO) assay and western blot analysis for inducible NO synthase (iNOS) and cyclooxygenase (COX)-2. Three flavone di-C-glycosides, lucenin-2, vicenin-2, and stellarin-2 were identified as major components of KJ, for the first time. KJ significantly inhibited NO production and reduced iNOS and COX-2 expression in lipopolysaccharide-stimulated RAW 264.7 cells at 100 μg/mL while similar activity were observed with isolated flavone C-glycosides. In conclusion, KJ has a simple secondary metabolite profiles including flavone di-C-glycosides as major components and has a strong potential for further research and development as a source of therapeutic anti-inflammatory agents.

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Role of DNA repair in host immune response and inflammation

Cited by 35 publications

References 209 publications

Cell-Cycle Regulators and Cell Death in Immunity

Cell-Cycle Regulators and Cell Death in Immunity

Dnase1L3 Regulates Inflammasome-Dependent Cytokine Secretion

Anti-Inflammatory Properties of Flavone di-C-Glycosides as Active Principles of Camellia Mistletoe, Korthalsella japonica

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