Dna damage in human mononuclear cells induced by bacterial endotoxin

Glukhov, I. L.; Сирота, Н. П.; Kuznetsova, Elena

doi:10.1007/s10517-008-0275-3

Cited by 17 publications

(13 citation statements)

References 12 publications

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“…LPS has been shown to induce DNA damage in several cell types [32]. To determine whether LPS-induced production of TNF-a correlated directly with DNA damage, we performed single cell gel electrophoresis (comet assays) on DNA from M1 and M2 macrophages of Fancc 2/2 and wild-type mice to quantify the DNA strand breaks.…”

Section: Tlr4-induced Overproduction Of Tnf-a and Dna Strand Breaks Imentioning

confidence: 99%

Cytokine overproduction and crosslinker hypersensitivity are unlinked in Fanconi anemia macrophages

Garbati

Hays

Rathbun

et al. 2015

Journal of Leukocyte Biology

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The Fanconi anemia proteins participate in a canonical pathway that repairs cross-linking agent-induced DNA damage. Cells with inactivated Fanconi anemia genes are universally hypersensitive to such agents. Fanconi anemia-deficient hematopoietic stem cells are also hypersensitive to inflammatory cytokines, and, as importantly, Fanconi anemia macrophages overproduce such cytokines in response to TLR4 and TLR7/8 agonists. We questioned whether TLR-induced DNA damage is the primary cause of aberrantly regulated cytokine production in Fanconi anemia macrophages by quantifying TLR agonist-induced TNF-α production, DNA strand breaks, crosslinker-induced chromosomal breakage, and Fanconi anemia core complex function in Fanconi anemia complementation group C-deficient human and murine macrophages. Although both M1 and M2 polarized Fanconi anemia cells were predictably hypersensitive to mitomycin C, only M1 macrophages overproduced TNF-α in response to TLR-activating signals. DNA damaging agents alone did not induce TNF-α production in the absence of TLR agonists in wild-type or Fanconi anemia macrophages, and mitomycin C did not enhance TLR responses in either normal or Fanconi anemia cells. TLR4 and TLR7/8 activation induced cytokine overproduction in Fanconi anemia macrophages. Also, although TLR4 activation was associated with induced double strand breaks, TLR7/8 activation was not. That DNA strand breaks and chromosome breaks are neither necessary nor sufficient to account for the overproduction of inflammatory cytokines by Fanconi anemia cells suggests that noncanonical anti-inflammatory functions of Fanconi anemia complementation group C contribute to the aberrant macrophage phenotype and suggests that suppression of macrophage/TLR hyperreactivity might prevent cytokine-induced stem cell attrition in Fanconi anemia.

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Section: Tlr4-induced Overproduction Of Tnf-a and Dna Strand Breaks Imentioning

confidence: 99%

Cytokine overproduction and crosslinker hypersensitivity are unlinked in Fanconi anemia macrophages

Garbati

Hays

Rathbun

et al. 2015

Journal of Leukocyte Biology

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“…Another intrinsic age-related state observed in numerous organisms pertains to the buildup of toxins within cells and organs [23–24]. The source of such toxins is highly variable and constitutes a significant factor in the etiology of some age-associated diseases.…”

Section: Introductionmentioning

confidence: 99%

Polyphenols and Aging

Queen¹,

Tollefsbol²

2010

CAS

165

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Age-associated changes within an individual are inherently complex and occur at multiple levels of organismal function. The overall decline in function of various tissues is known to play a key role in both aging and the complex etiology of certain age-associated diseases such as Alzheimer’s disease (AD) and cancer. Continuing research highlights the dynamic capacity of polyphenols to protect against age-associated disorders through a variety of important mechanisms. Numerous lines of evidence suggest that dietary polyphenols such as resveratrol, (−)-epigallocatechin-3-gallate (EGCG), and curcumin have the capacity to mitigate age-associated cellular damage induced via metabolic production of reactive oxygen species (ROS). However, recently acquired evidence also demonstrates a likely role for these polyphenols as anticancer agents capable of preventing formation of new vasculature in neoplastic tissues. Polyphenols have also been shown to possess other anticancer properties such as specific cell-signaling actions that may stimulate the activity of the regulatory protein SIRT1. Additionally, polyphenolic compounds have demonstrated their inhibitory effects against chronic vascular inflammation associated with atherosclerosis. These increasingly well-documented results have begun to provide a basis for considering the use of polyphenols in the development of novel therapies for certain human diseases. And while the mechanisms by which these effects occur are yet to be fully understood, it is evident that further investigation may yield a potential use for polyphenols as pharmacological interventions against specific age-associated diseases.

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“…While it is recognized that pathogens trigger an immunoinflammatory reaction into the infected sites, much less is known about the long-term effects of bacteria and/or their products on DNA damage. Mounting evidence indicates that persistent exposure to LPS, an outer membrane component of Gram-negative bacteria, causes a genotoxic effect in macrophages [ 90 ], and blood mononuclear cells [ 91 ]. Consistent with this LPS genotoxic effect, a similar response is observed in gingival fibroblasts after the exposure to this Gram-negative membrane component for 48 h in vitro [ 12 ].…”

Section: Periodontal Inflammation Creates a Permissive Environmentmentioning

confidence: 99%

Periodontal Disease and Senescent Cells: New Players for an Old Oral Health Problem?

Aquino-Martínez

Khosla

Farr

et al. 2020

IJMS

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The recent identification of senescent cells in periodontal tissues has the potential to provide new insights into the underlying mechanisms of periodontal disease etiology. DNA damage-driven senescence is perhaps one of the most underappreciated delayed consequences of persistent Gram-negative bacterial infection and inflammation. Although the host immune response rapidly protects against bacterial invasion, oxidative stress generated during inflammation can indirectly deteriorate periodontal tissues through the damage to vital cell macromolecules, including DNA. What happens to those healthy cells that reside in this harmful environment? Emerging evidence indicates that cells that survive irreparable genomic damage undergo cellular senescence, a crucial intermediate mechanism connecting DNA damage and the immune response. In this review, we hypothesize that sustained Gram-negative bacterial challenge, chronic inflammation itself, and the constant renewal of damaged tissues create a permissive environment for the abnormal accumulation of senescent cells. Based on emerging data we propose a model in which the dysfunctional presence of senescent cells may aggravate the initial immune reaction against pathogens. Further understanding of the role of senescent cells in periodontal disease pathogenesis may have clinical implications by providing more sophisticated therapeutic strategies to combat tissue destruction.

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Dna damage in human mononuclear cells induced by bacterial endotoxin

Cited by 17 publications

References 12 publications

Cytokine overproduction and crosslinker hypersensitivity are unlinked in Fanconi anemia macrophages

Cytokine overproduction and crosslinker hypersensitivity are unlinked in Fanconi anemia macrophages

Polyphenols and Aging

Periodontal Disease and Senescent Cells: New Players for an Old Oral Health Problem?

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