Roles of DNA repair enzyme OGG1 in innate immunity and its significance for lung cancer

Spiros Vlahopoulos, Maria Adamaki, Nikolas Khoury, Vassilis Zoumpourlis, Istvan Boldogh

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Cytokines are pivotal mediators of the immune response, and their coordinated expression protects host tissue from excessive damage and oxidant stress. Nevertheless, the development of lung pathology, including asthma, chronic obstructive pulmonary disease, and ozone-induced lung injury, is associated with oxidant stress; as evidence, there is a significant increase in levels of the modified guanine base 7,8-dihydro-8-oxoguanine (8-oxoG) in the genome. 8-OxoG is primarily recognized by 8-oxoguanine glycosylase 1 (OGG1), which catalyzes the first step in the DNA base excision repair pathway. However, oxidant stress in the cell transiently halts enzymatic activity of substrate-bound OGG1. The stalled OGG1 facilitates DNA binding of transactivators, including NF-κB, to their cognate sites to enable expression of cytokines and chemokines, with ensuing recruitments of inflammatory cells. Hence, defective OGG1 will modulate the coordination between innate and adaptive immunity through excessive oxidant stress and cytokine dysregulation. Both oxidant stress and cytokine dysregulation constitute key elements of oncogenesis by KRAS, which is mechanistically coupled to OGG1. Thus, analysis of the mechanism by which OGG1 modulates gene expression helps discern between beneficial and detrimental effects of oxidant stress, exposes a missing functional link as a marker, and yields a novel target for lung cancer.

Original languageEnglish (US)
JournalPharmacology and Therapeutics
DOIs
StateAccepted/In press - Jan 1 2018

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DNA Repair Enzymes
Innate Immunity
Oxidants
Lung Neoplasms
Cytokines
Trans-Activators
Ozone
DNA
Guanine
Lung Injury
Adaptive Immunity
Chemokines
DNA Repair
Chronic Obstructive Pulmonary Disease
Carcinogenesis
Asthma
Genome
Pathology
Gene Expression
Lung

Keywords

  • Innate immune response
  • Kirsten-Ras
  • Lung cancer
  • Metastasis
  • OGG1
  • Reactive oxygen species

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Roles of DNA repair enzyme OGG1 in innate immunity and its significance for lung cancer. / Vlahopoulos, Spiros; Adamaki, Maria; Khoury, Nikolas; Zoumpourlis, Vassilis; Boldogh, Istvan.

In: Pharmacology and Therapeutics, 01.01.2018.

Research output: Contribution to journalArticle

Vlahopoulos, Spiros ; Adamaki, Maria ; Khoury, Nikolas ; Zoumpourlis, Vassilis ; Boldogh, Istvan. / Roles of DNA repair enzyme OGG1 in innate immunity and its significance for lung cancer. In: Pharmacology and Therapeutics. 2018.
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