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.