Pathways that Regulate ROS Scavenging Enzymes, and Their Role in Defense Against Tissue Destruction in Periodontitis

Abstract

Periodontitis, an inflammatory disease that affects the tissues surrounding the teeth, is a common disease worldwide. It is caused by a dysregulation of the host inflammatory response to bacterial infection, which leads to soft and hard tissue destruction. In particular, it is the excessive inflammation in response to bacterial plaque that leads to the release of reactive oxygen species (ROS) from neutrophils, which, then play a critical role in the destruction of periodontal tissue. Generally, ROS produced from immune cells exhibit an anti-bacterial effect and play a role in host defense and immune regulation. Excessive ROS, however, can exert cytotoxic effects, cause oxidative damage to proteins, and DNA, can interfere with cell growth and cell cycle progression, and induce apoptosis of gingival fibroblasts. Collectively, these effects enable ROS to directly induce periodontal tissue damage. Some ROS also act as intracellular signaling molecules during osteoclastogenesis, and can thus also play an indirect role in bone destruction. Cells have several protective mechanisms to manage such oxidative stress, most of which involve production of cytoprotective enzymes that scavenge ROS. These enzymes are transcriptionally regulated via NRF2, Sirtuin, and FOXO. Some reports indicate an association between periodontitis and these cytoprotective enzymes' regulatory axes, with superoxide dismutase (SOD) the most extensively investigated. In this review article, we discuss the role of oxidative stress in the tissue destruction manifest in periodontitis, and the mechanisms that protect against this oxidative stress.

Interactions between the Aggregatibacter actinomycetemcomitans secretin HofQ and host cytokines indicate a link between natural competence and interleukin-8 uptake

“…[4,5]) In this excessive inflammation neutrophils produce disproportionate amounts of reactive oxygen species (ROS) that take part in the tissue destruction (for review, see ref. [6]). In the most severe cases of periodontitis, extensive destruction of tooth-supporting tissues leads to tooth detachment [7].…”

Characterization of Filifactor alocis and its immune evasion strategies employed against human neutrophils.

“…ROS produced by neutrophils in response to bacterial plaque formation in the oral cavity plays a crucial role in antimicrobial killing (286)(287)(288)(289). However excessive uncontrolled ROS leads to a variety of detrimental host effects, including: damage to DNA and proteins, interference with cell growth and cell cycle progression and induction of apoptosis of the gingival fibroblasts (286,(290)(291)(292)(293). Additionally, ROS can impact signaling involved with osteoclastogenesis, which leads to bone destruction and periodontal disease development (286,294).…”

“…However excessive uncontrolled ROS leads to a variety of detrimental host effects, including: damage to DNA and proteins, interference with cell growth and cell cycle progression and induction of apoptosis of the gingival fibroblasts (286,(290)(291)(292)(293). Additionally, ROS can impact signaling involved with osteoclastogenesis, which leads to bone destruction and periodontal disease development (286,294). ROS can directly stimulate the degradation of extracellular matrix (ECM) through breakdown of glycosaminoglycan and matrix proteinases (286,(295)(296)(297).…”

“…ROS can directly stimulate the degradation of extracellular matrix (ECM) through breakdown of glycosaminoglycan and matrix proteinases (286,(295)(296)(297). Clinical studies have shown that markers of oxidative stress found in saliva could be used as biomarkers for periodontal disease (286,(298)(299)(300)(301).…”

“…Additionally, pre-treating the neutrophils with F. alocis and then introducing another oral microbe or multispecies community would help to determine if the oxidative killing mechanisms can be inhibited by our bacterium. From a therapeutic standpoint, it is possible that the augmentation of enzymes that protect against oxidative stress could serve beneficial for treatment of periodontitis (286).…”