Redox Regulation of Inflammation: Old Elements, a New Story

Abstract

Inflammation is an essential immune response characterized by pain, swelling, redness, heat, and impaired function. A controlled acute inflammatory response is necessary to fight off infection and overcome injury. However, if the inflammatory process persists and enters into the chronic state, it can lead to local and systemic deleterious effects counterproductive to healing and instead constitutes a new pathology. Typically, inflamed tissues are associated with an elevated level of reactive species (reactive oxygen species (ROS)/reactive nitrogen species (RNS)). These ROS/RNS are generated during the respiratory burst of immune cells and are important factors in defense against invading pathogens. Additionally, reactive species are now known to trigger oxidative/nitrosative modifications of biomolecules. While most of these modifications lead to irreparable damage, some are subtle and fully reversible. The reversible modifications can initiate signaling cascades known as "redox signaling." This redox signaling tightly modulates the inflammatory response. Thus, understanding the complex role of ROS/RNS-induced redox signaling in inflammation will assist in the design of relevant therapeutic intervention strategies for inflammation-associated diseases. This review will highlight the impact of oxidative stress and redox signaling on inflammation and inflammation-associated diseases, with a focus on redox modifications of inflammation-related proteins.

Vitamin U has a protective effect on valproic acid-induced renal damage due to its anti-oxidant, anti-inflammatory, and anti-fibrotic properties

“…Most of proinflammatory cytokines such as TNF-α and IL-1β stimulate ROS generation in macrophages and neutrophils (Lei et al 2014). We have determined an increase in the levels of TNF-α, IL-1β, and MCP-1 in parallel with the increase in oxidative damage markers in the kidneys of VPAtreated rats.…”

“…The prominent microscopic findings of our study were inflammation and fibrosis. Due to the fact that redox signaling is an important regulator of inflammation and fibrosis (Eddy 2000;Lei et al 2014), we used vit U, another antioxidant molecule, to protect VPA-induced renal injury. There are many studies showing that VPA elevates the ROS levels which are considered as a life-threatening side effect of VPA therapy (Tong et al 2005;Auinger et al 2009;Tung and Winn 2011).…”

“…For instance, VPA-induced ROS generation has been observed in cases of hepatotoxicity (Tong et al 2005), neurotoxicity (Auinger et al 2009), teratogenicity (Tung and Winn 2011), and also renal toxicity (Chaudhary et al 2014). Although it is a well-known fact that inflammation is regulated by redox signaling (Lei et al 2014) and fibrosis is induced by inflammation (Eddy 2000), to date, there has been no study explaining the pathogenesis mechanism of VPA-induced renal toxicity completely.…”

Antioxidants as therapeutics in the intensive care unit: Have we ticked the redox boxes?

“…Although biochemically realistic and in certain situations valid [33], the postulation that the vicious cycle between inflammation and oxidative stress provokes per se the progression of a critical illness has seldom been experimentally confirmed in vivo and is most frequently driven by intuition. Moreover, this theory implies that the hazardous inflammation/oxidative stress feedback loop amplifies all inflammatory conditions in a similar manner.…”

Abrogating ClC-3 Inhibits LPS-induced Inflammation via Blocking the TLR4/NF-κB Pathway

“…Inflammation is an essential immune response that is characterized by pain, swelling, redness, heat, and impaired function1. It is a response to traumatic, infectious, post-ischemic, toxic, or autoimmune injury.…”