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Antioxid Redox Signal. 2015 Aug 10;23(5):446-59. doi: 10.1089/ars.2013.5788. Epub 2014 Feb 26.

Pharmacological Potential of NOX2 Agonists in Inflammatory Conditions.

Author information

1
1 Redoxis AB, Medicon Village , Lund, Sweden .
2
2 Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet , Stockholm, Sweden .

Abstract

SIGNIFICANCE:

New insights into the role of reactive oxygen species (ROS) show that activators of the phagocyte NADPH oxidase 2 (NOX2) complex have the potential to be therapeutic in autoimmune and inflammatory conditions. It is, however, essential to elucidate the consequence of targeting the NOX2 complex, as it might lead to different outcomes depending on disease context and specificity, dose, and timing of ROS production.

RECENT ADVANCES:

Increasing evidence is suggesting that the role of the NOX2 complex is far more complex than previously anticipated. In addition to the well-described antimicrobial response, ROS also have immune and inflammatory regulatory effects. Compounds increasing NOX2-dependent ROS production have been shown to be effective both in preventing and in treating inflammatory manifestations in animal models of autoimmune diseases. Altogether, these results suggest the possibility of activating the NOX2 complex for the treatment of autoimmune inflammatory diseases while restoring and maintaining a balanced ROS regulation.

CRITICAL ISSUES:

The complexity of the NOX system and the derived ROS is important and must be considered when designing the programs for the development of NOX2-activating drugs, as well as for validation of selected hits, to successfully identify substances effective in treating inflammatory and autoimmune conditions. In addition, it is important to consider the complex downstream immunological effects and safety for drugs that increase the production of ROS.

FUTURE DIRECTIONS:

There is a strong potential for the development of ROS-inducing drugs, targeting the NOX2 complex, which are effective and safe, for the treatment of inflammatory autoimmune disorders. In such drug development, one must carefully investigate the pharmaceutical properties, including both efficacy and safety of the drugs. In addition, the immunological pathways of this new treatment strategy need careful examination.

PMID:
24359237
DOI:
10.1089/ars.2013.5788
[Indexed for MEDLINE]

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