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Review
. 2014 Sep 29:5:352.
doi: 10.3389/fphys.2014.00352. eCollection 2014.

Reactive oxygen species at the crossroads of inflammasome and inflammation

Anantha Harijith  1 , David L Ebenezer  2 , Viswanathan Natarajan  3
Affiliations
Review

Reactive oxygen species at the crossroads of inflammasome and inflammation

Anantha Harijith et al. Front Physiol. .

Abstract

Inflammasomes form a crucial part of the innate immune system. These are multi-protein oligomer platforms that are composed of intracellular sensors which are coupled with caspase and interleukin activating systems. Nod-like receptor protein (NLRP) 3, and 6 and NLRC4 and AIM2 are the prominent members of the inflammasome family. Inflammasome activation leads to pyroptosis, a process of programmed cell death distinct from apoptosis through activation of Caspase and further downstream targets such as IL-1β and IL-18 leading to activation of inflammatory cascade. Reactive oxygen species (ROS) serves as important inflammasome activating signals. ROS activates inflammasome through mitogen-activated protein kinases (MAPK) and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2). Dysregulation of inflammasome plays a significant role in various pathological processes. Viral infections such as Dengue and Respiratory syncytial virus activate inflammasomes. Crystal compounds in silicosis and gout also activate ROS. In diabetes, inhibition of autophagy with resultant accumulation of dysfunctional mitochondria leads to enhanced ROS production activating inflammasomes. Activation of inflammasomes can be dampened by antioxidants such as SIRT-1. Inflammasome and related cascade could serve as future therapeutic targets for various pathological conditions.

Keywords: inflammasome; inflammation; reactive oxygen species.

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Figures

Figure 1
Figure 1
General schema describing the process of activation of inflammasome: initiating factors activate production of reactive oxygen species (ROS) which in turntriggers the inflammasome mediated inflammatory cascade. Oligomerization of components results in assembly of Inflammasome. This in turn activates Il-1β and Il-18 through caspase-1. NLRP3 Inflammasome promotes oxidative DNA damage. Inflammation and DNA damage culminates in pyroptosis releasing contents from the damaged cell. This in turn promotes a vicious cycle of further Inflammasome mediated pathogenic process.
Figure 2
Figure 2
Role played by Thioredoxin Interactive Protein (TXNIP) and Sirtuin in ROS induced inflammasome activation: Thioredoxin-1 (TRX1) and Thioredoxin-2 (TRX2) are part of key anti-oxidant systems in cytoplasm and mitochondria respectively. Under stress TXNIP is transferred from its usual location of nucleus to mitochondria and cytosol. TXNIP in the nucleus binds to TRX2 uncoupling it from ASK1. This results in ASK1 mediated activation of caspase-3 and promotion of ROS production by virtue of removal of inhibitory action of TRX2. Similarly TRX1 action is affected in the cytosol.Sirt1 is an NAD+-dependent class III protein deacetylase which inhibits the transactivation potential of NF-κb by deacetylation. This causes suppression of NLRP3 transcription.
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References

    1. Abais J. M., Zhang C., Xia M., Liu Q., Gehr T. W., Boini K. M., et al. (2013). NADPH oxidase-mediated triggering of inflammasome activation in mouse podocytes and glomeruli during hyperhomocysteinemia. Antioxid. Redox Signal. 18, 1537–1548 10.1089/ars.2012.4666 - DOI - PMC - PubMed
    1. Allen I. C., McElvania-TeKippe E., Wilson J. E., Lich J. D., Arthur J. C., Sullivan J. T., et al. (2013). Characterization of NLRP12 during the in vivo host immune response to Klebsiella pneumoniae and Mycobacterium tuberculosis. PLoS ONE 8:e60842 10.1371/journal.pone.0060842 - DOI - PMC - PubMed
    1. Álvarez S., Muñoz-Fernández M. Á. (2013). TNF-A may mediate inflammasome activation in the absence of bacterial infection in more than one way. PLoS ONE 8:e71477 10.1371/journal.pone.0071477 - DOI - PMC - PubMed
    1. Amaral F. A., Costa V. V., Tavares L. D., Sachs D., Coelho F. M., Fagundes C. T., et al. (2012). NLRP3 inflammasome-mediated neutrophil recruitment and hypernociception depend on leukotriene B(4) in a murine model of gout. Arthritis Rheum. 64, 474–484 10.1002/art.33355 - DOI - PubMed
    1. Andrew P. J., Mayer B. (1999). Enzymatic function of nitric oxide synthases. Cardiovasc. Res. 43, 521–531 10.1016/S0008-6363(99)00115-7 - DOI - PubMed