(De-) oiling inflammasomes

Abstract

Activation of inflammasome signaling can produce harmful inflammation. In this issue of Immunity, Yan et al. (2013) suggest that omega-3 fatty acids commonly found in marine oils can suppress activation of NLRP3 and NLRP1b inflammasomes.

Figure 1. Activation and inhibition of NLRP3 inflammasome signaling

Activation of the NLRP3 inflammasome is a two-signal process. “Signal 1” occurs by stimulation of toll-like receptors (TLRs) by microbial or endogenous ligands leading to NF-κB-dependent upregulation of the pro-IL-1β. “Signal 2” is provided by a wide array of NLRP3 inflammasome activators such as nigericin, anthrax lethal toxin, β-amyloid, islet amyloid polypeptide and cholesterol and monosodium irate crystals (not shown). Activated NLRP3 binds to pro-caspase-1 via the adaptor protein ASC, leading to caspase-1 cleavage of pro- IL-1β and IL-18. Yan et al. (2013) show that the mechanism for ω-3FA inhibition of NLRP3-mediated inflammation involves ω-3FAs interacting with the GPR120 and GPR40 receptors. Subsequently, the downstream scaffold protein ARRB-2 binds to GPR120 and GPR40 and the complex is internalized. There are reports that this pathway inhibits “signal 1” at the level of TAB1 and TAK1 kinases to inhibit NF-κB (Glass and Olefsky, 2012). Yan et al. (2013) also demonstrate here how “signal 2” is inhibited when ARRB-2 directly associates with NLRP3 leading to inhibition of pro-inflammatory cytokine release, and inhibition of inflammation.