Nanoparticles activate the NLR pyrin domain containing 3 (Nlrp3) inflammasome and cause pulmonary inflammation through release of IL-1α and IL-1β.
Nanoparticles are increasingly used in various fields, including biomedicine and electronics. One application utilizes the opacifying effect of nano-TiO(2), which is frequently used as pigment in cosmetics. Although TiO(2) is believed to be biologically inert, an emerging literature reports increased incidence of respiratory diseases in people exposed to TiO(2). Here, we show that nano-TiO(2) and nano-SiO(2), but not nano-ZnO, activate the NLR pyrin domain containing 3 (Nlrp3) inflammasome, leading to IL-1β release and in addition, induce the regulated release of IL-1α. Unlike other particulate Nlrp3 agonists, nano-TiO(2)-dependent-Nlrp3 activity does not require cytoskeleton-dependent phagocytosis and induces IL-1α/β secretion in nonphagocytic keratinocytes. Inhalation of nano-TiO(2) provokes lung inflammation which is strongly suppressed in IL-1R- and IL-1α-deficient mice. Thus, the inflammation caused by nano-TiO(2) in vivo is largely caused by the biological effect of IL-1α. The current use of nano-TiO(2) may present a health hazard due to its capacity to induce IL-1R signaling, a situation reminiscent of inflammation provoked by asbestos exposure.
Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland.
Amir S
AS
Yazdi
Greta
G
Guarda
Nicolas
N
Riteau
Stefan K
SK
Drexler
Aubry
A
Tardivel
Isabelle
I
Couillin
Jürg
J
Tschopp
D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D058847:Inflammasomes / Q000187:drug effects / Q000378:metabolism*; D001239:Inhalation; D053582:Interleukin-1alpha / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D053758:Nanoparticles / Q000633:toxicity*; D011014:Pneumonia / Q000209:etiology*; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D012822:Silicon Dioxide / Q000633:toxicity; D014025:Titanium / Q000633:toxicity; D015034:Zinc Oxide
D002352:Carrier Proteins; D058847:Inflammasomes; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D017472:Receptors, Interleukin-1; C009495:titanium dioxide; D012822:Silicon Dioxide; D014025:Titanium; D015034:Zinc Oxide