IL-1R signalling is critical for regulation of multi-walled carbon nanotubes-induced acute lung inflammation in C57Bl/6 mice

Abstract

Exposure to certain engineered nanomaterials has been associated with pathological changes in animal models raising concerns about potential human health effects. MWCNT have been reported to activate the NLRP3 inflammasome in vitro, correlating with lung inflammation and pathology, in vivo. In this study, we investigated the role of IL-1 signalling in pulmonary inflammatory responses in WT and IL-1R−/− mice after exposure to MWCNT. The results suggest that MWCNT were effective in inducing acute pulmonary inflammation. Additionally, WT mice demonstrated significant increased airway resistance 24 h post exposure to MWCNT, which was also blocked in the IL-1R−/− mice. In contrast, by 28 days post exposure to MWCNT, the inflammatory response that was initially absent in IL-1R−/− mice was elevated in comparison to the WT mice. These data suggest that IL-1R signalling plays a crucial role in the regulation of MWCNT-induced pulmonary inflammation.

Involvement of IL-1 genes in the cellular responses to carbon nanotube exposure

“…apoptosis [13,22,34,43,60]. An indirect but crucial role for IL-1 in the pathogenicity of CNTs has been demonstrated in C57BL/6 mice lacking IL-1 receptor (IL-1R À/À ) [14]. The results demonstrated that CNT exposure induced IL-1b production within 24 h accompanied with an acute inflammatory response which was absent in IL-1R À/À mice 24 h post CNT exposure [14].…”

“…The various members, including IL-1a and IL-1b, play a role in the cellular responses induced by exposure to nanoparticles [34,43]. IL-1a, which is active in both its precursor form and mature form, and IL-1b which is encoded as a pro-IL-1b protein and then processed by caspase-1 into a mature IL-1b protein [5,16], are regulated in response to a variety of nanoparticles in vitro and in vivo [9,14,31,33,37,61,62]. Nanoparticles induce expression of IL-1a and IL-1b in lipopolysaccharide (LPS)-primed macrophages [36], of IL-1b in human monocytes [31], fibroblasts in vitro [47], and in vivo inflammasome-associated IL-1b has been implicated in the pathogenicity of carbon nanotube (CNT) nanoparticles [18,48].…”

Environmental impact of multi-wall carbon nanotubes in a novel model of exposure: systemic distribution, macrophage accumulation, and amyloid deposition

“…CNTs have been previously associated with foreign body reactions, 21,23 including migration, activation of immune cells and induction of frustrated phagocytosis, 25 and activation of the NLRP3 inflammasome, 3,[27][28][29][30]41 leading to inflammation. 60 The nanometer scale and needle shape of CNTs recall that of crocidolite asbestos fibers, 54 and CNT administration has been associated with inflammation, fibrosis, and mesothelioma.…”

“…14,[20][21][22][23] The effects of pristine (nonfunctionalized) CNTs most commonly involve immune innate reactions, including enhancement of oxidative damage, 24 fibrosis, 13,22,23 collagen-rich granuloma formation, 23 and inflammation. [25][26][27][28][29][30] When entering biological fluids, CNTs are rapidly coated by proteins, forming a biological protein corona. 31,32 In particular, the hydrophobic interactions between CNTs and proteins could also play a role in inducing proteins to form a cross-sheet, a characteristic of amyloid.…”

“…36 In this context, data concerning the ability of CNTs to induce protein aggregation and amyloid fiber formation are controversial. [37][38][39][40] The NLRP3 inflammasome, associated with immune responses to CNTs, [27][28][29][30]41 activates release of IL-18, 42 a cytokine associated with amyloid plaque formation in Alzheimer's disease, [43][44][45][46] a neurodegenerative disorder characterized by amyloid accumulation. For these reasons, we investigated the ability of CNTs to induce amyloid production and deposition in vivo, an innate defense mechanism present in most eukaryotic phyla ranging from fungi and invertebrates [47][48][49] to humans.…”