- Title
- Activation of the absent in melanoma 2 inflammasome in peripheral blood mononuclear cells from idiopathic pulmonary fibrosis patients leads to the release of pro-fibrotic mediators
- Creator
- Terlizzi, Michela; Molino, Antonio; Colarusso, Chiara; Donovan, Chantal; Imitazione, Pasquale; Somma, Pasquale; Aquino, Rita P.; Hansbro, Philip M.; Pinto, Aldo; Sorrentino, Rosalinda
- Relation
- Frontiers in Immunology Vol. 9, no. 670
- Publisher Link
- http://dx.doi.org/10.3389/fimmu.2018.00670
- Publisher
- Frontiers Research Foundation
- Resource Type
- journal article
- Date
- 2018
- Description
- Idiopathic pulmonary fibrosis (IPF) is a chronic fibro-proliferative disease characterized by poor prognosis, with a mean survival of ~2–3 years after definite diagnosis. The cause of IPF is still unknown but it is a heterogeneous condition in which the aberrant deposition of extracellular matrix leads to extensive lung remodeling. This remodeling is a consequence of inflammatory responses, but the mechanisms involved are poorly understood. In this study, we first analyzed a bleomycin-induced mouse model, which showed that higher expression of IL-1β, but not IL-18, was correlated to pulmonary cell infiltration and fibrosis. Then, we found that peripheral blood mononuclear cells (PBMCs) from IPF patients released IL-1α and IL-18 in a NLRP3- and calpain-independent manner after LPS ± ATP stimulation. Instead, the activation of the absent in melanoma 2 (AIM2) inflammasome induced the release of IL-1α in a caspase-1-/caspase-8-independent manner; whereas IL-18 release was caspase-1 dependent. These effects correlated with the release of the pro-fibrotic TGF-β, which was induced by AIM2 activation in a caspase-1- and TLR4-independent manner, but dependent on IL-1α. In this context, the activation of AIM2 induced the release of caspase-4 from IPF-derived PBMCs, which correlated with the mRNA levels of this caspase that was higher in IPF than in healthy PBMCs. In conclusion, our findings identify a novel molecular mechanism whereby the activation of AIM2 could lead to the activation of the non-canonical inflammasome (caspase-4 dependent) that induces the release of IL-1α responsible for the release of TGF-β from PBMCs of IPF patients.
- Subject
- idiopathic pulmonary fibrosis; absent in melanoma 2 inflammasome; IL-1α; IL-18; caspase-4
- Identifier
- http://hdl.handle.net/1959.13/1384218
- Identifier
- uon:32030
- Identifier
- ISSN:1664-3224
- Rights
- © 2018 Terlizzi, Molino, Colarusso, Donovan, Imitazione, Somma, Aquino, Hansbro, Pinto and Sorrentino. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
- Language
- eng
- Full Text
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