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AIM2 Inflammasome Activation Leads to IL-1α and TGF-β Release From Exacerbated Chronic Obstructive Pulmonary Disease-Derived Peripheral Blood Mononuclear Cells.
Front Pharmacol 2019; 10:257FP

Abstract

Chronic obstructive pulmonary disease (COPD) is now the fourth-leading cause of death worldwide and its prevalence is increasing. The progressive decline of lung function and airway remodelling are a consequence of chronic inflammatory responses. It was recently postulated the involvement of the inflammasome in COPD, although the underlying mechanism/s still need to be elucidated. Therefore, we isolated peripheral blood mononuclear cells (PBMCs) from exacerbated/unstable COPD patients. The stimulation of PBMCs with an AIM2 inflammasome activator, Poly dA:dT, led to IL-1α, but not IL-1β, release. The release of this cytokine was caspase-1- and caspase-4-dependent and correlated to higher levels of 8-OH-dG in COPD compared to non-smoker and smoker-derived PBMCs. Interestingly, AIM2-depedent IL-1α release was responsible for higher TGF-β levels, crucial mediator during pro-fibrotic processes associated to COPD progression. In conclusion, our data highlight the involvement of AIM2/caspase-1/caspase-4 in IL-1α-induced TGF-β release in unstable COPD-derived PBMCs, opening new therapeutic perspectives for unstable COPD patients.

Authors+Show Affiliations

Department of Pharmacy, University of Salerno, Fisciano, Italy. ImmunePharma s.r.l., University of Salerno, Fisciano, Italy. PhD Program in Drug Discovery and Development, Department of Pharmacy, University of Salerno, Fisciano, Italy.Department of Pharmacy, University of Salerno, Fisciano, Italy. ImmunePharma s.r.l., University of Salerno, Fisciano, Italy.Respiratory Division, Department of Respiratory Medicine, University of Naples Federico II, Naples, Italy.Respiratory Division, Department of Respiratory Medicine, University of Naples Federico II, Naples, Italy.Department of Anatomy and Pathology, Ospedale dei Colli "Monaldi-CTO," Naples, Italy.Respiratory Division, Department of Respiratory Medicine, University of Naples Federico II, Naples, Italy.Department of Pharmacy, University of Salerno, Fisciano, Italy. ImmunePharma s.r.l., University of Salerno, Fisciano, Italy.Department of Pharmacy, University of Salerno, Fisciano, Italy. ImmunePharma s.r.l., University of Salerno, Fisciano, Italy.Department of Pharmacy, University of Salerno, Fisciano, Italy. ImmunePharma s.r.l., University of Salerno, Fisciano, Italy.Department of Pharmacy, University of Salerno, Fisciano, Italy. ImmunePharma s.r.l., University of Salerno, Fisciano, Italy.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30930781

Citation

Colarusso, Chiara, et al. "AIM2 Inflammasome Activation Leads to IL-1α and TGF-β Release From Exacerbated Chronic Obstructive Pulmonary Disease-Derived Peripheral Blood Mononuclear Cells." Frontiers in Pharmacology, vol. 10, 2019, p. 257.
Colarusso C, Terlizzi M, Molino A, et al. AIM2 Inflammasome Activation Leads to IL-1α and TGF-β Release From Exacerbated Chronic Obstructive Pulmonary Disease-Derived Peripheral Blood Mononuclear Cells. Front Pharmacol. 2019;10:257.
Colarusso, C., Terlizzi, M., Molino, A., Imitazione, P., Somma, P., Rega, R., ... Sorrentino, R. (2019). AIM2 Inflammasome Activation Leads to IL-1α and TGF-β Release From Exacerbated Chronic Obstructive Pulmonary Disease-Derived Peripheral Blood Mononuclear Cells. Frontiers in Pharmacology, 10, p. 257. doi:10.3389/fphar.2019.00257.
Colarusso C, et al. AIM2 Inflammasome Activation Leads to IL-1α and TGF-β Release From Exacerbated Chronic Obstructive Pulmonary Disease-Derived Peripheral Blood Mononuclear Cells. Front Pharmacol. 2019;10:257. PubMed PMID: 30930781.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - AIM2 Inflammasome Activation Leads to IL-1α and TGF-β Release From Exacerbated Chronic Obstructive Pulmonary Disease-Derived Peripheral Blood Mononuclear Cells. AU - Colarusso,Chiara, AU - Terlizzi,Michela, AU - Molino,Antonio, AU - Imitazione,Pasquale, AU - Somma,Pasquale, AU - Rega,Roberto, AU - Saccomanno,Antonello, AU - Aquino,Rita P, AU - Pinto,Aldo, AU - Sorrentino,Rosalinda, Y1 - 2019/03/15/ PY - 2018/11/11/received PY - 2019/02/28/accepted PY - 2019/4/2/entrez PY - 2019/4/2/pubmed PY - 2019/4/2/medline KW - COPD KW - IL-1-like cytokines KW - chronic lung inflammation KW - fibrosis KW - inflammasome SP - 257 EP - 257 JF - Frontiers in pharmacology JO - Front Pharmacol VL - 10 N2 - Chronic obstructive pulmonary disease (COPD) is now the fourth-leading cause of death worldwide and its prevalence is increasing. The progressive decline of lung function and airway remodelling are a consequence of chronic inflammatory responses. It was recently postulated the involvement of the inflammasome in COPD, although the underlying mechanism/s still need to be elucidated. Therefore, we isolated peripheral blood mononuclear cells (PBMCs) from exacerbated/unstable COPD patients. The stimulation of PBMCs with an AIM2 inflammasome activator, Poly dA:dT, led to IL-1α, but not IL-1β, release. The release of this cytokine was caspase-1- and caspase-4-dependent and correlated to higher levels of 8-OH-dG in COPD compared to non-smoker and smoker-derived PBMCs. Interestingly, AIM2-depedent IL-1α release was responsible for higher TGF-β levels, crucial mediator during pro-fibrotic processes associated to COPD progression. In conclusion, our data highlight the involvement of AIM2/caspase-1/caspase-4 in IL-1α-induced TGF-β release in unstable COPD-derived PBMCs, opening new therapeutic perspectives for unstable COPD patients. SN - 1663-9812 UR - https://www.unboundmedicine.com/medline/citation/30930781/AIM2_Inflammasome_Activation_Leads_to_IL_1α_and_TGF_β_Release_From_Exacerbated_Chronic_Obstructive_Pulmonary_Disease_Derived_Peripheral_Blood_Mononuclear_Cells_ L2 - https://dx.doi.org/10.3389/fphar.2019.00257 DB - PRIME DP - Unbound Medicine ER -