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Inflammatory Cytokines Contribute to Asbestos-Induced Injury of Mesothelial Cells
Milena Marques Pagliarelli Acencio1, Barbara Soares2, Evaldo Marchi2,3
1Pleura Laboratory, Pulmonary Division - Heart Institute (InCor), University of São Paulo Medical School, Rua Dr. Eneas Carvalho Aguiar 44, 10 andar, Cerqueira Cesar, São Paulo, 05403-000, Brazil. milena.acencio@incor.usp.br.
Background:
Several diseases have been related to asbestos exposure, including the pleural tumor mesothelioma. The mechanism of pleural injury by asbestos fibers is not yet fully understood. The inflammatory response with release of mediators leading to a dysregulation of apoptosis may play a pivotal role in the pathophysiology of asbestos-induced pleural disease.
Objective:
To determine whether pro-inflammatory cytokines produced by asbestos-exposed pleural mesothelial cells modify the injury induced by the asbestos.
Methods:
Mouse pleural mesothelial cells (PMC) were exposed to crocidolite or chrysotile asbestos fibers (3.0 μg/cm(2)) for 4, 24, or 48 h and assessed for viability, necrosis and apoptosis, and the production of cytokines IL-1β, IL-6 and macrophage inflammatory protein-2 (MIP-2). Cells exposed to fibers were also treated with antibodies anti-IL-1β, anti-IL-6, anti- IL-1β+anti-IL-6 or anti-MIP-2 or their irrelevant isotypes, and assessed for apoptosis and necrosis. Non-exposed cells and cells treated with wollastonite, an inert particle, were used as controls.
Results:
Mesothelial cells exposed to either crocidolite or chrysotile underwent both apoptosis and necrosis and released cytokines IL-1β, IL-6 and MIP-2. In the crocidolite group, apoptosis and the levels of all cytokines were higher than in the chrysotile group, at comparable concentrations. Neutralization of IL-1β andIL-6, but not MIP-2, inhibited apoptosis and necrosis, especially in the cells exposed to crocidolite fibers.
Conclusions:
Both crocidolite and chrysotile asbestos fibers induced apoptosis and produced an acute inflammatory response characterized by elevated levels of IL-1β, IL-6 and MIP-2 in cultured mouse PMC. IL-1β and IL-6, but not MIP-2, were shown to contribute to asbestos-induced injury, especially in the crocidolite group.
Insights
Asbestos fibers cause pleural injury through inflammation and cell death. Interleukin-1 beta (IL-1β) and IL-6 mediate this asbestos-induced damage, particularly from crocidolite fibers.
Area of Science:
- Cell Biology
- Toxicology
- Immunology
Background:
- Asbestos exposure is linked to diseases like mesothelioma.
- The precise mechanisms of asbestos-induced pleural injury remain unclear.
- Inflammatory responses and apoptosis dysregulation are implicated in asbestos-related pleural disease.
Purpose of the Study:
- To investigate if pro-inflammatory cytokines from asbestos-exposed pleural mesothelial cells (PMC) influence asbestos-induced injury.
- To understand the role of specific cytokines in asbestos-mediated cellular damage.
Main Methods:
- Mouse PMC were exposed to crocidolite or chrysotile asbestos fibers.
- Assessed cell viability, necrosis, apoptosis, and cytokine production (IL-1β, IL-6, MIP-2).
- Neutralized specific cytokines (IL-1β, IL-6, MIP-2) to evaluate their impact on apoptosis and necrosis.
Main Results:
- Asbestos exposure induced apoptosis and necrosis in PMC, with higher levels in the crocidolite group.
- Elevated levels of IL-1β, IL-6, and MIP-2 were observed after asbestos exposure.
- Neutralizing IL-1β and IL-6, but not MIP-2, reduced asbestos-induced apoptosis and necrosis, especially with crocidolite.
Conclusions:
- Both crocidolite and chrysotile fibers trigger apoptosis and an acute inflammatory response in PMC.
- IL-1β and IL-6 play a significant role in asbestos-induced pleural injury, more so with crocidolite exposure.
- MIP-2 does not appear to contribute to the observed asbestos-induced cellular damage.
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