Lipopolysaccharide Adsorbed to the Bio-Corona of TiO2 Nanoparticles Powerfully Activates Selected Pro-inflammatory Transduction Pathways
It is known that the adsorption of bioactive molecules provides engineered nanoparticles (NPs) with novel biological activities. However, the biological effects of the adsorbed molecules may also be modified by the interaction with NP. Bacterial lipopolysaccharide (LPS), a powerful pro-inflammatory...
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| Format: | Article |
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Frontiers Media S.A.
2017-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00866/full |
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| author | Massimiliano G. Bianchi Manfredi Allegri Martina Chiu Anna L. Costa Magda Blosi Simona Ortelli Ovidio Bussolati Enrico Bergamaschi |
| author_facet | Massimiliano G. Bianchi Manfredi Allegri Martina Chiu Anna L. Costa Magda Blosi Simona Ortelli Ovidio Bussolati Enrico Bergamaschi |
| author_sort | Massimiliano G. Bianchi |
| collection | DOAJ |
| description | It is known that the adsorption of bioactive molecules provides engineered nanoparticles (NPs) with novel biological activities. However, the biological effects of the adsorbed molecules may also be modified by the interaction with NP. Bacterial lipopolysaccharide (LPS), a powerful pro-inflammatory compound, is a common environmental contaminant and is present in several body compartments such as the gut. We recently observed that the co-incubation of LPS with TiO2 NPs markedly potentiates its pro-inflammatory effects on murine macrophages, suggesting that, when included in a NP bio-corona, LPS activity is enhanced. To distinguish the effects of adsorbed LPS from those of the free endotoxin, a pellet fraction, denominated P25/LPS, was isolated by centrifugation from a mixture of P25 TiO2 NP (128 µg/ml) and LPS (10 ng/ml) in the presence of fetal bovine serum. Western blot analysis of the pellet eluate indicated that the P25/LPS fraction contained, besides proteins, also LPS, pointing to the presence of LPS-doped NP. The effects of adsorbed or free LPS were then compared in Raw264.7 murine macrophages. RT-PCR was used to evaluate the induction of cytokine genes, whereas active, phosphorylated isoforms of proteins involved in signaling pathways were assessed with western blot. At a nominal LPS concentration of 40 pg/ml, P25/LPS induced the expression of both NF-κB and IRF3-dependent cytokines at levels comparable with those observed with free LPS (10 ng/ml), although with different time courses. Moreover, compared to free LPS, P25/LPS caused a more sustained phosphorylation of p38 MAPK and a more prolonged induction of STAT1-dependent genes. Cytochalasin B partially inhibited the induction of Tnfa by P25/LPS, but not by free LPS, and suppressed the induction of IRF3-dependent genes by either P25/LPS or free LPS. These data suggest that, when included in the bio-corona of TiO2 NP, LPS exhibits enhanced and time-shifted pro-inflammatory effects. Thus, in assessing the hazard of NP in real life, the enhanced effects of adsorbed bioactive molecules should be taken into account. |
| first_indexed | 2024-04-12T02:27:45Z |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T02:27:45Z |
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| spelling | doaj.art-62786bffd5534b27bbc4843d6c69b87b2022-12-22T03:51:55ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-08-01810.3389/fimmu.2017.00866257192Lipopolysaccharide Adsorbed to the Bio-Corona of TiO2 Nanoparticles Powerfully Activates Selected Pro-inflammatory Transduction PathwaysMassimiliano G. Bianchi0Manfredi Allegri1Martina Chiu2Anna L. Costa3Magda Blosi4Simona Ortelli5Ovidio Bussolati6Enrico Bergamaschi7Department of Medicine and Surgery, University of Parma, Parma, ItalyDepartment of Medicine and Surgery, University of Parma, Parma, ItalyDepartment of Medicine and Surgery, University of Parma, Parma, ItalyInstitute of Science and Technology for Ceramics (CNR-ISTEC), National Research Council of Italy, Faenza, Ravenna, ItalyInstitute of Science and Technology for Ceramics (CNR-ISTEC), National Research Council of Italy, Faenza, Ravenna, ItalyInstitute of Science and Technology for Ceramics (CNR-ISTEC), National Research Council of Italy, Faenza, Ravenna, ItalyDepartment of Medicine and Surgery, University of Parma, Parma, ItalyDepartment of Public Health Science and Pediatrics, University of Turin, Turin, ItalyIt is known that the adsorption of bioactive molecules provides engineered nanoparticles (NPs) with novel biological activities. However, the biological effects of the adsorbed molecules may also be modified by the interaction with NP. Bacterial lipopolysaccharide (LPS), a powerful pro-inflammatory compound, is a common environmental contaminant and is present in several body compartments such as the gut. We recently observed that the co-incubation of LPS with TiO2 NPs markedly potentiates its pro-inflammatory effects on murine macrophages, suggesting that, when included in a NP bio-corona, LPS activity is enhanced. To distinguish the effects of adsorbed LPS from those of the free endotoxin, a pellet fraction, denominated P25/LPS, was isolated by centrifugation from a mixture of P25 TiO2 NP (128 µg/ml) and LPS (10 ng/ml) in the presence of fetal bovine serum. Western blot analysis of the pellet eluate indicated that the P25/LPS fraction contained, besides proteins, also LPS, pointing to the presence of LPS-doped NP. The effects of adsorbed or free LPS were then compared in Raw264.7 murine macrophages. RT-PCR was used to evaluate the induction of cytokine genes, whereas active, phosphorylated isoforms of proteins involved in signaling pathways were assessed with western blot. At a nominal LPS concentration of 40 pg/ml, P25/LPS induced the expression of both NF-κB and IRF3-dependent cytokines at levels comparable with those observed with free LPS (10 ng/ml), although with different time courses. Moreover, compared to free LPS, P25/LPS caused a more sustained phosphorylation of p38 MAPK and a more prolonged induction of STAT1-dependent genes. Cytochalasin B partially inhibited the induction of Tnfa by P25/LPS, but not by free LPS, and suppressed the induction of IRF3-dependent genes by either P25/LPS or free LPS. These data suggest that, when included in the bio-corona of TiO2 NP, LPS exhibits enhanced and time-shifted pro-inflammatory effects. Thus, in assessing the hazard of NP in real life, the enhanced effects of adsorbed bioactive molecules should be taken into account.http://journal.frontiersin.org/article/10.3389/fimmu.2017.00866/fulllipopolysaccharideendotoxintitanium dioxide nanoparticlesbio-coronamacrophagesinflammation |
| spellingShingle | Massimiliano G. Bianchi Manfredi Allegri Martina Chiu Anna L. Costa Magda Blosi Simona Ortelli Ovidio Bussolati Enrico Bergamaschi Lipopolysaccharide Adsorbed to the Bio-Corona of TiO2 Nanoparticles Powerfully Activates Selected Pro-inflammatory Transduction Pathways Frontiers in Immunology lipopolysaccharide endotoxin titanium dioxide nanoparticles bio-corona macrophages inflammation |
| title | Lipopolysaccharide Adsorbed to the Bio-Corona of TiO2 Nanoparticles Powerfully Activates Selected Pro-inflammatory Transduction Pathways |
| title_full | Lipopolysaccharide Adsorbed to the Bio-Corona of TiO2 Nanoparticles Powerfully Activates Selected Pro-inflammatory Transduction Pathways |
| title_fullStr | Lipopolysaccharide Adsorbed to the Bio-Corona of TiO2 Nanoparticles Powerfully Activates Selected Pro-inflammatory Transduction Pathways |
| title_full_unstemmed | Lipopolysaccharide Adsorbed to the Bio-Corona of TiO2 Nanoparticles Powerfully Activates Selected Pro-inflammatory Transduction Pathways |
| title_short | Lipopolysaccharide Adsorbed to the Bio-Corona of TiO2 Nanoparticles Powerfully Activates Selected Pro-inflammatory Transduction Pathways |
| title_sort | lipopolysaccharide adsorbed to the bio corona of tio2 nanoparticles powerfully activates selected pro inflammatory transduction pathways |
| topic | lipopolysaccharide endotoxin titanium dioxide nanoparticles bio-corona macrophages inflammation |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00866/full |
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