Polyethylenimine-coated SPIONs trigger macrophage activation through TLR-4 signaling and ROS production and modulate podosome dynamics
Abstract Polyethylenimine (PEI) is widely used as transfection agent in preclinical studies, both in vitro and in vivo. Due to their unique chemical and physical properties, SPIONs (superparamagnetic iron oxide nanoparticles) have been thoroughly studied as nanocarriers. PEI appears to activate diff...
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| Veröffentlicht in: | Biomaterials 2015-06, Vol.52, p.494-506 |
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| creator | Mulens-Arias, Vladimir Rojas, José M Pérez-Yagüe, Sonia Morales, María P Barber, Domingo F |
| description | Abstract Polyethylenimine (PEI) is widely used as transfection agent in preclinical studies, both in vitro and in vivo. Due to their unique chemical and physical properties, SPIONs (superparamagnetic iron oxide nanoparticles) have been thoroughly studied as nanocarriers. PEI appears to activate different immune cells to an inflammatory response (M1/TH 1), whereas the SPION-induced response seems to be context-dependent; the immunogenicity of the combination of these components has not been studied. Here we show that PEI-coated SPIONs (PMag) activate macrophages, as determined by measuring IL-12 secretion into culture medium and upregulation of several genes linked to the M1 phenotype. PMag-induced phosphorylation of p38 MAPK, p44/p42 MAPK and JNK, and upregulation of CD40, CD80, CD86 and I-A/I-E activation markers. PMag-induced macrophage activation depended partially on TLR4 (Toll-like receptor 4) and ROS (reactive oxygen species) signaling. Comparison of these responses with the LPS (lipopolysaccharide)-induced phenotype showed differences in gene expression profiling. PMag positively modulated podosome formation in murine macrophages, but hampered gelatin degradation by these cells. In conclusion, PMag induced an M1-like phenotype that was partially dependent on both TLR4 and ROS. These results show the adjuvant potential of PMag and suggest their use in vaccination schedules. |
| doi_str_mv | 10.1016/j.biomaterials.2015.02.068 |
| format | Article |
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Due to their unique chemical and physical properties, SPIONs (superparamagnetic iron oxide nanoparticles) have been thoroughly studied as nanocarriers. PEI appears to activate different immune cells to an inflammatory response (M1/TH 1), whereas the SPION-induced response seems to be context-dependent; the immunogenicity of the combination of these components has not been studied. Here we show that PEI-coated SPIONs (PMag) activate macrophages, as determined by measuring IL-12 secretion into culture medium and upregulation of several genes linked to the M1 phenotype. PMag-induced phosphorylation of p38 MAPK, p44/p42 MAPK and JNK, and upregulation of CD40, CD80, CD86 and I-A/I-E activation markers. PMag-induced macrophage activation depended partially on TLR4 (Toll-like receptor 4) and ROS (reactive oxygen species) signaling. Comparison of these responses with the LPS (lipopolysaccharide)-induced phenotype showed differences in gene expression profiling. PMag positively modulated podosome formation in murine macrophages, but hampered gelatin degradation by these cells. In conclusion, PMag induced an M1-like phenotype that was partially dependent on both TLR4 and ROS. These results show the adjuvant potential of PMag and suggest their use in vaccination schedules.</description><identifier>ISSN: 0142-9612</identifier><identifier>EISSN: 1878-5905</identifier><identifier>DOI: 10.1016/j.biomaterials.2015.02.068</identifier><identifier>PMID: 25818455</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Activation ; Advanced Basic Science ; Animals ; Biomedical materials ; Degradation ; Dentistry ; Enzyme-Linked Immunosorbent Assay ; Female ; Ferric Compounds - chemistry ; Genes ; Humans ; Immune response ; Immune System ; Inflammation - metabolism ; Interleukin-12 - metabolism ; Lipopolysaccharides - chemistry ; Macrophage Activation - drug effects ; Macrophages ; Macrophages - drug effects ; Macrophages - metabolism ; Mice ; Mice, Inbred C57BL ; Nanoparticle ; Nanoparticles - chemistry ; Nanostructure ; Phenotype ; Phosphorylation ; Podosomes - metabolism ; Polyetherimides ; Polyethyleneimine - chemistry ; Reactive Oxygen Species - metabolism ; Secretions ; Signal Transduction ; Surgical implants ; Toll-Like Receptor 4 - metabolism</subject><ispartof>Biomaterials, 2015-06, Vol.52, p.494-506</ispartof><rights>Elsevier Ltd</rights><rights>2015 Elsevier Ltd</rights><rights>Copyright © 2015 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c567t-1ad0284b13195b7c45a914112e711fb1927a7817345e39388c7827ccf105a6b43</citedby><cites>FETCH-LOGICAL-c567t-1ad0284b13195b7c45a914112e711fb1927a7817345e39388c7827ccf105a6b43</cites><orcidid>0000-0001-8824-5405</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0142961215001921$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25818455$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mulens-Arias, Vladimir</creatorcontrib><creatorcontrib>Rojas, José M</creatorcontrib><creatorcontrib>Pérez-Yagüe, Sonia</creatorcontrib><creatorcontrib>Morales, María P</creatorcontrib><creatorcontrib>Barber, Domingo F</creatorcontrib><title>Polyethylenimine-coated SPIONs trigger macrophage activation through TLR-4 signaling and ROS production and modulate podosome dynamics</title><title>Biomaterials</title><addtitle>Biomaterials</addtitle><description>Abstract Polyethylenimine (PEI) is widely used as transfection agent in preclinical studies, both in vitro and in vivo. Due to their unique chemical and physical properties, SPIONs (superparamagnetic iron oxide nanoparticles) have been thoroughly studied as nanocarriers. PEI appears to activate different immune cells to an inflammatory response (M1/TH 1), whereas the SPION-induced response seems to be context-dependent; the immunogenicity of the combination of these components has not been studied. Here we show that PEI-coated SPIONs (PMag) activate macrophages, as determined by measuring IL-12 secretion into culture medium and upregulation of several genes linked to the M1 phenotype. PMag-induced phosphorylation of p38 MAPK, p44/p42 MAPK and JNK, and upregulation of CD40, CD80, CD86 and I-A/I-E activation markers. PMag-induced macrophage activation depended partially on TLR4 (Toll-like receptor 4) and ROS (reactive oxygen species) signaling. Comparison of these responses with the LPS (lipopolysaccharide)-induced phenotype showed differences in gene expression profiling. PMag positively modulated podosome formation in murine macrophages, but hampered gelatin degradation by these cells. In conclusion, PMag induced an M1-like phenotype that was partially dependent on both TLR4 and ROS. These results show the adjuvant potential of PMag and suggest their use in vaccination schedules.</description><subject>Activation</subject><subject>Advanced Basic Science</subject><subject>Animals</subject><subject>Biomedical materials</subject><subject>Degradation</subject><subject>Dentistry</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Female</subject><subject>Ferric Compounds - chemistry</subject><subject>Genes</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immune System</subject><subject>Inflammation - metabolism</subject><subject>Interleukin-12 - metabolism</subject><subject>Lipopolysaccharides - chemistry</subject><subject>Macrophage Activation - drug effects</subject><subject>Macrophages</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Nanoparticle</subject><subject>Nanoparticles - chemistry</subject><subject>Nanostructure</subject><subject>Phenotype</subject><subject>Phosphorylation</subject><subject>Podosomes - metabolism</subject><subject>Polyetherimides</subject><subject>Polyethyleneimine - chemistry</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Secretions</subject><subject>Signal Transduction</subject><subject>Surgical implants</subject><subject>Toll-Like Receptor 4 - metabolism</subject><issn>0142-9612</issn><issn>1878-5905</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNks-O0zAQxiMEYsvCKyCLE5cUjx3HDgcktPxbqaKr7XK2HGeauiRxsZOV-gI8Nw5dEOLUkzXW75uxv2-y7BXQJVAo3-yXtfO9GTE408UloyCWlC1pqR5lC1BS5aKi4nG2oFCwvCqBXWTPYtzTVNOCPc0umFCgCiEW2c8b3x1x3B07HFzvBsytT50bsrm5Xn-NZAyubTGQ3tjgDzvTIjF2dPdmdH4g4y74qd2Ru9VtXpDo2sF0bmiJGRpyu96QQ_DNZH-j81Wfqi51Jwff-Oh7JM1xML2z8Xn2ZJv-gi8ezsvs26ePd1df8tX68_XV-1VuRSnHHExDmSpq4FCJWtpCmAoKAIYSYFtDxaSRCiQvBPKKK2WlYtLaLVBhyrrgl9nrU9_0sh8TxlH3LlrsOjOgn6IGKSlPPil2BsqZAqH4GWhZyqrkrOIJfXtCk50xBtzqQ3C9CUcNVM_p6r3-N109p6sp0yndJH75MGeqe2z-Sv_EmYAPJwCTh_cOg47W4WCxcQHtqBvvzpvz7r82NsXqrOm-4xHj3k9hmDWgYxLozbxn85qBSNZVDPgvSgTR2Q</recordid><startdate>20150601</startdate><enddate>20150601</enddate><creator>Mulens-Arias, Vladimir</creator><creator>Rojas, José M</creator><creator>Pérez-Yagüe, Sonia</creator><creator>Morales, María P</creator><creator>Barber, Domingo F</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7SR</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>F28</scope><scope>JG9</scope><scope>L7M</scope><orcidid>https://orcid.org/0000-0001-8824-5405</orcidid></search><sort><creationdate>20150601</creationdate><title>Polyethylenimine-coated SPIONs trigger macrophage activation through TLR-4 signaling and ROS production and modulate podosome dynamics</title><author>Mulens-Arias, Vladimir ; Rojas, José M ; Pérez-Yagüe, Sonia ; Morales, María P ; Barber, Domingo F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c567t-1ad0284b13195b7c45a914112e711fb1927a7817345e39388c7827ccf105a6b43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Activation</topic><topic>Advanced Basic Science</topic><topic>Animals</topic><topic>Biomedical materials</topic><topic>Degradation</topic><topic>Dentistry</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Female</topic><topic>Ferric Compounds - chemistry</topic><topic>Genes</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immune System</topic><topic>Inflammation - metabolism</topic><topic>Interleukin-12 - metabolism</topic><topic>Lipopolysaccharides - chemistry</topic><topic>Macrophage Activation - drug effects</topic><topic>Macrophages</topic><topic>Macrophages - drug effects</topic><topic>Macrophages - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Nanoparticle</topic><topic>Nanoparticles - chemistry</topic><topic>Nanostructure</topic><topic>Phenotype</topic><topic>Phosphorylation</topic><topic>Podosomes - metabolism</topic><topic>Polyetherimides</topic><topic>Polyethyleneimine - chemistry</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Secretions</topic><topic>Signal Transduction</topic><topic>Surgical implants</topic><topic>Toll-Like Receptor 4 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mulens-Arias, Vladimir</creatorcontrib><creatorcontrib>Rojas, José M</creatorcontrib><creatorcontrib>Pérez-Yagüe, Sonia</creatorcontrib><creatorcontrib>Morales, María P</creatorcontrib><creatorcontrib>Barber, Domingo F</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><jtitle>Biomaterials</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mulens-Arias, Vladimir</au><au>Rojas, José M</au><au>Pérez-Yagüe, Sonia</au><au>Morales, María P</au><au>Barber, Domingo F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Polyethylenimine-coated SPIONs trigger macrophage activation through TLR-4 signaling and ROS production and modulate podosome dynamics</atitle><jtitle>Biomaterials</jtitle><addtitle>Biomaterials</addtitle><date>2015-06-01</date><risdate>2015</risdate><volume>52</volume><spage>494</spage><epage>506</epage><pages>494-506</pages><issn>0142-9612</issn><eissn>1878-5905</eissn><abstract>Abstract Polyethylenimine (PEI) is widely used as transfection agent in preclinical studies, both in vitro and in vivo. Due to their unique chemical and physical properties, SPIONs (superparamagnetic iron oxide nanoparticles) have been thoroughly studied as nanocarriers. PEI appears to activate different immune cells to an inflammatory response (M1/TH 1), whereas the SPION-induced response seems to be context-dependent; the immunogenicity of the combination of these components has not been studied. Here we show that PEI-coated SPIONs (PMag) activate macrophages, as determined by measuring IL-12 secretion into culture medium and upregulation of several genes linked to the M1 phenotype. PMag-induced phosphorylation of p38 MAPK, p44/p42 MAPK and JNK, and upregulation of CD40, CD80, CD86 and I-A/I-E activation markers. PMag-induced macrophage activation depended partially on TLR4 (Toll-like receptor 4) and ROS (reactive oxygen species) signaling. Comparison of these responses with the LPS (lipopolysaccharide)-induced phenotype showed differences in gene expression profiling. PMag positively modulated podosome formation in murine macrophages, but hampered gelatin degradation by these cells. In conclusion, PMag induced an M1-like phenotype that was partially dependent on both TLR4 and ROS. These results show the adjuvant potential of PMag and suggest their use in vaccination schedules.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>25818455</pmid><doi>10.1016/j.biomaterials.2015.02.068</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-8824-5405</orcidid></addata></record> |
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| subjects | Activation Advanced Basic Science Animals Biomedical materials Degradation Dentistry Enzyme-Linked Immunosorbent Assay Female Ferric Compounds - chemistry Genes Humans Immune response Immune System Inflammation - metabolism Interleukin-12 - metabolism Lipopolysaccharides - chemistry Macrophage Activation - drug effects Macrophages Macrophages - drug effects Macrophages - metabolism Mice Mice, Inbred C57BL Nanoparticle Nanoparticles - chemistry Nanostructure Phenotype Phosphorylation Podosomes - metabolism Polyetherimides Polyethyleneimine - chemistry Reactive Oxygen Species - metabolism Secretions Signal Transduction Surgical implants Toll-Like Receptor 4 - metabolism |
| title | Polyethylenimine-coated SPIONs trigger macrophage activation through TLR-4 signaling and ROS production and modulate podosome dynamics |
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