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IGF-1 regulates astrocytic phagocytosis and inflammation through the p110α isoform of PI3K in a sex-specific manner
dc.creator | Pinto-Benito, Daniel | es |
dc.creator | Paradela Leal, Carmen | es |
dc.creator | Ganchala, Danny | es |
dc.creator | Castro-Molina, Paula de | es |
dc.creator | Arevalo, Maria-Angeles | es |
dc.date.accessioned | 2024-04-22T16:07:53Z | |
dc.date.available | 2024-04-22T16:07:53Z | |
dc.date.issued | 2022 | |
dc.identifier.issn | 0894-1491 | es |
dc.identifier.issn | 1098-1136 | es |
dc.identifier.uri | https://hdl.handle.net/11441/156977 | |
dc.description.abstract | Insulin-like growth factor-I (IGF-I) signaling plays a key role in neuroinflammation. Here we show that IGF-1 also regulates phagocytosis of reactive astrocytes through p110α isoform of phosphatidylinositol 3-kinase (PI3K), differentially in both sexes. Systemic bacterial lipopolysaccharide (LPS)-treatment increased the expression of GFAP, a reactive astrocyte marker, in the cortex of mice in both sexes and was blocked by IGF-1 only in males. In primary astrocytes, LPS enhanced the mRNA expression of Toll-like receptors (TLR2,4) and proinflammatory factors: inducible nit- ric oxide synthase (iNOS), chemokine interferon-γ-inducible protein-10 (IP-10) and cytokines (IL-1β, IL-6, and IL-10) in male and female. Treatment with IGF-1 counteracted TLR4 but not TLR2, iNOS, and IP10 expression in both sexes and cytokines expression in males. Furthermore, reactive astrocyte phagocytosis was modulated by IGF-1 only in male astrocytes. IGF-1 was also able to increase AKT-phosphorylation only in male astrocytes. PI3K inhibitors, AG66, TGX-221, and CAL-101, with selectivity toward catalytic p110α, p110β, and p110δ isoforms respec- tively, reduced AKT-phosphorylation in males. All isoforms interact physically with IGF-1-receptor in both sexes. However, the expression of p110α is higher in males while the expression of IGF-1-receptor is similar in male and female. AG66 suppressed the IGF-1 effect on cytokine expression and counteracted the IGF- 1-produced phagocytosis decrease in male reactive astrocytes. Results suggest that sex-differences in the effect of IGF-1 on the AKT-phosphorylation could be due to a lower expression of the p110α in female and that IGF-1-effects on the inflammatory response and phagocytosis of male reactive astrocytes are mediated by p110α/PI3K subunit. | es |
dc.format | application/pdf | es |
dc.format.extent | 17 p. | es |
dc.language.iso | eng | es |
dc.publisher | Willey | es |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | IGF-1 | es |
dc.subject | Neuroinflammation | es |
dc.subject | Phagocytosis | es |
dc.subject | PI3K-isoforms | es |
dc.subject | Sex differences | es |
dc.title | IGF-1 regulates astrocytic phagocytosis and inflammation through the p110α isoform of PI3K in a sex-specific manner | es |
dc.type | info:eu-repo/semantics/article | es |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica | es |
dc.relation.publisherversion | https://onlinelibrary.wiley.com/doi/10.1002/glia.24163 | es |
dc.identifier.doi | 10.1002/glia.24163 | es |
dc.journaltitle | glia | es |
dc.publication.volumen | 70 | es |
dc.publication.issue | 6 | es |
dc.publication.initialPage | 1153 | es |
dc.publication.endPage | 1169 | es |