التفاصيل البيبلوغرافية
| العنوان: |
IGF‐1 regulates astrocytic phagocytosis and inflammation through the p110α isoform of PI3K in a sex‐specific manner |
| المؤلفون: |
Pinto‐Benito, Daniel, Paradela‐Leal, Carmen, Ganchala, Danny, de Castro‐Molina, Paula, Arevalo, Maria‐Angeles |
| المساهمون: |
Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable, Ministerio de Ciencia e Innovación, Federación Española de Enfermedades Raras |
| المصدر: |
Glia ; volume 70, issue 6, page 1153-1169 ; ISSN 0894-1491 1098-1136 |
| بيانات النشر: |
Wiley |
| سنة النشر: |
2022 |
| المجموعة: |
Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: |
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 nitric 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 respectively, 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. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1002/glia.24163 |
| الإتاحة: |
https://doi.org/10.1002/glia.24163Test |
| حقوق: |
http://creativecommons.org/licenses/by-nc-nd/4.0Test/ |
| رقم الانضمام: |
edsbas.AED1D165 |
| قاعدة البيانات: |
BASE |
