ArticleEuropean journal of immunology2011
Alternative activation of macrophages by IL-4 requires SHIP degradation.
Article in European journal of immunology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 105 citations in OpenAlex.
- Platelet-derived growth factor-C (PDGF-C) induces anti-apoptotic effects on macrophages through Akt and Bad phosphorylation.The Journal of biological chemistry · 2014Trial
- Mast cell-derived IL-13 as a driver of Crohn disease-associated intestinal fibrosis.Inflammatory bowel diseases · 2026Article
- SHIP blocks (MDP + LPS)-induced synergy in macrophages independent of catalytic activity.Journal of leukocyte biology · 2026Article
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- Akt inhibition enhances the antitumor efficacy of immune checkpoint blockades and radiotherapy in a syngeneic breast cancer model.Molecular therapy. Oncology · 2025Article
- Macrophage IL-4 polarization is restricted by soluble CD40 agonists and antigen-induced CD154 but not by constitutive CD154 expressed by CD4+ T cells.Journal of leukocyte biology · 2025Article
- Article
- Article
- Deficiency of INPP4A promotes M2 macrophage polarization in eosinophilic chronic rhinosinusitis with nasal polyps.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Myricetin induces M2 macrophage polarization to alleviate renal tubulointerstitial fibrosis in diabetic nephropathyWorld journal of diabetes · 2024Article
- Immunology of a unique biological structure: the Echinococcus laminated layer.Protein & cell · 2023Article
- Resveratrol regulates macrophage recruitment and M1 macrophage polarization and prevents corneal allograft rejection in rats.Frontiers in medicine · 2023Article
- Modulation of IL-4/IL-13 cytokine signaling in the context of allergic disease.The Journal of allergy and clinical immunology · 2022Review
- Sphingomyelin synthase 2 is a positive regulator of the CSF1R-STAT3 pathway in pancreatic cancer-associated macrophage.Frontiers in pharmacology · 2022Article
- GM-CSF: A Double-Edged Sword in Cancer Immunotherapy.Frontiers in immunology · 2022Review
- Benznidazole Anti-Inflammatory Effects in Murine Cardiomyocytes and Macrophages Are Mediated by Class I PI3Kδ.Frontiers in immunology · 2021Article
- Anti-Inflammatory Activity of Extracts and Pure Compounds Derived from Plants via Modulation of Signaling Pathways, Especially PI3K/AKT in Macrophages.International journal of molecular sciences · 2020Review
- Human Cytomegalovirus Mediates Unique Monocyte-to-Macrophage Differentiation through the PI3K/SHIP1/Akt Signaling Network.Viruses · 2020Article
- Human umbilical cord mesenchymal stem cells alleviate ongoing autoimmune dacryoadenitis in rabbits via polarizing macrophages into an anti-inflammatory phenotype.Experimental eye research · 2020Article
- A mechanistic integrative computational model of macrophage polarization: Implications in human pathophysiology.PLoS computational biology · 2019Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Alternatively activated macrophages are critical in host defense against parasites and are protective in inflammatory bowel disease, but contribute to pathology in asthma and solid tumors. The mechanisms underlying alternative activation of macrophages are only partially understood and little is known about their amenability to manipulation in pathophysiological conditions. Herein, we demonstrate that Src homology 2-domain-containing inositol-5'-phosphatase (SHIP)-deficient murine macrophages are more sensitive to IL-4-mediated skewing to an alternatively activated phenotype. Moreover, SHIP levels are decreased in macrophages treated with IL-4 and in murine GM-CSF-derived and tumor-associated macrophages. Loss of SHIP and induction of alternatively activated macrophage markers, Ym1 and arginase I (argI), were dependent on phosphatidylinositol 3-kinase (PI3K) activity and argI induction was dependent on the class IA PI3Kp110δ isoform. STAT6 was required to reduce SHIP protein levels, but reduced SHIP levels did not increase STAT6 phosphorylation. STAT6 transcription was inhibited by PI3K inhibitors and enhanced when SHIP was reduced using siRNA. Importantly, reducing SHIP levels enhanced, whereas SHIP overexpression or blocking SHIP degradation reduced, IL-4-induced argI activity. These findings identify SHIP and the PI3K pathway as critical regulators of alternative macrophage activation and SHIP as a target for manipulation in diseases where macrophage phenotype contributes to pathology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.