Epidermal Growth Factor Regulates Astrocyte Expression of the Interleukin-4 Receptor via a MAPK-Independent Pathway

Barna, Barbara P.; Mattera, Rafael; Jacobs, Barbara; Drazba, Judith A.; Estes, Marc; Prayson, Richard A.; Barnett, Gene H.

doi:10.1006/cimm.2001.1768

Cited by 8 publications

(6 citation statements)

References 29 publications

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“…In the mouse, the mitogenic effects of erbB1 activation have only been studied using EGF as a ligand (Leutz and Schachner, 1981), and in the human they have been studied on cells derived from low-grade astrocytomas, but not on normal astrocytes (Barna et al, 2001). In the absence of TGFa, astrocytes presented a low level of proliferation (Figure 5a, percentage of BrdU-immunoreactive nuclei over total nuclei numbers labelled with hematoxylin: 1 DIV, 1.570.1; 1.5 DIV, 2.770.4; 3 DIV, 9.471.9; 7 DIV, 11.271.0, mean7s.e.m., n ¼ 3).…”

Section: Resultsmentioning

confidence: 99%

Transforming growth factor alpha acts as a gliatrophin for mouse and human astrocytes

et al. 2006

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Astrocyte death has been implicated in several neuropathological diseases, but the identification of molecules susceptible of promoting astrocyte survival has been elusive. We investigated whether transforming growth factor alpha (TGFa), an erbB1/EGFR ligand, which promotes glioma progression and affects astrocyte metabolism at embryonic and adult stages, regulates astrocyte survival. Primary serum-free astrocyte cultures from postnatal mouse and fetal human cortices were used. Transforming growth factor alpha protected both species of astrocytes from staurosporine-induced apoptosis. In serum-free medium, mouse astrocytes did not survive beyond 2 months while TGFa-treated astrocytes survived up to 12 months. Transforming growth factor alpha also promoted long-term survival of human astrocytes. We additionally extended TGFa proliferative effects to human astrocytes. After 3 days of permanent application, TGFa induced a major downregulation of both erbB1 and erbB2. This downregulation did not impair the functional activation of the receptors, as ascertained by their tyrosine phosphorylation and the continuous stimulation of both ERK/MAPK and PI3K/Akt pathways up to 7 days, the longest time examined. The full cellular effects of TGFa required activation of both transduction pathways. Enhanced proliferation and survival thus define TGFa as a gliatrophin for mammalian astrocytes. These results demonstrate that in normal, non-transformed astrocytes, sustained and functional erbBs activation is achieved without bypassing ligand-induced receptors downregulation.

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Section: Resultsmentioning

confidence: 99%

Transforming growth factor alpha acts as a gliatrophin for mouse and human astrocytes

et al. 2006

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“…The IL4 receptor-alpha chain (IL4Ra) is expressed by neurons, microglia, and astrocytes 26 , 39 , 40 . However, downstream signaling differs between microglia and other CNS cell types.…”

Section: Discussionmentioning

confidence: 99%

Beige adipocytes mediate the neuroprotective and anti-inflammatory effects of subcutaneous fat in obese mice

et al. 2021

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Visceral obesity increases risk of cognitive decline in humans, but subcutaneous adiposity does not. Here, we report that beige adipocytes are indispensable for the neuroprotective and anti-inflammatory effects of subcutaneous fat. Mice lacking functional beige fat exhibit accelerated cognitive dysfunction and microglial activation with dietary obesity. Subcutaneous fat transplantation also protects against chronic obesity in wildtype mice via beige fat-dependent mechanisms. Beige adipocytes restore hippocampal synaptic plasticity following transplantation, and these effects require the anti-inflammatory cytokine interleukin-4 (IL4). After observing beige fat-mediated induction of IL4 in meningeal T-cells, we investigated the contributions of peripheral lymphocytes in donor fat. There was no sign of donor-derived lymphocyte trafficking between fat and brain, but recipient-derived lymphocytes were required for the effects of transplantation on cognition and microglial morphology. These findings indicate that beige adipocytes oppose obesity-induced cognitive impairment, with a potential role for IL4 in the relationship between beige fat and brain function.

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“…Cultured human alveolar macrophages or freshly obtained BAL cells from five animals per group of GM-CSF KO and wild-type C57Bl/6 mice were washed in PBS and lysed in a modified Nonidet P-40 lysis buffer as described previously (30). An equivalent amount of protein (25 mg) from each sample group was analyzed by 7.5% SDS-gel electrophoresis and transferred onto nitrocellulose membranes.…”

Section: Immunoblottingmentioning

confidence: 99%

ABCG1 is deficient in alveolar macrophages of GM-CSF knockout mice and patients with pulmonary alveolar proteinosis

Thomassen

Barna

Bonfield

et al. 2007

Journal of Lipid Research

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Patients with pulmonary alveolar proteinosis (PAP) display impaired surfactant clearance, foamy, lipidfilled alveolar macrophages, and increased cholesterol metabolites within the lung. Neutralizing autoantibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) are also present, resulting in virtual GM-CSF deficiency. We investigated ABCG1 and ABCA1 expression in alveolar macrophages of PAP patients and GM-CSF knockout (KO) mice, which exhibit PAP-like pulmonary pathology and increased pulmonary cholesterol. Alveolar macrophages from both sources displayed a striking similarity in transporter gene dysregulation, consisting of deficient ABCG1 accompanied by highly increased ABCA1. Peroxisome proliferator-activated receptor g (PPARg), a known regulator of both transporters, was deficient, as reported previously. In contrast, the liver X receptor a, which also upregulates both transporters, was highly increased. GM-CSF treatment increased ABCG1 expression in macrophages in vitro and in PAP patients in vivo. Overexpression of PPARg by lentivirus-PPARg transduction of primary alveolar macrophages, or activation by rosiglitazone, also increased ABCG1 expression. These results suggest that ABCG1 deficiency in PAP and GM-CSF KO alveolar macrophages is attributable to the absence of a GM-CSFmediated PPARg pathway. These findings document the existence of ABCG1 deficiency in human lung disease and highlight a critical role for ABCG1 in surfactant homeostasis.-Thomassen, M.

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Epidermal Growth Factor Regulates Astrocyte Expression of the Interleukin-4 Receptor via a MAPK-Independent Pathway

Cited by 8 publications

References 29 publications

Transforming growth factor alpha acts as a gliatrophin for mouse and human astrocytes

Transforming growth factor alpha acts as a gliatrophin for mouse and human astrocytes

Beige adipocytes mediate the neuroprotective and anti-inflammatory effects of subcutaneous fat in obese mice

ABCG1 is deficient in alveolar macrophages of GM-CSF knockout mice and patients with pulmonary alveolar proteinosis

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