ArticleInternational journal of molecular sciences2021
IL-4 and IL-13 Promote Proliferation of Mammary Epithelial Cells through STAT6 and IRS-1.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- IL-4 triggers salivary duct dilatation via SHH signaling and exacerbates Sjögren's disease.Cell reports · 2026Article
- Mechanism of IL-4 mediated RPL19 promoting malignant progression in HER2 positive breast cancer.Breast cancer research : BCR · 2026Article
- STAT-independent functions of Janus kinases 1 and 2 are obligatory for the postnatal development of mammary epithelial ducts.Cell reports · 2026Article
- Th1 Cytokines Inhibit Acinar Morphogenesis and Milk Protein Expression in 3D Mammary Cultures.Biomedicines · 2025Article
- Article
- Goose Deoxycholic Acid Ameliorates Liver Injury in Laying Hens with Fatty Liver Hemorrhage Syndrome by Inhibiting the Inflammatory Response.International journal of molecular sciences · 2025Article
- Correlating milk cytokines and somatic cell counts to intramammary infections in dairy sheep.Frontiers in veterinary science · 2025Article
- IL-13 May Could Enhance the Proliferation and Affect the Differentiation of Nasal Epithelium Basal Cells Through the mTOR/p70S6K1 Pathway in Chronic Rhinosinusitis With Nasal Polyps.Mediators of inflammation · 2025Article
- Interleukin-4 prevents increased endothelial permeability by inducing pericyte survival and modulating microglial responses in diabetic retinopathy.Frontiers in endocrinology · 2025Article
- Cytokine networks and therapeutic advances in systemic lupus erythematosus.Frontiers in immunology · 2025Review
- Browning of Mammary Fat Suppresses Pubertal Mammary Gland Development of Mice via Elevation of Serum Phosphatidylcholine and Inhibition of PI3K/Akt Pathway.International journal of molecular sciences · 2023Article
- Dual Functions of T Lymphocytes in Breast Carcinoma: From Immune Protection to Orchestrating Tumor Progression and Metastasis.Cancers · 2023Review
- Mast cell ontogeny: From fetal development to life-long health and disease.Immunological reviews · 2023Review
- The Role of Insulin Receptor Substrate Proteins in Bronchopulmonary Dysplasia and Asthma: New Potential Perspectives.International journal of molecular sciences · 2022Review
- Recent Advances in the Inhibition of the IL-4 Cytokine Pathway for the Treatment of Allergen-Induced Asthma.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
T helper (Th)2 cytokines such as interleukin (IL)-4 and IL-13 control immune function by acting on leukocytes. They also regulate multiple responses in non-hematopoietic cells. During pregnancy, IL-4 and IL-13 facilitate alveologenesis of mammary glands. This particular morphogenesis generates alveoli from existing ducts and requires substantial cell proliferation. Using 3D cultures of primary mouse mammary epithelial cells, we demonstrate that IL-4 and IL-13 promote cell proliferation, leading to enlargement of mammary acini with partially filled lumens. The mitogenic effects of IL-4 and IL-13 are mediated by STAT6 as inhibition of STAT6 suppresses cell proliferation and improves lumen formation. In addition, IL-4 and IL-13 stimulate tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1). Prolonged treatment with these cytokines leads to increased IRS-1 abundance, which, in turn, amplifies IL-4- and IL-13-stimulated IRS-1 tyrosine phosphorylation. Through signaling crosstalk between IL-4/IL-13 and insulin, a hormone routinely included in mammary cultures, IRS-1 tyrosine phosphorylation is further enhanced. Lowering IRS-1 expression reduces cell proliferation, suggesting that IRS-1 is involved in IL-4- and IL-13-stimulated cell proliferation. Thus, a Th2-dominant cytokine milieu during pregnancy confers mammary gland development by promoting cell proliferation.
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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.