IL-4 and IL-13 Promote Proliferation of Mammary Epithelial Cells through STAT6 and IRS-1

doi:10.3390/ijms222112008

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/23874

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题名:	IL-4 and IL-13 Promote Proliferation of Mammary Epithelial Cells through STAT6 and IRS-1
作者:	Wu, WJ;Wang, SH;Wu, CC;Su, YA;Chiang, CY;Lai, CH;Wang, SH;Cheng, SL;Kuo, JY;Hsu, TC;Lin, TH;Lee, YJ
关键词:	IL-4;IL-13;mammary glands;cell proliferation;STAT6;IRS protein
日期:	2021
上传时间:	2022-08-05T09:44:16Z (UTC)
出版者:	MDPI
摘要:	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.
URI:	http://dx.doi.org/10.3390/ijms222112008 https://www.webofscience.com/wos/woscc/full-record/WOS:000718322200001 https://ir.csmu.edu.tw:8080/handle/310902500/23874
關聯:	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES ,2021,v22,issue 21
显示于类别:	[中山醫學大學研究成果] 期刊論文

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