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

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/23874

Title:	IL-4 and IL-13 Promote Proliferation of Mammary Epithelial Cells through STAT6 and IRS-1
Authors:	Wu, WJ;Wang, SH;Wu, CC;Su, YA;Chiang, CY;Lai, CH;Wang, SH;Cheng, SL;Kuo, JY;Hsu, TC;Lin, TH;Lee, YJ
Keywords:	IL-4;IL-13;mammary glands;cell proliferation;STAT6;IRS protein
Date:	2021
Issue Date:	2022-08-05T09:44:16Z (UTC)
Publisher:	MDPI
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.
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
Relation:	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES ,2021,v22,issue 21
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

Files in This Item:

File	Description	Size	Format
index.html		0Kb	HTML	206	View/Open

Loading...