| Summary: | 碩士 === 中山醫學大學 === 生化微生物免疫研究所 === 106 === 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, a bias of Th2 environment prevents abortion, and at the same time, facilitates alveologenesis of mammary glands. This particular morphogenesis generates alveoli from existing ducts that requires substantial extents of cell proliferation. Using 3D cultures of primary mouse mammary epithelial cells, we have found that IL-4 and IL-13 greatly promote cell proliferation, leading to enlargement of mammary acini. This mitogenic effect is mediated by STAT6. Here we focused our studies on insulin receptor substrate-1 (IRS-1), another key signaling molecule involved in IL-4 and IL-13 signaling. Our results showed that short exposure of IL-4 or IL-13 stimulated tyrosine phosphorylation of IRS-1, but prolonged exposure enhanced IRS-1 expression with a concomitant increase in its tyrosine phosphorylation. Accordingly, pretreatment of IL-4 or IL-13 augmented insulin signaling by elevating IRS-1 expression. We also found that IL-4 and IL-13 stimulated expression of cyclin D1 and activation of matrix metalloproteinase-9 (MMP-9), which might confer the effect of IL-4 and IL-13 on cell proliferation. Taken together, our results suggest a crosstalk between IL-4/IL-13 and insulin signaling, which may help mammary gland development.
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