| Summary: | 碩士 === 中山醫學大學 === 微生物免疫研究所 === 103 === During pregnancy, mammary glands undergo massive changes in their structures with the appearance of alveoli in the existing ducts. The luminal alveolar cells are then differentiated and acquire the ability to synthesize and secrete milk. This is delicately controlled by various hormones and growth factors. The emerging players for mammary gland development during pregnancy are T helper (Th)2 cytokines. since a Th2 bias is formed during pregnancy to prevent rejection of the fetus by the mother. We are thus interested in the role of Th2 cytokines in mammary gland development, especially interleukin-4 (IL-4). Here we found that IL-4 alone stimulates expression of the milk protein β-casein, a marker gene for differentiation, in mammary cells cultured on a reconstituted matrix of basement membrane (BM). Similar to prolactin, cell adhesion to BM is obligatory for induction of this gene. However, tyrosine phosphorylation of Stat6, the upstream signaling event of IL-4 signaling, is activated irrespective of the type of matrix, suggesting that Stat6 activity is not sufficient, and other signals elicited by cell-BM interactions are needed. For cells that are devoid of proper adhesion to BM such as culturing on tissue culture plastic, β-casein expression is weakly induced by IL-4 but can be enhanced by inhibition of the RhoA pathway. A striking feature in cells treated with IL-4 is the enlargement of mammary acinus. These cells express higher levels of proliferation cell nuclear antigen (PCNA) and incorporated higher amounts of 5-ethynyl-2’-deoxyuridine (EdU) than untreated cells, implying that IL-4 stimulates cell proliferation. IL-4 also augments the expression of insulin receptor substrate (IRS)-1 and boosts insulin signaling. Thus, IL-4 regulates not only immune functions but also cell proliferation and differentiation in mammary glands.
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