论文部分内容阅读
Objective Interleukin-12 is essential for the differentiation of na(i)ve T cells into interferon-γ-producing T cells, which regulate inflammatory responses.We investigated this process of regulating hypertension-induced cardiac fibrosis.[Methods and Results] Mice infused with angiotensin Ⅱ showed a marked increase in interleukin-12p35 expression in cardiac macrophages.The degree of cardiac fibrosis was significantly enhanced in interleukin-12p35 knockout (p35-KO) mice compared with wild-type (WT) littermates in response to angiotensin Ⅱ.Fibrotic hearts of p35-KO mice showed increased accumulation of alternatively activated (M2) macrophages and expression of M2 genes such as Arg-1 and Fizz1.Bone marrow-derived macrophages from WT or p35-KO mice did not differ in differentiation in response to angiotensin Ⅱ treatment; however, in the presence of CD4 □ T cells, macrophages from p35-KO mice differentiated into M2 macrophages and showed elevated expression of transforming growth factor-β.Moreover, CD4□ T-cell-treated p35-KO macrophages could stimulate cardiac fibroblasts to differentiate into α-smooth muscle actin-positive and collagen Ⅰ-positive myofibroblasts in 3-dimensional nanofiber gels.Neutralizing antibodies against transforming growth factor-βinhibited myofibroblast formation induced by M2 macrophages.[Conclusion] Deficiency in interleukin-12p35 regulates angiotensin H-induced cardiac fibrosis by promoting CD4□ T-cell-dependent differentiation of M2 maerophages and production of transforming growth factor-β.(ArteriosclerThrombVaseBio12012;32:1662-1674.).