【摘 要】
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Objective Interleukin12 is essential for the differentiation of naive T cells into interferonγ-producing T cells,which regulate inflammatory responses.We investigated this process of regulating hypert
【机 构】
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Beijing An Zhen Hospital, Capital Medical University
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Objective Interleukin12 is essential for the differentiation of naive T cells into interferonγ-producing T cells,which regulate inflammatory responses.We investigated this process of regulating hypertensioninduced cardiac fibrosis.Methods and Results Mice infused with angiotensin Ⅱ showed a marked increase in interleukin12p35 expression in cardiac macrophages.The degree of cardiac fibrosis was significantly enhanced in interleukin12p35 knockout (p35KO) mice compared with wildtype (WT)littermates in response to angiotensin Ⅱ.Fibrotic hearts of p35KO mice showed increased accumulation of alternatively activated (M2)macrophages and expression of M2 genes such as Arg1 and Fizzl.Bone marrow-derived macrophages from WT or p35KO mice did not differ in differentiation in response to angiotensin I1 treatment; however,in the presence ofCD4 1 T cells,macrophages from p35KO mice differentiated into M2 macrophages and showed elevated expression of transforming growth factorβ.Moreover.CD4 1 Tcell-treated p35KO macrophages could stimulate cardiac fibroblasts to differentiate into α smooth muscle actin-positive and collagen 1-positive myofibroblasts in 3dimensional nanofiber gels.Neutralizing antibodies against transforming growth factor β inhibited myofibroblast formation induced by M2 macrophages.
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