Interleukin-12p35 Deletion Promotes CD4 T-Cell-Dependent Macrophage Differentiation and Enhances Angiotensin Ⅱ-Induced Cardiac Fibrosis
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.
Yulin Li Li Jie Du Congcong Zhang Yina Wu Yalei Han Wei Cui Lixin Jia Lun Cai Ji zhong Cheng Huihua
Beijing An Zhen Hospital, Capital Medical University The Key Laboratory of Remodeling-related Cardiovascular Diseases, Ministry of Education, Institute o
国内会议
北京
英文
89-91
2013-04-19（万方平台首次上网日期，不代表论文的发表时间）