Macrophage and adipocyte interaction as a source of inflammation in kidney disease.
Macrophage and adipocyte interaction as a source of inflammation in kidney disease.
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巨噬细胞和脂肪细胞相互作用是肾脏疾病炎症的根源。
DOI：
10.1038/s41598-021-82685-4
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发表时间：
2021-02-03
影响因子：
4.6
通讯作者：
Martinez Cantarin MP
中科院分区：
文献类型：
--
作者：
Martos-Rus C;Katz-Greenberg G;Lin Z;Serrano E;Whitaker-Menezes D;Domingo-Vidal M;Roche M;Ramaswamy K;Hooper DC;Falkner B;Martinez Cantarin MP
在肥胖中，脂肪组织衍生的炎症与不利的代谢后果有关。尿毒症炎症是普遍的，并有助于有害的结果。然而，脂肪组织炎症在尿毒症中的作用尚未明确。我们在体外、体内和人体样本中研究了脂肪组织对尿毒症炎症的贡献。暴露于尿毒症血清导致炎症通路的激活，包括NFκB和HIF1，炎症细胞因子/趋化因子和脂解分解代谢的上调，以及乳酸的产生。此外，与仅暴露于尿毒症血清中的脂肪细胞相比，由尿毒症血清引发的脂肪细胞与巨噬细胞共培养可导致更高的炎症细胞因子表达。BMI分层后，终末期肾病患者的脂肪组织显示巨噬细胞浸润比对照组增加。同样，患有肾脏疾病的小鼠再现了尿毒症患者的炎症状态，并且还表现出外周单核细胞增加和脂肪组织巨噬细胞（ATMS）的炎症极化。相比之下，与尿毒症野生型对照相比，尿毒症IL-6敲除小鼠脂肪组织的ATMS密度降低。ATMS密度的差异突出了IL-6在尿毒症巨噬细胞浸润中的必要作用。尿毒症促进脂肪细胞和巨噬细胞的变化，增强炎症细胞因子的产生。我们证明了尿毒症激活的巨噬细胞和脂肪组织之间的相互作用，增加了尿毒症的炎症。
In obesity, adipose tissue derived inflammation is associated with unfavorable metabolic consequences. Uremic inflammation is prevalent and contributes to detrimental outcomes. However, the contribution of adipose tissue inflammation in uremia has not been characterized. We studied the contribution of adipose tissue to uremic inflammation in-vitro, in-vivo and in human samples. Exposure to uremic serum resulted in activation of inflammatory pathways including NFκB and HIF1, upregulation of inflammatory cytokines/chemokines and catabolism with lipolysis, and lactate production. Also, co-culture of adipocytes with macrophages primed by uremic serum resulted in higher inflammatory cytokine expression than adipocytes exposed only to uremic serum. Adipose tissue of end stage renal disease subjects revealed increased macrophage infiltration compared to controls after BMI stratification. Similarly, mice with kidney disease recapitulated the inflammatory state observed in uremic patients and additionally demonstrated increased peripheral monocytes and inflammatory polarization of adipose tissue macrophages (ATMS). In contrast, adipose tissue in uremic IL-6 knock out mice showed reduced ATMS density compared to uremic wild-type controls. Differences in ATMS density highlight the necessary role of IL-6 in macrophage infiltration in uremia. Uremia promotes changes in adipocytes and macrophages enhancing production of inflammatory cytokines. We demonstrate an interaction between uremic activated macrophages and adipose tissue that augments inflammation in uremia.
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影响因子：
--
作者：
Cho, Kae Won;Morris, David L.;Lumeng, Carey N.
通讯作者：
Lumeng, Carey N.
影响因子：
19.6
作者：
Himmelfarb, J;Stenvinkel, P;Hakim, RM
通讯作者：
Hakim, RM
DOI：
10.1159/000095319
发表时间：
2006-01-01
期刊：
OBESITY AND THE KIDNEY
影响因子：
--
作者：
Kalantar-Zadeh, Kamyar;Kopple, Joel D.
通讯作者：
Kopple, Joel D.
DOI：
10.2215/cjn.03260509
发表时间：
2010-02-01
影响因子：
9.8
作者：
Merino, Ana;Portoles, Jose;Aljama, Pedro
通讯作者：
Aljama, Pedro
影响因子：
7.1
作者：
Kalantar-Zadeh, K;Block, G;Kopple, JD
通讯作者：
Kopple, JD