Interleukin-10 attenuates renal injury after myocardial infarction in diabetes

Abstract

Acute kidney injury (AKI) is a common complication after myocardial infarction (MI) and associated with significant morbidity and mortality. AKI after MI occurs more frequently in patients with diabetes, however, the underlying mechanisms are poorly understood, and specific treatments are lacking. Using the murine MI model, we show that diabetic mice had higher expression of the kidney injury marker, neutrophil gelatinase-associated lipocalin (NGAL), 3 days after MI compared with control mice. This higher expression of NGAL was still significant after controlling for differences in myocardial infarct size between diabetic and control mice. Prior data demonstrate increased cell-free hemoglobin after MI in diabetic mice. Therefore, we investigated heme clearance components, including heme oxygenase 1 (HO-1) and CD163, in the kidneys and found that both HO-1 and CD163 were dysregulated in diabetic mice pre-MI and post-MI. Significantly higher levels of urine iron were also observed in diabetic mice compared with control mice after MI. Next, the renal protective effect of interleukin 10 (IL-10) after MI was tested in diabetic MI. IL-10 treatment demonstrated multiple protective effects after diabetic MI including reduction in acute renal inflammation, upregulation of renal heme clearance pathways, attenuation of chronic renal fibrosis, and reduction in albuminuria after diabetic MI. In vitro, IL-10 potentiated hemoglobin-induced HO-1 expression in mouse bone marrow-derived macrophages and renal proximal tubule (HK-2) cells. Furthermore, IL-10 reduced hemoglobin-induced reactive oxygen species in HK-2 cells and collagen synthesis in mouse embryonic fibroblast cells. We conclude that impaired renal heme clearance pathways in diabetes contribute to AKI after MI, and IL-10 attenuates renal injury after diabetic MI.

Macrophage is vital for C5b-9-induced cyst formation and enlargement in Pkd1 -/- mice

“…Katherine et al con rmed that primary ADPKD or NHK cells promote macrophage conversion to a distinct M2-like phenotype (16). In the present study, we revealed that RTECs were indispensable for M1-to-M2 transition of renal macrophages and that RTECs signi cantly upregulate the expression of IL-10 in the renal macrophages, which further stimulated RTEC proliferation (40). Some of the limitations of this study are as follows.…”

Identification and validation of voltage‐dependent anion channel 1‐related genes and immune cell infiltration in diabetic nephropathy

“…There is an increasing amount of evidence showing that the PI3K/AKT 55 , TGF‐β 56 , Notch 57 and Wnt pathways 58 are activated during DN development. IL‐10 polymorphism was elucidated as a protective factor for DN 59 , as it reduced acute inflammation and fibrosis in the kidneys of diabetic mice 60 . Evidence supports the activation of IL‐17A, which aggravates kidney injury in DN 61 .…”

Peripheral Inflammatory Factors and Acute Myocardial Infarction Risk: A Mendelian Randomization Study

“…It is well known that IL-10 is an important inflammatory suppressor in the body and is implicated in the development and progression of cardiovascular diseases. Several basic experiments demonstrated that IL-10 can promote myocardial repair, inhibit cardiac remodeling, and ameliorate functional impairment of other important organs after AMI [ 26 27 28 ]. Based on the findings from the present study and previous experiments, we suggested that IL-10 was likely to prevent the development of AMI; following the disease, the inflammatory factor might in turn be upregulated in a feedback manner, serving to promote repair and improve prognosis.…”