Abstract
Inflammation and renal tubular injury are major features of acute kidney injury (AKI). Many cytokines and chemokines are released from injured tubular cells and acts as proinflammatory mediators. However, the role of IL-19 in the pathogenesis of AKI is not defined yet. In bilateral renal ischemia/reperfusion injury (IRI)-induced and HgCl2-induced AKI animal models, real-time quantitative (RTQ)-PCR showed that the kidneys, livers, and lungs of AKI mice expressed significantly higher IL-19 and its receptors than did sham control mice. Immunohistochemical staining showed that IL-19 and its receptors were strongly stained in the kidney, liver, and lung tissue of AKI mice. In vitro, IL-19 upregulated MCP-1, TGF-β1, and IL-19, and induced mitochondria-dependent apoptosis in murine renal tubular epithelial M-1 cells. IL-19 upregulated TNF-α and IL-10 in cultured HepG2 cells, and it increased IL-1β and TNF-α expression in cultured A549 cells. In vivo, after renal IRI or a nephrotoxic dose of HgCl2 treatment, IL-20R1-deficient mice (the deficiency blocks IL-19 signaling) showed lower levels of blood urea nitrogen (BUN) in serum and less tubular damage than did wild-type mice. Therefore, we conclude that IL-19 mediates kidney, liver, and lung tissue damage in murine AKI and that blocking IL-19 signaling may provide a potent therapeutic strategy for treating AKI.
Highlights
Acute kidney injury (AKI), called acute renal failure (ARF), affects almost 15% of patients admitted to the hospital and results in significant mortality and morbidity [1]
A number of potent mediators have been identified as generated by the injured epithelial proximal tubular cells that contribute to inflammation, including proinflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-6, IL-1b, IL-8, monocyte chemotactic protein-1 (MCP-1), transforming growth factor-b1 (TGF-b1), and regulated and normal T cell expressed and secreted (RANTES) [3]
These results suggested that IL-19 is involved in the pathogenesis of AKI in vivo
Summary
Acute kidney injury (AKI), called acute renal failure (ARF), affects almost 15% of patients admitted to the hospital and results in significant mortality and morbidity [1]. IL-10, an anti-inflammatory cytokine, decreases renal injury in mice treated with either cisplatin or ischemia [5] by inhibiting the inflammatory and apoptotic pathways. These data suggest that manipulating inflammatory cytokines may be a promising strategy for treating AKI; it is important to understand the interactions of various inflammatory cytokines and to identify the key cytokine that is the potential target of therapy, namely, the cytokine that regulates the expression of other proinflammatory cytokines, adhesion molecules, and apoptosis of tubular cells in AKI
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