title: Knockout of interleukin-17A protects against sepsis-associated acute kidney injury.
abstract: BACKGROUND
  Sepsis-associated acute kidney injury (SA-AKI) is an independent risk factor for death in patients with sepsis, but treatment for it is limited. To improve the diagnosis and treatment of SA-AKI, we must first understand its pathogenesis. Recently, interleukin (IL)-17A has been shown to be associated with the pathogenesis of acute kidney injury and sepsis, but its role in SA-AKI remains unclear.
  
  
  METHODS
  SA-AKI was induced in male C57BL/6 and IL-17A(-/-) mice using cecal ligation and puncture (CLP) operations for 24 h.
  
  
  RESULTS
  At 7 days, only seven mice survived in the wild-type septic group, but nine survived in the IL-17A(-/-) septic group, corresponding to survival rates of 25 % and 45 %, respectively. At 24 h after CLP operations, both wild-type and IL-17A(-/-) septic mice developed kidney injury. The IL-17A(-/-) septic mice exhibited decreased serum creatinine and blood urea nitrogen levels and an improved acute tubular necrosis score. The IL-17A(-/-) septic mice exhibited decreased IL-6, interferon-γ, tumor necrosis factor-α, CXCL1, CXCL2, and CXCL5 expression in kidney tissue, but increased IL-10 expression. In addition, renal neutrophil infiltration was attenuated significantly in the IL-17A(-/-) septic group. Moreover, IL-17A(-/-) septic mice showed significantly decreased apoptosis of tubular epithelial cells, including decreased TUNEL-positive tubular cell number and cleaved caspase-3 level, compared with the wild-type CLP group. Their Bax/Bcl-2 expression ratio was also increased.
  
  
  CONCLUSIONS
  Our study demonstrates that IL-17A knockout could protect against SA-AKI. We show that IL-17A plays a pathogenic role in SA-AKI by increasing the levels of proinflammatory cytokines and chemokines, and by inducing neutrophil infiltration and apoptosis of tubular epithelial cells. Accordingly, IL-17A may be a novel target in SA-AKI.
authors.affiliation: Department of Nephrology, The Affiliated Hospital of Qingdao University, Shandong, 266003, People's Republic of China.|State Key Laboratory of Kidney Diseases, Department of Nephrology, Chinese PLA General Hospital and Medical School of Chinese PLA, No.28 Fuxing Road, Beijing, 100853, People's Republic of China.
authors.forename: Cong-Juan
authors.initials: CJ
authors.lastname: Luo
authors.affiliation: Department of Nephrology, The Affiliated Hospital of Qingdao University, Shandong, 266003, People's Republic of China.|Department of Cardiology, Liaocheng People's Hospital, Shandong, 252000, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Kidney Diseases, Department of Nephrology, Chinese PLA General Hospital and Medical School of Chinese PLA, No.28 Fuxing Road, Beijing, 100853, People's Republic of China. zhangl301@hotmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, The Affiliated Hospital of Qingdao University, Shandong, 266003, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Kidney Diseases, Department of Nephrology, Chinese PLA General Hospital and Medical School of Chinese PLA, No.28 Fuxing Road, Beijing, 100853, People's Republic of China.
authors.forename: Guang-Yan
authors.initials: GY
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Kidney Diseases, Department of Nephrology, Chinese PLA General Hospital and Medical School of Chinese PLA, No.28 Fuxing Road, Beijing, 100853, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Kidney Diseases, Department of Nephrology, Chinese PLA General Hospital and Medical School of Chinese PLA, No.28 Fuxing Road, Beijing, 100853, People's Republic of China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Kidney Diseases, Department of Nephrology, Chinese PLA General Hospital and Medical School of Chinese PLA, No.28 Fuxing Road, Beijing, 100853, People's Republic of China.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Kidney Diseases, Department of Nephrology, Chinese PLA General Hospital and Medical School of Chinese PLA, No.28 Fuxing Road, Beijing, 100853, People's Republic of China. xmchen301@126.com.
authors.forename: Xiang-Mei
authors.initials: XM
authors.lastname: Chen
keywords: IL-17A knockout; Sepsis; Sepsis-associated acute kidney injury