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The Effect of Autophagy on Inflammation Cytokines in Renal Ischemia/Reperfusion Injury

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Abstract

Acute kidney injury (AKI) is characterized by a rapid loss of kidney function and an antigen-independent inflammatory process that causes tissue damage, which was one of the main manifestations of kidney ischemia/reperfusion (I/R). Recent studies have demonstrated autophagy participated in the pathological process of acute kidney injury. In this study, we discuss how autophagy regulated inflammation response in the kidney I/R. AKI was performed by renal I/R. Autophagy activator rapamycin (Rap) and inhibitor 3-methyladenine (MA) were used to investigate the role of autophagy on kidney function and inflammation response. After the experiment, kidney tissues were obtained for the detection of autophagy-related protein microtubule-associated protein light chain 3(LC3)II, Beclin1, and Rab7 and lysosome-associated membrane protein type (LAMP)2 protein by reverse transcription-polymerase chain reaction (PT-PCR) and Western blotting, and histopathology and tissue injury scores also. The blood was harvested to measure kidney function (creatinine (Cr) and blood urea nitrogen (BUN) levels) after I/R. Cytokines TNF-α, IL-6, HMGB1, and IL-10 were measured after I/R. I/R induced the expression of LC3II, Beclin1, LAMP2, and Rab7. The activation and inhibition of autophagy by rapamycin and 3-MA were promoted and attenuated histological and renal function in renal I/R rats, respectively. Cytokines TNF-α, IL-6, and HMGB1 were decreased, and IL-10 was further increased after activation of autophagy treated in I/R rats, while 3-MA exacerbated the pro-inflammatory cytokines TNF-α, IL-6, HMGB1, and anti-inflammatory cytokine IL-10 in renal I/R. I/R can activated the autophagy, and autophagy increase mitigated the renal injury by decreasing kidney injury score, levels of Cr and BUN after renal I/R, and inflammation response via regulating the balance of pro-inflammation and anti-inflammation cytokines.

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Abbreviations

3-MA:

3-Methyladenine

AKI:

Acute kidney injury

BUN:

Blood urea nitrogen

BW:

Body Weight

Cr:

Creatinine

ELISA:

Enzyme-linked immunosorbent assay

HMGB1:

High mobility group box 1

HRP:

Horse reddish peroxidase

IL:

Interleukin

I/R:

Ischemia/reperfusion

LAMP:

Lysosome-associated membrane protein type

LC3:

Microtubule-associated protein light chain 3

RT:

Room temperature

RT-PCR:

Transcription-polymerase chain reaction

TNF:

Tumor necrosis factor

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ACKNOWLEDGMENTS

This work was supported by research grants from the National Natural Science Foundation of China (81372033, 81471842) and the Natural Science Foundation of the Tianjin Science Committee (13JCQNJC11400).

Conflict of Interest

The authors declare that they have no competing interests.

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    Authors and Affiliations

    1. Department of Urology Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei Province, 075000, People’s Republic of China

      Haibin Ling

    2. Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin Research Institute of Anesthesiology, Tianjin, 300052, People’s Republic of China

      Hongguang Chen, Yonghao Yu & Keliang Xie

    3. Department of Intensive Care Unit, Shanxi Tumor Hospital, Taiyuan, Shanxi Province, 030013, People’s Republic of China

      Miao Wei

    4. Department of Gynaecology and Obstetrics, Tianjin Hospital, Tianjin, 300211, China

      Xiaoyin Meng

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    1. Haibin Ling
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    Correspondence to Yonghao Yu or Keliang Xie.

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    Haibin Ling, Hongguang Chen and Miao Wei contributed equally to this work.

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    Ling, H., Chen, H., Wei, M. et al. The Effect of Autophagy on Inflammation Cytokines in Renal Ischemia/Reperfusion Injury. Inflammation 39, 347–356 (2016). https://doi.org/10.1007/s10753-015-0255-5

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