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Rapamycin Alleviates Hormone Imbalance-Induced Chronic Nonbacterial Inflammation in Rat Prostate Through Activating Autophagy via the mTOR/ULK1/ATG13 Signaling Pathway

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Abstract

Chronic prostatitis (CP) is a clinically common disease with high morbidity. It affects the patients’ quality of life (QoL) as well as physical and mental health seriously due to the recurring symptoms of lower urinary tract and genitalia. As the opinions about the etiology of CP are still not uniform, it is very difficult to be treated or even cured. Autophagy is a highly conserved physiological function which is widely found in eukaryotic cells. In general, cells maintain a certain level of autophagy under physiological conditions, and the basal level of autophagy can be regulated by a variety of autophagy-related genes under stress such as hunger, infection, trauma, and other circumstances. Therefore, the main purpose of this study is to investigate the role of autophagy in chronic nonbacterial prostatitis (CNP, also called CP). In this paper, we established the CNP model via hypodermic injection of 17β-estradiol and subsequently abdominal rapamycin (a common autophagy inducer) treatment based on castrated rats. Then, the expression of nuclear factor-κB (NF-κB), interleukin-1β (IL-1β), and autophagy-related markers as well as autophagosome formation in prostate tissues, peripheral blood mononuclear cells (PBMCs), and serum of rats were evaluated respectively. In addition to some histological changes in the prostate tissues, we found the levels of NF-κB and IL-1β were significantly increased in the model group, along with significantly suppressed autophagy, whereas rapamycin could reverse these effects which involved in the mTOR/ULK1/ATG13 signaling pathway. In conclusion, our results suggested that rapamycin could ameliorate hormone imbalance-induced CNP by activating autophagy.

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Abbreviations

CP:

Chronic prostatitis

CNP:

Chronic nonbacterial prostatitis

NF-κB:

Nuclear factor-κB

IL-1β:

Interleukin-1β

ABP:

Acute bacterial prostatitis

CBP:

Chronic bacterial prostatitis

CP/CPPS:

Chronic prostatitis/chronic pelvic pain syndrome

AIP:

Asymptomatic inflammatory prostatitis

NIH:

National Institutes of Health

QoL:

Quality of life

IBD:

Inflammatory bowel disease

qRT-PCR:

Quantitative real-time PCR

HE:

Hematoxylin-eosin

ELISA:

Enzyme-linked immunosorbent assay

PBMCs:

Peripheral blood mononuclear cells

IHC:

Immunohistochemistry

PBS:

Phosphate-buffered saline

ATG:

Autophagy-related gene

SDS:

Sodium dodecyl sulfate

BSA:

Bull serum albumin

TBS:

Tris-buffered saline

TBST:

Tris-buffered saline with Tween 20

mTOR:

Mammalian target of rapamycin

ULK1:

Unc-51 like autophagy activating kinase 1

T:

Testosterone

E2:

Estrogen

RAPA:

Rapamycin

P-ULK1:

Phosphorylated ULK1

Ser:

Serine

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Funding

This study was supported by grant from the National Natural Science Foundation of China (Nos. 81470923, 81470986, 81770078, and 81770688).

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Authors and Affiliations

  1. Department of Urology, Renmin Hospital of Wuhan University, Wuhan, 430060, China

    Yang Su, Jingxiao Lu, Cong Qin & Jie Zhang

  2. Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China

    Xianguo Chen & Chaozhao Liang

  3. Huangshi Central Hospital, Hubei Polytechnic University, Huangshi, 435000, China

    Pengcheng Luo & Jie Zhang

Authors
  1. Yang Su
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  2. Jingxiao Lu
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Correspondence to Jie Zhang.

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This study was approved by the Animal Care and Use Committee of Wuhan University Renmin Hospital. All animal care and experimental procedures were performed in accordance with the guidelines of Wuhan University Renmin Hospital.

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The authors declare that they have no conflict of interest.

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Su, Y., Lu, J., Chen, X. et al. Rapamycin Alleviates Hormone Imbalance-Induced Chronic Nonbacterial Inflammation in Rat Prostate Through Activating Autophagy via the mTOR/ULK1/ATG13 Signaling Pathway. Inflammation 41, 1384–1395 (2018). https://doi.org/10.1007/s10753-018-0786-7

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