NLRP3

CATEGORY:
Research

SCREENSHOT:
Oridonin ameliorates noise-induced hearing loss by blocking NLRP3 - NEK7 mediated inflammasome activation

TITLE:
Oridonin ameliorates noise-induced hearing loss by blocking NLRP3 – NEK7 mediated inflammasome activation

CONTENT:
Int Immunopharmacol. 2021 Mar 23;95:107576. doi: 10.1016/j.intimp.2021.107576. Online ahead of print.

ABSTRACT

Inflammation is involved in noise-induced hearing loss (NIHL), but the mechanism is still unknown. The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, which triggers the inflammatory cascade, has been implicated in several inflammatory diseases in response to oxidative stress. However, whether the NLRP3 inflammasome is a key factor for permanent NIHL is still unknown. In this study, quantitative real-time polymerase chain reaction (qPCR), western blot, and enzyme-linked immunosorbent assays (ELISAs) demonstrated that the expression levels of activated caspase-1, interleukin (IL)-1β, IL-18, and NLRP3 were significantly increased in the cochleae of mice exposed to broadband noise (120 dB) for 4 h, compared with the control group. These results indicate that the activation of inflammasomes in the cochleae of mice during the pathological process of NIHL as well as NLRP3, a sensor protein of reactive oxygen species (ROS), may be key factors for inflammasome assembly and subsequent inflammation in cochleae. Moreover, many recent studies have revealed that NEK7 is an important component and regulator of NLRP3 inflammasomes by interacting with NLRP3 directly and that these interactions can be interrupted by oridonin. Here, we further determined that treatment with oridonin could indeed interrupt the interaction between NLRP3 and NEK7 as well as inhibit the downstream inflammasome activation in mouse cochleae after noise exposure. Furthermore, we tested anakinra, another inflammatory inhibitor, and it was shown to partially alleviate the degree of hearing impairment in some frequencies in an NIHL mouse model. These discoveries suggest that inhibiting NLRP3 inflammasomes and the downstream signaling pathway may provide a new strategy for the clinical treatment of NIHL.

PMID:33770730 | DOI:10.1016/j.intimp.2021.107576

SOURCE:
International immunopharmacology

PUBLISHER:

PMID:
pubmed:33770730

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33770730

DOI:
10.1016/j.intimp.2021.107576

DATE – PUBLISHED:
Fri, 26 Mar 2021 06:00:00 -0400

DATE – DOI:
2021-03-23T12:47:43Z

DATE – ADDED:
03/27/21 10:05AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33770730/

LINK – DOI:
https://doi.org/10.1016/j.intimp.2021.107576

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S1567576921002125?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-27T14:05:04+00:00, https://www.hearinglosstreatmentreport.com.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407738/

https://www.ncbi.nlm.nih.gov/pubmed/32774726?dopt=Abstract

Long-term exposure to low-intensity environmental noise aggravates age-related hearing loss via disruption of cochlear ribbon synapses.

Am J Transl Res. 2020;12(7):3674-3687

Authors: Feng S, Yang L, Hui L, Luo Y, Du Z, Xiong W, Liu K, Jiang X

Abstract

Noise pollution is a major public hazard. Previous studies have shown that environmental noise affects the reorganization of the auditory cortex and leads to behavioral abnormality; however, the effects of long-term environmental noise exposure on the inner ear and hearing remain to be elucidated. In this study, we simulated environmental noise with a long-term 70 dB sound pressure level “white” noise, observed its effect on the inner ears of C57BL/6J mice, and developed an in vitro model for mechanistic studies. We found that environmental noise increased the hearing threshold, decreased the auditory response amplitude, and aggravated the range and extent of age-related hearing loss (ARHL), especially in the intermediate frequency band in mice. Cochlear ribbon synapse is the primary site of inner ear injury caused by environmental noise. We also verified, through an in vitro simulation of the excitatory toxicity of glutamate and aging effects, that the activation of NLRP3 inflammasome plays a vital role in the cochlear ribbon synaptic damage. Our results show that long-term exposure to low-intensity environmental noise can lead to hearing loss via the disruption of ribbon synapses, which is caused by an inflammatory reaction. Additionally, environmental noise can further aggravate the progression of ARHL. This study expounded the pathogenesis of the inner ear damage caused by environmental noise exposure and provides a new direction for the prevention and treatment of hearing loss.

PMID: 32774726 [PubMed – as supplied by publisher]