Lipopolysaccharide disrupts the cochlear blood-labyrinth barrier by activating perivascular resident macrophages and up-regulating MMP-9

Ying, Jiang; Zhang, Jie; Rao, Yufang; Chen, Junhong; Chen, Kai; Tang, Yuedi

doi:10.1016/j.ijporl.2019.109656

Cited by 21 publications

(11 citation statements)

References 41 publications

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“…Mononuclear phagocytic cells enter the spiral ligament when the mice are treated with LPS, resulting in an increase in the number of CCR2(+) inflammatory monocytes in the inner ear, which in turn causes the cochlear inflammatory response [14,15]. Therefore, when LPS-induced inflammation becomes severe or persistent, the cochlear blood-labyrinth barrier will be disrupted and cause pathological changes in the inner ear, including bleeding and inflammatory cell recruitment, eventually lead to hearing loss [[16], [17], [18]].…”

Section: Introductionmentioning

confidence: 99%

The nuclear transcription factor FoxG1 affects the sensitivity of mimetic aging hair cells to inflammation by regulating autophagy pathways

et al. 2020

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Inflammation is a self-defense response to protect individuals from infection and tissue damage, but excessive or persistent inflammation can have adverse effects on cell survival. Many individuals become especially susceptible to chronic-inflammation-induced sensorineural hearing loss as they age, but the intrinsic molecular mechanism behind aging individuals' increased risk of hearing loss remains unclear. FoxG1 (forkhead box transcription factor G1) is a key transcription factor that plays important roles in hair cell survival through the regulation of mitochondrial function, but how the function of FoxG1 changes during aging and under inflammatory conditions is unknown. In this study, we first found that FoxG1 expression and autophagy both increased gradually in the low concentration lipopolysaccharide (LPS)-induced inflammation model, while after high concentration of LPS treatment both FoxG1 expression and autophagy levels decreased as the concentration of LPS increased. We then used siRNA to downregulate Foxg1 expression in hair cell-like OC-1 cells and found that cell death and apoptosis were significantly increased after LPS injury. Furthermore, we used d-galactose (D-gal) to create an aging model with hair cell-like OC-1 cells and cochlear explant cultures in vitro and found that the expression of Foxg1 and the level of autophagy were both decreased after D-gal and LPS co-treatment. Lastly, we knocked down the expression of Foxg1 under aged inflammation conditions and found increased numbers of dead and apoptotic cells. Together these results suggest that FoxG1 affects the sensitivity of mimetic aging hair cells to inflammation by regulating autophagy pathways.

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Section: Introductionmentioning

confidence: 99%

The nuclear transcription factor FoxG1 affects the sensitivity of mimetic aging hair cells to inflammation by regulating autophagy pathways

et al. 2020

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“…NLRP3 inflammasomes can cause pyroptosis (19) [234], which also produces cochlear damage [32] (21). NLRP3 can also initiate the activation of cochlear macrophages (18) [32], which can increase the BLB permeability and induce sterile cochlear inflammation (20) [22,235,236], leading to hearing loss (22) [22,236].…”

Section: Is Gut Dysbiosis Associated With Age-related Hearing Loss?mentioning

confidence: 99%

Age-Related Hearing Loss: The Link between Inflammaging, Immunosenescence, and Gut Dysbiosis

Kociszewska

Vlajkovic²

2022

IJMS

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This article provides a theoretical overview of the association between age-related hearing loss (ARHL), immune system ageing (immunosenescence), and chronic inflammation. ARHL, or presbyacusis, is the most common sensory disability that significantly reduces the quality of life and has a high economic impact. This disorder is linked to genetic risk factors but is also influenced by a lifelong cumulative effect of environmental stressors, such as noise, otological diseases, or ototoxic drugs. Age-related hearing loss and other age-related disorders share common mechanisms which often converge on low-grade chronic inflammation known as “inflammaging”. Various stimuli can sustain inflammaging, including pathogens, cell debris, nutrients, and gut microbiota. As a result of ageing, the immune system can become defective, leading to the accumulation of unresolved inflammatory processes in the body. Gut microbiota plays a central role in inflammaging because it can release inflammatory mediators and crosstalk with other organ systems. A proinflammatory gut environment associated with ageing could result in a leaky gut and the translocation of bacterial metabolites and inflammatory mediators to distant organs via the systemic circulation. Here, we postulate that inflammaging, as a result of immunosenescence and gut dysbiosis, accelerates age-related cochlear degeneration, contributing to the development of ARHL. Age-dependent gut dysbiosis was included as a hypothetical link that should receive more attention in future studies.

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“…In contrast, in a eubiotic state, the BLB protects the cochlea from pathogens, which would otherwise compromise cochlear integrity, causing inflammation and injury. This can be postulated based on evidence that the BBB [189][190][191] and the BLB [192,193] increase their permeability in response to the increased presence of the bacterial metabolite LPS.…”

Section: Could There Be a Similar Connection To The Inner Ear?mentioning

confidence: 99%

“…The BLB limits the extravasation of infiltrating leukocytes from the circulation to reduce cochlear damage from inflammation [194]. However, recent evidence suggests that BLB dysfunction can also occur during cochlear inflammation, which impacts the ability of the BLB to limit the entry of immune cells and inflammatory or infectious agents into the cochlea, which can exacerbate cochlear damage [192,194,208]. Similar mechanisms have been implicated in the pathogenesis of almost all major causes of acquired hearing loss, including acoustic trauma, ototoxicity, and age-related hearing loss [194,209,210].…”

Section: Innate Cochlear Immunity and Blbmentioning

confidence: 99%

The Link between Gut Dysbiosis Caused by a High-Fat Diet and Hearing Loss

Kociszewska

Chan

Thorne

et al. 2021

IJMS

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This review aims to provide a conceptual and theoretical overview of the association between gut dysbiosis and hearing loss. Hearing loss is a global health issue; the World Health Organisation (WHO) estimates that 2.5 billion people will be living with some degree of hearing loss by 2050. The aetiology of sensorineural hearing loss (SNHL) is complex and multifactorial, arising from congenital and acquired causes. Recent evidence suggests that impaired gut health may also be a risk factor for SNHL. Inflammatory bowel disease (IBD), type 2 diabetes, diet-induced obesity (DIO), and high-fat diet (HFD) all show links to hearing loss. Previous studies have shown that a HFD can result in microangiopathy, impaired insulin signalling, and oxidative stress in the inner ear. A HFD can also induce pathological shifts in gut microbiota and affect intestinal barrier (IB) integrity, leading to a leaky gut. A leaky gut can result in chronic systemic inflammation, which may affect extraintestinal organs. Here, we postulate that changes in gut microbiota resulting from a chronic HFD and DIO may cause a systemic inflammatory response that can compromise the permeability of the blood–labyrinth barrier (BLB) in the inner ear, thus inducing cochlear inflammation and hearing deficits.

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Lipopolysaccharide disrupts the cochlear blood-labyrinth barrier by activating perivascular resident macrophages and up-regulating MMP-9

Cited by 21 publications

References 41 publications

The nuclear transcription factor FoxG1 affects the sensitivity of mimetic aging hair cells to inflammation by regulating autophagy pathways

The nuclear transcription factor FoxG1 affects the sensitivity of mimetic aging hair cells to inflammation by regulating autophagy pathways

Age-Related Hearing Loss: The Link between Inflammaging, Immunosenescence, and Gut Dysbiosis

The Link between Gut Dysbiosis Caused by a High-Fat Diet and Hearing Loss

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