Immunoreactivity for myeloperoxidase (MPO) in the vestibule after the injection of bacterial lipopolysaccharide into the middle ear

Watanabe, Kenichi; Jinnouchi, Ken; Yagi, Toshiaki

doi:10.1016/s0385-8146(02)00002-0

Cited by 4 publications

(5 citation statements)

References 27 publications

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“…The activity of MPO, an indicator of neutrophil infiltration was significantly increased in LPS‐induced mice. The immune reactivity of MPO in vivo after injection of LPS has already been demonstrated (Watanabe et al ., 2002). In the current study, MPO activity was observed augmented in the liver and lung tissues of LPS induced mice.…”

Section: Discussionmentioning

confidence: 83%

Betulinic acid inhibits endotoxin‐stimulated phosphorylation cascade and pro‐inflammatory prostaglandin E₂ production in human peripheral blood mononuclear cells

Vijayan

Helen

Luxmi

2011

British J Pharmacology

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BACKGROUND AND PURPOSEBetulinic acid (BA) is a naturally occurring triterpenoid widely distributed throughout the plant kingdom. We previously reported that BA inhibits lipopolysaccharide (LPS)-induced interleukin-6 production through modulation of nuclear factor kB (NF-kB) in human peripheral blood mononuclear cells (hPBMCs). This study attempted to identify other mechanisms through which BA modulates LPS signalling in mononuclear cells. The effects of BA on signalling pathways downstream were focused on in this study. EXPERIMENTAL APPROACHWe determined the ability of BA to interfere with p38 and extracellular regulated kinase (ERK) phosphorylation as well as Akt phosphorylation and nuclear factor-kB activation using LPS-activated hPBMCs as an in vitro model. LPS-induced endotoxin shock in mice was the in vivo model employed. KEY RESULTSBA inhibited LPS-induced COX-2 protein expression and prostaglandin E2 production and also attenuated LPS-induced ERK and Akt phosphorylation, but not p38 in hPBMCs. BA abolished LPS-induced IkBa phosphorylation and thus normalized the levels of IkBa in cytosol. BA also inhibited LPS-induced reactive oxygen species formation and lactate dehydrogenase release. Interestingly, BA improved the life span of mice in endotoxin shock and also inhibited PGE2 production and myeloperoxidase activity in vivo. CONCLUSIONS AND IMPLICATIONSBA modulates LPS-induced COX-2 expression in hPBMCs by inhibiting ERK and Akt pathways as well as by modulating IkBa phosphorylation. At the same time, no cell toxicity was observed. The effect of the drug was confirmed through in vivo experiments. The study gives an insight into the molecular mechanisms of BA. Abbreviations

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Section: Discussionmentioning

confidence: 83%

Betulinic acid inhibits endotoxin‐stimulated phosphorylation cascade and pro‐inflammatory prostaglandin E₂ production in human peripheral blood mononuclear cells

Vijayan

Helen

Luxmi

2011

British J Pharmacology

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“…The subepithelial space of the middle ear mucosa has also been demonstrated to be contiguous with the perilymphatic space (19). Watanabe et al (20) supposed that the inflammatory cytokines spread from the middle ear cavity via blood vessels, rather than perilymphatic fluid, when the neutrophils become activated in the vestibule. As the vestibule is relatively far from the round window, invading substances must diffuse from the round window via the scala tympani and scala vestibuli to the vestibular perilymph.…”

Section: Resultsmentioning

confidence: 99%

“…As the vestibule is relatively far from the round window, invading substances must diffuse from the round window via the scala tympani and scala vestibuli to the vestibular perilymph. The vestibular perilymph is also separated from the cochlear perilymph by the membrana limitans (20). By analysing gentamicin kinetics in inner ear fluid following round window administration, Plontke et al (21) suggested that it was necessary for drug entry into the vestibule to be dominated by interscala exchange rather than by longitudinal spread through the helicotrema.…”

Section: Resultsmentioning

confidence: 99%

Localization of endotoxin in the inner ear following inoculation into the middle ear

Takumida

Anniko

2004

Acta Oto-Laryngologica

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Sensorineural hearing loss is known to be a significant sequela of otitis media (OM). The pathophysiology of such hearing loss in OM is thought to be due to transmission of toxins and other bacterial products through the round window membrane, damaging the hair cells of the basal turn of the cochlea. Other routes, such as those involving the oval window, blood vessels and lymphatics, may also be involved. The purpose of this study was to elucidate the routes from the middle ear cavity to the inner ear and also the distribution pattern of endotoxin in the inner ear after injection of fluorescence-labelled endotoxin into the tympanic cavity and detection of fluorescence in the cochleae, vestibular end organs and facial nerves. This fluorescence was far more intense in the lower turns of the cochlea. These findings suggest that endotoxin can reach the inner ear by various routes, e.g. the round window, blood vessels or lymphatics, and/or interscala exchange, resulting in a disturbance not only of the cochlea but also of the vestibular end organs.

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“…However, previous studies have demonstrated passage of the toxin and cochlear inflammation by a suspected LPSrelated alteration of the membrane permeability or structure (Cureoglu et al, 2005;Darrow et al, 1992;Engel et al, 1995;Goycoolea et al, 1988;Juhn et al, 1989;Kim & Kim, 1995;Morizono & Ikeda, 1990;Paparella et al, 1970;Schachern et al, 1992;Spandow et al, 1988Spandow et al, , 1989Spandow et al, , 1990Takumida & Anniko, 1998, 2004bTrinidad et al, 2005). Another option is a haematogenous route via blood vessels of the inner ear (Watanabe et al, 2002), which are mainly located in the spiral limbus and the lateral cochlear wall (Kastenbauer et al, 2001;Li et al, 2008;Watanabe et al, 2002). Previous findings after LPS exposure-related damage in the endolymphatic compartment suggested blood-labyrinth barrier disruption by the inflammatory molecules and the capability of reaching the endolymph (Li et al, 2008).…”

Section: In Utero Lesion Of the Inner Earmentioning

confidence: 99%

“…induction of inflammation and the modulation of the immune responses (Darrow et al, 1992). It is also associated with functional and morphological inner ear damage in experimental animal models (Guo et al, 1994;Watanabe et al, 2001Watanabe et al, , 2002, which we will discuss in the next paragraph. We hypothesize that this toxin, by means of an intrauterine infection, can play a role in the pathogenesis of congenital SNHL.…”

Section: Introductionmentioning

confidence: 99%

Potential role for lipopolysaccharide in congenital sensorineural hearingloss

Smit

Stokroos

Litjens

et al. 2010

Journal of Medical Microbiology

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Congenital sensorineural hearing loss (SNHL) is common. In the Western world, the incidence is 1-3 per 1000 live births. The aetiology encompasses genetic and non-genetic factors accounting for 55 % and 45 % of cases, respectively. Reports that describe the contribution of intrauterine infection to the occurrence of congenital SNHL are limited, and comparative analysis of the different pathogens is lacking. Lipopolysaccharide (LPS), a product of bacteriolysis, has been demonstrated to be associated with inner ear damage in experimental studies. To elucidate the potential role of this toxin in congenital SNHL and to identify the pathogenesis and transmission routes, we reviewed the literature. We speculate that different routes of exposure to LPS in utero may result in congenital inner ear damage.

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Immunoreactivity for myeloperoxidase (MPO) in the vestibule after the injection of bacterial lipopolysaccharide into the middle ear

Cited by 4 publications

References 27 publications

Betulinic acid inhibits endotoxin‐stimulated phosphorylation cascade and pro‐inflammatory prostaglandin E₂ production in human peripheral blood mononuclear cells

Betulinic acid inhibits endotoxin‐stimulated phosphorylation cascade and pro‐inflammatory prostaglandin E₂ production in human peripheral blood mononuclear cells

Localization of endotoxin in the inner ear following inoculation into the middle ear

Potential role for lipopolysaccharide in congenital sensorineural hearingloss

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Immunoreactivity for myeloperoxidase (MPO) in the vestibule after the injection of bacterial lipopolysaccharide into the middle ear

Cited by 4 publications

References 27 publications

Betulinic acid inhibits endotoxin‐stimulated phosphorylation cascade and pro‐inflammatory prostaglandin E2 production in human peripheral blood mononuclear cells

Betulinic acid inhibits endotoxin‐stimulated phosphorylation cascade and pro‐inflammatory prostaglandin E2 production in human peripheral blood mononuclear cells

Localization of endotoxin in the inner ear following inoculation into the middle ear

Potential role for lipopolysaccharide in congenital sensorineural hearingloss

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Product

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Betulinic acid inhibits endotoxin‐stimulated phosphorylation cascade and pro‐inflammatory prostaglandin E₂ production in human peripheral blood mononuclear cells

Betulinic acid inhibits endotoxin‐stimulated phosphorylation cascade and pro‐inflammatory prostaglandin E₂ production in human peripheral blood mononuclear cells