ERK2-Dependent Activation of c-Jun Is Required for Nontypeable <i>Haemophilus influenzae</i>-Induced CXCL2 Upregulation in Inner Ear Fibrocytes

Oh, Seong-Hwan; Woo, Jeong Im; Lim, David J.; Moon, Sangook

doi:10.4049/jimmunol.1103182

Cited by 19 publications

(25 citation statements)

References 87 publications

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“…This also provides a molecular basis for the transient and permanent sensorineural hearing loss often reported with acute OM. This parallels findings from other laboratories showing the fibrocytes of the cochlear lateral wall are capable of expressing inflammatory cytokines following bacterial stimulation of the middle ear (Woo et al, 2010; Oh et al, 2012). …”

Section: Discussionsupporting

confidence: 89%

“…Because inner ear function is largely dependent on proper ion and fluid balances, any compromise of these functions would lead to hearing loss. It was discussed above that the fibrocytes of the lateral wall are significantly affected by middle ear inflammation (Woo et al, 2010; Oh et al, 2012). This would have an impact on K + ion transport and its recycling into endolymph.…”

Section: Discussionmentioning

confidence: 99%

“…Previous DNA array screening studies showed cytokine genes are upregulated in the cochleas of BALB/c mice given transtympanic heat-killed bacteria and in cochleas of C3H/HeJ mice with chronic middle ear inflammation (Ghaheri et al, 2007; Ghaheri et al, 2007; MacArthur et al, 2011; Tokarz et al, 2013; MacArthur et al, 2013b). These inflammatory cytokines are predominantly distributed in the cochlear lateral wall as inoculation of middle ears with bacterial components also causes decrease in cochlear blood flow, stria vascularis damage, cytokine expression by spiral ligament fibrocytes, and decreased auditory function (Ichimiya et al, 2003; Sone et al, 2003; MacArthur and Trune, 2006; Moon et al, 2006; Moon et al, 2007; Tsuprun et al, 2008; Woo et al, 2010; Oh et al, 2012). Chronic OM leads to even more significant and permanent inner ear pathology (Cureoglu et al, 2005; MacArthur and Trune, 2006; MacArthur et al, 2008; Joglekar et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Correlative mRNA and protein expression of middle and inner ear inflammatory cytokines during mouse acute otitis media

et al. 2015

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Although the inner ear has long been reported to be susceptible to middle ear disease, little is known of the inflammatory mechanisms that might cause permanent sensorineural hearing loss. Recent studies have shown inner ear tissues are capable of expressing inflammatory cytokines during otitis media. However, little quantitative information is available concerning cytokine gene expression in the inner ear and the protein products that result. Therefore, this study was conducted of mouse middle and inner ear during acute otitis media to measure the relationship between inflammatory cytokine genes and their protein products with quantitative RT-PCR and ELISA, respectively. Balb/c mice were inoculated transtympanically with heat-killed Haemophilus influenzae and middle and inner ear tissues collected for either quantitative RT-PCR microarrays or ELISA multiplex arrays. mRNA for several cytokine genes was significantly increased in both the middle and inner ear at 6 hours. In the inner ear, these included MIP-2 (448 fold), IL-6 (126 fold), IL-1β (7.8 fold), IL-10 (10.7 fold), TNFα (1.8 fold), and IL-1α (1.5 fold). The 24 hour samples showed a similar pattern of gene expression, although generally at lower levels. In parallel, the ELISA showed the related cytokines were present in the inner ear at concentrations higher by 2 to 122 fold higher at 18 hours, declining slightly from there at 24 hours. Immunohistochemistry with antibodies to a number of these cytokines demonstrated they occurred in greater amounts in the inner ear tissues. These findings demonstrate considerable inflammatory gene expression and gene products in the inner ear following acute otitis media. These higher cytokine levels suggest one potential mechanism for the permanent hearing loss seen in some cases of acute and chronic otitis media.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Correlative mRNA and protein expression of middle and inner ear inflammatory cytokines during mouse acute otitis media

et al. 2015

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“…Spiral ligament fibrocytes have been suggested to play an important role in cochlear inflammation through the upregulation of chemokines (Moon et al, 2006; Moon et al, 2007; Oh et al, 2012; Woo et al, 2010; Woo et al, 2015), and resident macrophages, always present in the spiral ligament, are activated in response to various types of insults (Fujioka et al, 2014b). Inflammatory responses usually start at the lateral wall with macrophages migrating from the spiral ligament into the scala vestibuli and scala tympani, but never penetrating into the scala media (see Fig.…”

Section: Lds In the Cochlea: Part Of An Anti-inflammatory Mechanism?mentioning

confidence: 99%

Biology and pathobiology of lipid droplets and their potential role in the protection of the organ of Corti

Urrutia

Kalinec

2015

Hearing Research

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The current review article seeks to extend our understanding on the role of lipid droplets within the organ of Corti. In addition to presenting an overview of the current information about the origin, structure and function of lipid droplets we draw inferences from the collective body of knowledge about this cellular organelle to build a conceptual framework to better understanding their role in auditory function. This conceptual model considers that lipid droplets play a significant role in the synthesis, storage, and release of lipids and proteins for energetic use and/or modulating cell signaling pathways. We describe the role and mechanism by which LD play a role in human diseases, and we also review emerging data from our laboratory revealing the potential role of lipid droplets from Hensen cells in the auditory organ. We suggest that lipid droplets might help to develop rapidly and efficiently the resolution phase of inflammatory responses in the mammalian cochlea, preventing inflammatory damage of the delicate inner ear structures and, consequently, sensorineural hearing loss.

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“…Binding of p65 NF-κB to the enhancer region of the MCP-1/CCL2 gene was determined as described (11). Briefly, the RSL cells were treated for 2 h with the NTHi lysate in the presence or absence of rhIL-10 and fixed with 1% formaldehyde for 10 min.…”

Section: Methodsmentioning

confidence: 99%

IL-10/HMOX1 Signaling Modulates Cochlear Inflammation via Negative Regulation of MCP-1/CCL2 Expression in Cochlear Fibrocytes

Woo

Kil

et al. 2015

The Journal of Immunology

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Cochlear inflammatory diseases such as tympanogenic labyrinthitis are associated with acquired sensorineural hearing loss. Although otitis media is extremely frequent in children, tympanogenic labyrinthitis is not commonly observed, which suggests the existence of a potent anti-inflammatory mechanism modulating cochlear inflammation. In this study, we aim to determine the molecular mechanism involved in cochlear protection from inflammation-mediated tissue damage, focusing on interleukin-10 (IL-10) and hemoxygenase-1 (HMOX1) signaling. We demonstrated that IL-10 receptors (IL-10Rs) are expressed in the cochlear lateral wall of mice and rats, particularly in the spiral ligament fibrocytes (SLFs). The rat SLF cell line (RSL) was found to inhibit nontypeable H. influenzae (NTHi)-induced up-regulation of monocyte chemotactic protein-1 (MCP-1/CCL2) in response to IL-10. This inhibition was suppressed by silencing IL-10R1 and was mimicked by cobalt protoporphyrin IX (CoPP) and carbon monoxide-releasing molecule-2 (CORM-2). In addition, IL-10 appeared to suppress monocyte recruitment through reduction of NTHi-induced RSL-derived chemoattractants. Silencing of HMOX1 was found to attenuate the inhibitory effect of IL-10 on NTHi-induced MCP-1/CCL2 up-regulation. Chromatin immunoprecipitation (ChIP) assays showed that IL-10 inhibits NTHi-induced binding of p65 NF-κB to the distal motif in the promoter region of MCP-1/CCL2, resulting in suppression of NTHi-induced NF-κB activation. Furthermore, IL-10 deficiency appeared to significantly affect cochlear inflammation induced by intratympanic injections of NTHi. Taken together, our results suggest that IL-10/HMOX1 signaling is involved in modulation of cochlear inflammation through inhibition of MCP-1/CCL2 regulation in SLFs, implying therapeutic potential of a carbon monoxide (CO)-based approach for inflammation-associated cochlear diseases.

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ERK2-Dependent Activation of c-Jun Is Required for Nontypeable Haemophilus influenzae-Induced CXCL2 Upregulation in Inner Ear Fibrocytes

Cited by 19 publications

References 87 publications

Correlative mRNA and protein expression of middle and inner ear inflammatory cytokines during mouse acute otitis media

Correlative mRNA and protein expression of middle and inner ear inflammatory cytokines during mouse acute otitis media

Biology and pathobiology of lipid droplets and their potential role in the protection of the organ of Corti

IL-10/HMOX1 Signaling Modulates Cochlear Inflammation via Negative Regulation of MCP-1/CCL2 Expression in Cochlear Fibrocytes

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