Microarray analysis of microRNA expression in LPS induced inflammation of human middle ear epithelial cells (HMEECs)

Song, Jae Jun; Kwon, Seong Keun; Cho, Chang Gun; Park, Seok Won; Chae, Sung Won

doi:10.1016/j.ijporl.2011.02.001

Cited by 20 publications

(20 citation statements)

References 29 publications

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“…TLR signaling initiates miR-146a/b expression which is in turn crucial for finely tuning the immune response by targeting key intermediaries in the TLR signaling cascade, tumor necrosis factor receptor-associated factor 6 (TRAF6) and interleukin-1 receptor-associated kinase 1 (IRAK1), and to a lesser extent cytokines, cytokine receptors, myeloid differentiation primary response gene 88 (MyD88) and TLRs. [23–26] While Song et al previously investigated miRNA expression in lipopolysaccharide (LPS)-stimulated HMEEC, and did not report a change in miR-146 expression,[4] the authors used a shorter treatment time (two hours) and different stimuli than those herein.…”

Section: Discussionmentioning

confidence: 99%

Association of microRNA 146 with middle ear hyperplasia in pediatric otitis media

Samuels

Yan

Khampang

et al. 2016

International Journal of Pediatric Otorhinolaryngology

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Objective Toll-like receptor signaling activated by bacterial otitis media pathogens in the middle ear has been shown to play a key role in OM susceptibility, pathogenesis and recovery. Recent studies implicate microRNA 146 (miR-146) in regulation of inflammation via negative feedback of toll-like receptor signaling (TLR) in a wide variety of tissues, however its involvement in otitis media is unknown. Methods Human middle ear epithelial cells were stimulated with proinflammatory cytokines, interluekin 1 beta or tumor necrosis factor alpha, for two to twenty-four hours. Middle ear biopsies were collected from children with otitis media with effusion (n=20), recurrent otitis media (n=9), and control subjects undergoing cochlear implantation (n=10). miR-146a, miR-146b expression was assayed by quantitative PCR (qPCR). Expression of miR-146 targets involved in TLR signaling, IRAK1 and TRAF6, was assayed by qPCR in middle ear biopsies. Middle ear biopsies were cryosectioned and epithelial thickness measured by a certified pathologist. Results Proinflammatory cytokines induced expression of miR-146 in middle ear epithelial cells in vitro. Middle ear miR-146a and miR-146b expression was elevated in otitis media patients relative to control subjects and correlated with middle ear epithelial thickness. A trend towards inverse correlation was observed between miR-146 and TRAF6 expression in the clinical population. Conclusions This report is the first to assess miRNA expression in a clinical population with OM. Findings herein suggest miR-146 may play a role in OM.

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Section: Discussionmentioning

confidence: 99%

Association of microRNA 146 with middle ear hyperplasia in pediatric otitis media

Samuels

Yan

Khampang

et al. 2016

International Journal of Pediatric Otorhinolaryngology

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“…LPS has been shown to produce IL-1β, IL-6, TNFα, COX-1, and COX-2 in the middle ear [27,55,56]. As such, it has been used in numerous studies to induce experimental otitis media [57][58][59]. What is not known is how LPS induces inflammation.…”

Section: Cytokine Production Due To Lipopolysaccharide (Lps)-induced mentioning

confidence: 99%

Cytokine Responses in the Common Cold and Otitis Media

Wine

Alper

2012

Curr Allergy Asthma Rep

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Cytokines are a group of diverse molecules that influence the function of every organ system. They are most well studied in their effects on the immune system and their integral role in mediating inflammation. The common cold and otitis media are two such disease states, and much has been learned about the various effects of cytokines in each disease. Most often the viruses isolated include rhinovirus (RV), respiratory syncytial virus (RSV), adenovirus, coronavirus, and picornavirus. Otitis media, sinusitis, bronchiolitis, pneumonia, and asthma exacerbation are commonly accepted as complications of viral upper respiratory tract infections. Furthermore, otitis media and upper respiratory infections are inextricably linked in that the majority (>70 %) of cases of acute otitis media occur as complications of the common cold. Cytokine polymorphisms have been associated with the severity of colds as well as the frequency of otitis media. This article attempts to update the reader on various studies that have recently been published regarding the role of cytokines in these two disease entities.

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“…Previously, Samuels et al (49) reported the induction of miR‐146 in response to inflammatory stimuli (IL‐1β and TNF‐α) in HMEEC lysates, not secreted exosomes. Likewise, other miRNAs were regulated in HMEEC lysates in response to LPS challenge (50). None of the miRNAs characterized in these two studies were found in ours.…”

Section: Discussionmentioning

confidence: 99%

Nontypeable Haemophilus influenzae lysates increase heterogeneous nuclear ribonucleoprotein secretion and exosome release in human middle‐ear epithelial cells

et al. 2018

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Nontypeable Haemophilus influenzae (NTHi), one of the most common acute otitis media (OM) pathogens, is postulated to promote middle-ear epithelial remodeling in the progression of OM from acute to chronic. The goal of this study was to examine early quantitative proteomic secretome effects of NTHi lysate exposure in a human middle-ear epithelial cell (HMEEC) line. NTHi lysates were used to stimulate HMEEC, and conditional quantitative stable isotope labeling with amino acids in cell culture of cell secretions was performed. Mass spectrometry analysis identified 766 proteins across samples. Of interest, several heterogeneous nuclear ribonucleoproteins (hnRNPs) were regulated by NTHi lysate treatment, especially hnRNP A2B1 and hnRNP Q, known to be implicated in microRNA (miRNA) packaging in exosomes. After purification, the presence of exosomes in HMEEC secretions was characterized by dynamic light scattering (<100 nm), transmission electron microscopy, and CD63/heat shock protein 70 positivity. hnRNP A2B1 and hnRNP Q were confirmed to be found in exosomes by Western blot and proteomic analysis. Finally, exosomal miRNA content comprised 110 unique miRNAs, with 5 found to be statistically induced by NTHi lysate (miR-378a-3p + miR-378i, miR-200a-3p, miR-378g, miR30d-5p, and miR-222-3p), all known to target innate immunity genes. This study demonstrates that NTHi lysates promote release of miRNA-laden exosomes from middle-ear epithelium in vitro. -Val, S., Krueger, A., Poley, M., Cohen, A., Brown, K., Panigrahi, A., Preciado, D. Nontypeable Haemophilus influenzae lysates increase heterogeneous nuclear ribonucleoprotein secretion and exosome release in human middle-ear epithelial cells.

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Microarray analysis of microRNA expression in LPS induced inflammation of human middle ear epithelial cells (HMEECs)

Cited by 20 publications

References 29 publications

Association of microRNA 146 with middle ear hyperplasia in pediatric otitis media

Association of microRNA 146 with middle ear hyperplasia in pediatric otitis media

Cytokine Responses in the Common Cold and Otitis Media

Nontypeable Haemophilus influenzae lysates increase heterogeneous nuclear ribonucleoprotein secretion and exosome release in human middle‐ear epithelial cells

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