D inflammatory responses in cochlear injury and repair has not been

D inflammatory responses in cochlear injury and repair has not been well established. Because treatments with steroid hormones are known to have a protective effect and because the protective effect is mediated via NF-B and TNF-, which are both immune and inflammatory regulators, the inflammatory PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19854492 response likely contributes to sensory cell damage. IPA allowed us to predict the transcriptional regulators that would be involved in modulating the differential expression of these genes and whether the regulators activate or inhibit the genes of interest. Using this bioinformatics tool, we determined the common regulators in mice and rats for the genes that showed differential expression following acoustic overstimulation. Lipopolysaccharide is an endotoxin released from Gram-negative bacteria. This molecule is able to provoke a strong immune defense response via a Tlr4dependent pathway. The identification of this molecule suggests that the Tlr4 pathway is activated, possibly by the endogenous molecules released from the damaged tissues. IL6 and TNF are inflammatory molecules, and their involvement in acoustic injury has been reported. Interferon gamma is an important activator of macrophages and induces the expression of major histocompatibility complex II, an antigen presenting protein. We have observed an increase in the expression of major histocompatibility complex II in mononuclear phagocytes of the cochlea following acoustic injury, suggesting the activation of an antigen-presenting function. Creb1 encodes cAMPresponsive element binding protein 1, and this protein is involved in the transcriptional regulation of cAMP-inducible genes. Together, this bioinformatics analysis of the potential upstream regulators reveals the potential molecular players and pathways involved in the regulation of the cochlear response to acoustic trauma. Hear Res. Author manuscript; available in PMC 2017 March 01. Author Manuscript Author Manuscript Author Manuscript Author Manuscript Yang et al. Page 12 Previous investigations have implicated multiple genes in the cochlear responses to acoustic trauma. However, many of the previously reported genes were not identified in the current study. This discrepancy could result from the differences in the HC-067047 experimental paradigms, such as the noise level used, the time of sample collection and the cell populations sampled. In addition, the differences in the expression analysis platforms used in the different studies could contribute to this discrepancy. RNA-sequencing analysis simultaneously compares a large number of genes, yet the sample sizes are relatively small due to high sequencing costs. Small sample sizes compromise the power of the analysis. Moreover, in our recent variation analysis of RNA-sequencing data, we found a marked increase in the variations in cochlear gene expression following acoustic trauma. These unstable genes are functionally associated with cell death, apoptosis and macro-molecular metabolisms. Clearly, our RNA-sequencing analysis was unable to identify these genes because of these variations. It would be expected that as the sample size increases, more differently Sodium laureth sulfate price expressed genes could be identified. Despite the presence of a marked overlap in the functional relevance of the differentially expressed genes, the gene sets identified in the two species differed considerably. This difference could suggest species-specific differences; however, several confounding factors complicate this inter.D inflammatory responses in cochlear injury and repair has not been well established. Because treatments with steroid hormones are known to have a protective effect and because the protective effect is mediated via NF-B and TNF-, which are both immune and inflammatory regulators, the inflammatory PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19854492 response likely contributes to sensory cell damage. IPA allowed us to predict the transcriptional regulators that would be involved in modulating the differential expression of these genes and whether the regulators activate or inhibit the genes of interest. Using this bioinformatics tool, we determined the common regulators in mice and rats for the genes that showed differential expression following acoustic overstimulation. Lipopolysaccharide is an endotoxin released from Gram-negative bacteria. This molecule is able to provoke a strong immune defense response via a Tlr4dependent pathway. The identification of this molecule suggests that the Tlr4 pathway is activated, possibly by the endogenous molecules released from the damaged tissues. IL6 and TNF are inflammatory molecules, and their involvement in acoustic injury has been reported. Interferon gamma is an important activator of macrophages and induces the expression of major histocompatibility complex II, an antigen presenting protein. We have observed an increase in the expression of major histocompatibility complex II in mononuclear phagocytes of the cochlea following acoustic injury, suggesting the activation of an antigen-presenting function. Creb1 encodes cAMPresponsive element binding protein 1, and this protein is involved in the transcriptional regulation of cAMP-inducible genes. Together, this bioinformatics analysis of the potential upstream regulators reveals the potential molecular players and pathways involved in the regulation of the cochlear response to acoustic trauma. Hear Res. Author manuscript; available in PMC 2017 March 01. Author Manuscript Author Manuscript Author Manuscript Author Manuscript Yang et al. Page 12 Previous investigations have implicated multiple genes in the cochlear responses to acoustic trauma. However, many of the previously reported genes were not identified in the current study. This discrepancy could result from the differences in the experimental paradigms, such as the noise level used, the time of sample collection and the cell populations sampled. In addition, the differences in the expression analysis platforms used in the different studies could contribute to this discrepancy. RNA-sequencing analysis simultaneously compares a large number of genes, yet the sample sizes are relatively small due to high sequencing costs. Small sample sizes compromise the power of the analysis. Moreover, in our recent variation analysis of RNA-sequencing data, we found a marked increase in the variations in cochlear gene expression following acoustic trauma. These unstable genes are functionally associated with cell death, apoptosis and macro-molecular metabolisms. Clearly, our RNA-sequencing analysis was unable to identify these genes because of these variations. It would be expected that as the sample size increases, more differently expressed genes could be identified. Despite the presence of a marked overlap in the functional relevance of the differentially expressed genes, the gene sets identified in the two species differed considerably. This difference could suggest species-specific differences; however, several confounding factors complicate this inter.