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Histone deacetylase inhibitors up-regulate LL-37 expression independent of toll-like receptor mediated signalling in airway epithelial cells.

Liu Q, Liu J, Roschmann KI, van Egmond D, Golebski K, Fokkens WJ, Wang D, van Drunen CM - J Inflamm (Lond) (2013)

Bottom Line: Our results showed that HDAC inhibitors up-regulated LL-37 gene expression independent of poly (I:C) stimulation in PNEC as well as in NCI-H292 cells.HDAC inhibitors increased LL37 protein expression in NCI-H292 cells but not in PNEC.In conclusion, HDAC inhibitors directly up-regulated LL-37 gene expression in human airway epithelial cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Otolaryngology, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, 200031, China. wangdehuient@sina.com.

ABSTRACT
HDAC inhibitors have been proposed as anticancer agents. However, their roles in innate genes expression remain not well known. Cathelicidin LL-37 is one of the few human bactericidal peptides, but the regulation of histone acetylation on LL-37 expression in airway epithelium remains largely unknown. Therefore, we investigated the effects of two non-selective HDACi, trichostatin A (TSA) and sodium butyrate (SB), on the expression of the cathelicidin LL-37 in human airway epithelial cells. LL37 in human NCI-H292 airway epithelial cells and the primary cultures of normal nasal epithelial cells(PNEC) in response to HDAC inhibitors with or without poly (I:C) stimulation was assessed using real-time PCR and western blot. In parallel, IL-6 expression was evaluated by ELISA. Our results showed that HDAC inhibitors up-regulated LL-37 gene expression independent of poly (I:C) stimulation in PNEC as well as in NCI-H292 cells. HDAC inhibitors increased LL37 protein expression in NCI-H292 cells but not in PNEC. In addition, HDAC inhibitors significantly inhibited poly (I:C)-induced IL-6 production in both of the epithelial cells. In conclusion, HDAC inhibitors directly up-regulated LL-37 gene expression in human airway epithelial cells.

No MeSH data available.


The effect of HDAC inhibitors ( TSA,200 nM; SB,4 Mm) on the LL37 gene expression in the primary nasal epithelial cell. *p<0.05 vs control. Values represent the mean±SD of three independent experiments.
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Figure 2: The effect of HDAC inhibitors ( TSA,200 nM; SB,4 Mm) on the LL37 gene expression in the primary nasal epithelial cell. *p<0.05 vs control. Values represent the mean±SD of three independent experiments.

Mentions: The sinonasal tract lined by respiratory epithelium plays an important role in airway immunity. The only human cathelicidin LL37 first identified in neutrophils was shown to be expressed in surface epithelial cells of the conducting airways [9]. To verify whether HDAC inhibitors induce LL37 gene expression in upper airway epithelial cells, we cultured the human nasal epithelial cells and performed the stimulation experiments in the primary cells. Our results demonstrated that the HDAC inhibitors had a similar effect on the LL37 mRNA expression as they did in H292 cells (Figure 2).


Histone deacetylase inhibitors up-regulate LL-37 expression independent of toll-like receptor mediated signalling in airway epithelial cells.

Liu Q, Liu J, Roschmann KI, van Egmond D, Golebski K, Fokkens WJ, Wang D, van Drunen CM - J Inflamm (Lond) (2013)

The effect of HDAC inhibitors ( TSA,200 nM; SB,4 Mm) on the LL37 gene expression in the primary nasal epithelial cell. *p<0.05 vs control. Values represent the mean±SD of three independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3643837&req=5

Figure 2: The effect of HDAC inhibitors ( TSA,200 nM; SB,4 Mm) on the LL37 gene expression in the primary nasal epithelial cell. *p<0.05 vs control. Values represent the mean±SD of three independent experiments.
Mentions: The sinonasal tract lined by respiratory epithelium plays an important role in airway immunity. The only human cathelicidin LL37 first identified in neutrophils was shown to be expressed in surface epithelial cells of the conducting airways [9]. To verify whether HDAC inhibitors induce LL37 gene expression in upper airway epithelial cells, we cultured the human nasal epithelial cells and performed the stimulation experiments in the primary cells. Our results demonstrated that the HDAC inhibitors had a similar effect on the LL37 mRNA expression as they did in H292 cells (Figure 2).

Bottom Line: Our results showed that HDAC inhibitors up-regulated LL-37 gene expression independent of poly (I:C) stimulation in PNEC as well as in NCI-H292 cells.HDAC inhibitors increased LL37 protein expression in NCI-H292 cells but not in PNEC.In conclusion, HDAC inhibitors directly up-regulated LL-37 gene expression in human airway epithelial cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Otolaryngology, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, 200031, China. wangdehuient@sina.com.

ABSTRACT
HDAC inhibitors have been proposed as anticancer agents. However, their roles in innate genes expression remain not well known. Cathelicidin LL-37 is one of the few human bactericidal peptides, but the regulation of histone acetylation on LL-37 expression in airway epithelium remains largely unknown. Therefore, we investigated the effects of two non-selective HDACi, trichostatin A (TSA) and sodium butyrate (SB), on the expression of the cathelicidin LL-37 in human airway epithelial cells. LL37 in human NCI-H292 airway epithelial cells and the primary cultures of normal nasal epithelial cells(PNEC) in response to HDAC inhibitors with or without poly (I:C) stimulation was assessed using real-time PCR and western blot. In parallel, IL-6 expression was evaluated by ELISA. Our results showed that HDAC inhibitors up-regulated LL-37 gene expression independent of poly (I:C) stimulation in PNEC as well as in NCI-H292 cells. HDAC inhibitors increased LL37 protein expression in NCI-H292 cells but not in PNEC. In addition, HDAC inhibitors significantly inhibited poly (I:C)-induced IL-6 production in both of the epithelial cells. In conclusion, HDAC inhibitors directly up-regulated LL-37 gene expression in human airway epithelial cells.

No MeSH data available.