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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.


Related in: MedlinePlus

Real-time polymerase chain reaction analysis of expression of LL-37 in H292 cells in response to poly(I:C) with or without TSA. (A): The mRNA expression of LL-37 at different concentration of TSA in response to the poly(I:C). (B): Cells were stimulated with different concentration of poly(I:C) for 24 h in the presence or absence of TSA(200 nM). (C): The effect of SB on the LL37 gene expression. *p<0.05 vs control. Values represent the mean±SD of three independent experiments.
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Figure 1: Real-time polymerase chain reaction analysis of expression of LL-37 in H292 cells in response to poly(I:C) with or without TSA. (A): The mRNA expression of LL-37 at different concentration of TSA in response to the poly(I:C). (B): Cells were stimulated with different concentration of poly(I:C) for 24 h in the presence or absence of TSA(200 nM). (C): The effect of SB on the LL37 gene expression. *p<0.05 vs control. Values represent the mean±SD of three independent experiments.

Mentions: Antibacterial peptides are an integral part of the epithelial defence barrier that provides immediate protection against infection. To characterize the role of epigenetics in the expression of human cathelicidin, we assessed LL-37 expression with or without of HDAC inhibitors. Compared to the control group, poly(I:C) by itself slightly increased LL-37 expression. Importantly, expression of LL-37 in the presence of poly(I:C) is further increased to 19-fold (p < 0.01) at increasing concentrations of TSA (Figure 1A). This increase expression induced by TSA seems a direct effect of TSA as it is also observed in the absence of poly(I:C) as seen in Figure 1B.


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)

Real-time polymerase chain reaction analysis of expression of LL-37 in H292 cells in response to poly(I:C) with or without TSA. (A): The mRNA expression of LL-37 at different concentration of TSA in response to the poly(I:C). (B): Cells were stimulated with different concentration of poly(I:C) for 24 h in the presence or absence of TSA(200 nM). (C): The effect of SB on the LL37 gene expression. *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 1: Real-time polymerase chain reaction analysis of expression of LL-37 in H292 cells in response to poly(I:C) with or without TSA. (A): The mRNA expression of LL-37 at different concentration of TSA in response to the poly(I:C). (B): Cells were stimulated with different concentration of poly(I:C) for 24 h in the presence or absence of TSA(200 nM). (C): The effect of SB on the LL37 gene expression. *p<0.05 vs control. Values represent the mean±SD of three independent experiments.
Mentions: Antibacterial peptides are an integral part of the epithelial defence barrier that provides immediate protection against infection. To characterize the role of epigenetics in the expression of human cathelicidin, we assessed LL-37 expression with or without of HDAC inhibitors. Compared to the control group, poly(I:C) by itself slightly increased LL-37 expression. Importantly, expression of LL-37 in the presence of poly(I:C) is further increased to 19-fold (p < 0.01) at increasing concentrations of TSA (Figure 1A). This increase expression induced by TSA seems a direct effect of TSA as it is also observed in the absence of poly(I:C) as seen in Figure 1B.

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.


Related in: MedlinePlus