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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.


ELISA analysis of IL-6 expression in the airway epithelial cells. The effect of HDAC inhibitors on IL-6 production in the NCI-H292 cells (A) and the primary nasal epithelial cells (B) in response to poly(I:C) stimulation. Cells were pretreated respectively with TSA (200 nM) or SB(4 mM) for 2 h prior to the poly(I:C) (20 ug/ml) stimulation for 24 h. IL-6 production in cell supernatant was analyzed using ELISA. *p<0.05 vs control. Values represent the mean±SD of three independent experiments.
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Figure 4: ELISA analysis of IL-6 expression in the airway epithelial cells. The effect of HDAC inhibitors on IL-6 production in the NCI-H292 cells (A) and the primary nasal epithelial cells (B) in response to poly(I:C) stimulation. Cells were pretreated respectively with TSA (200 nM) or SB(4 mM) for 2 h prior to the poly(I:C) (20 ug/ml) stimulation for 24 h. IL-6 production in cell supernatant was analyzed using ELISA. *p<0.05 vs control. Values represent the mean±SD of three independent experiments.

Mentions: TSA was recently reported to inhibit IL-6 production from monocytes and macrophages [10]. To determine if HDAC inhibitors could also suppress IL-6 production in the airway epithelium, we treated the H292 cells and primary nasal epithelial cells with HDAC inhibitors for 2 h prior to poly(I:C) stimulation. In our experiment, poly(I:C) stimulation for 24 h significantly increased IL-6 protein expression level in both of the airway epithelial cells. Interestingly, we found that pre-incubation with HDAC inhibitors inhibited the IL-6 protein expression in H292 cells (Figure 4A). In the primary nasal epithelial cells, only SB significantly induced IL-6 expression (Figure 4B).


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)

ELISA analysis of IL-6 expression in the airway epithelial cells. The effect of HDAC inhibitors on IL-6 production in the NCI-H292 cells (A) and the primary nasal epithelial cells (B) in response to poly(I:C) stimulation. Cells were pretreated respectively with TSA (200 nM) or SB(4 mM) for 2 h prior to the poly(I:C) (20 ug/ml) stimulation for 24 h. IL-6 production in cell supernatant was analyzed using ELISA. *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 4: ELISA analysis of IL-6 expression in the airway epithelial cells. The effect of HDAC inhibitors on IL-6 production in the NCI-H292 cells (A) and the primary nasal epithelial cells (B) in response to poly(I:C) stimulation. Cells were pretreated respectively with TSA (200 nM) or SB(4 mM) for 2 h prior to the poly(I:C) (20 ug/ml) stimulation for 24 h. IL-6 production in cell supernatant was analyzed using ELISA. *p<0.05 vs control. Values represent the mean±SD of three independent experiments.
Mentions: TSA was recently reported to inhibit IL-6 production from monocytes and macrophages [10]. To determine if HDAC inhibitors could also suppress IL-6 production in the airway epithelium, we treated the H292 cells and primary nasal epithelial cells with HDAC inhibitors for 2 h prior to poly(I:C) stimulation. In our experiment, poly(I:C) stimulation for 24 h significantly increased IL-6 protein expression level in both of the airway epithelial cells. Interestingly, we found that pre-incubation with HDAC inhibitors inhibited the IL-6 protein expression in H292 cells (Figure 4A). In the primary nasal epithelial cells, only SB significantly induced IL-6 expression (Figure 4B).

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.