Immune Netw.  2013 Apr;13(2):75-79. 10.4110/in.2013.13.2.75.

IL-4 and HDAC Inhibitors Suppress Cyclooxygenase-2 Expression in Human Follicular Dendritic Cells

• Cho W
• Hong SH
• Choe J

• KMID: 1431929
• DOI: http://doi.org/10.4110/in.2013.13.2.75

Abstract

Evidence for immunoregulatory roles of prostaglandins (PGs) is accumulating. Since our observation of PG production by human follicular dendritic cells (FDCs), we investigated the regulatory mechanism of PG production in FDC and attempted to understand the functions of released PGs in the responses of adjacent lymphocytes. Here, using FDC-like cells, HK cells, we analyzed protein expression alterations in cyclooxygenase-2 (COX-2) in the presence of IL-4 or histone deacetylase (HDAC) inhibitors. Both IL-4 and HDAC inhibitors suppressed COX-2 expression in dose-dependent manners. Their effect was specific to COX-2 and did not reach to COX-1 expression. Interestingly, HDAC inhibitors gave rise to an opposing effect on COX-2 expression in peripheral blood monocytes. Our results suggest that IL-4 may regulate COX-2 expression in FDCs by affecting chromatin remodeling and provide insight into the role of cellular interactions between T cells and FDC during the GC reaction. Given the growing interests in wide-spectrum HDAC inhibitors, the differential results on COX-2 expression in HK cells and monocytes raise cautions on their clinical use.

Keyword

Human; Stromal cells; Lipid mediator; Histone

MeSH Terms

Chromatin Assembly and Disassembly
Cyclooxygenase 2
Dendritic Cells, Follicular
Histone Deacetylase Inhibitors
Histone Deacetylases
Histones
Humans
Interleukin-4
Lymphocytes
Monocytes
Prostaglandins
Stromal Cells
T-Lymphocytes
Cyclooxygenase 2
Histone Deacetylase Inhibitors
Histone Deacetylases
Histones
Interleukin-4
Prostaglandins

Figure

• 

  Figure 1 IL-4 broadly inhibits COX-2 protein expression induced by various stimuli in HK cells. (A) HK cells (1×105 cells) were cultured in the presence or absence of IL-4 (100 U/ml) for 24 h and incubated further with additional presence of TGF-β (1 ng/ml), LPS (1 µg/ml), IFN-γ (1 ng/ml), or TNF-α (0.5 ng/ml) for 8 h. The expression levels of COX proteins were measured by immunoblotting. β-actin was used to control equal loading of samples. (B) Quantification of immunoblots was performed to show means±SEM of two independent experiments. Asterisks indicate significant differences (*p<0.05, **p<0.01, ***p<0.001).

• 

  Figure 2 HDAC inhibitors attenuate LPS-induced COX-2 expression in HK cells, but not in monocytes. HK cells (1×105 cells) (A) and peripheral blood monocytes (1×106 cells) (C) were cultured in the presence of trichostatin A (0.1~100 nM) or sodium butyrate (0.001~1 mM) for 30 min and incubated further with the additional presence of LPS (1 µg/ml) for 8 h. The expression levels of COX proteins were measured by immunoblotting. Quantification of immunoblots of HK cells (B) and monocytes (D) was performed to show means±SEM of two independent experiments. Asterisks indicate significant differences (*p<0.05, **p<0.01)

• 

  Figure 3 HDAC inhibitor does not affect viability of HK cells. HK cells (1×104 cells) were incubated in the presence of sodium butyrate (0.008~1 mM) for 30 min and then with the additional presence of LPS (1 µg/ml) for 24 h. The viability of HK cells was determined by a colorimetric assay using CCK-8 reagents as described in MATERIALS AND METHODS.

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