Tuberc Respir Dis.  2015 Apr;78(2):99-105. 10.4046/trd.2015.78.2.99.

Regulation of CYP1A1 and Inflammatory Cytokine by NCOA7 Isoform 4 in Response to Dioxin Induced Airway Inflammation

• Cho SH
• Park SY
• Lee EJ
• Cho YH
• Park HS
• Hong SH
• Kim WJ

• KMID: 2320601
• DOI: http://doi.org/10.4046/trd.2015.78.2.99

Abstract

BACKGROUND
Aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, binds to a wide variety of synthetic and naturally occurring compounds. AhR is involved in the regulation of inflammatory response during acute and chronic respiratory diseases. We investigated whether nuclear receptor coactivator 7 (NCOA7) could regulate transcriptional levels of AhR target genes and inflammatory cytokines in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treated human bronchial epithelial cells. This study was based on our previous study that NCOA7 was differentially expressed between normal and chronic obstructive pulmonary disease lung tissues.
METHODS
BEAS-2B and A549 cells grown under serum-free conditions were treated with or without TCDD (0.15 nM and 6.5 nM) for 24 hours after transfection of pCMV-NCOA7 isoform 4. Expression levels of cytochrome P4501A1 (CYP1A1), IL-6, and IL-8 were measured by quantitative real-time polymerase chain reaction.
RESULTS
The transcriptional activities of CYP1A1 and inflammatory cytokines were strongly induced by TCDD treatment in both BEAS-2B and A549 cell lines. The NCOA7 isoform 4 oppositely regulated the transcriptional activities of CYP1A1 and inflammatory cytokines between BEAS-2B and A549 cell lines.
CONCLUSION
Our results suggest that NCOA7 could act as a regulator in the TCDD-AhR signaling pathway with dual roles in normal and abnormal physiological conditions.

Keyword

Receptors, Aryl Hydrocarbon; Pulmonary Disease, Chronic Obstructive; Dioxins; NCOA7 Protein, Human

MeSH Terms

Cell Line
Cytochrome P-450 CYP1A1*
Cytochromes
Cytokines
Dioxins
Epithelial Cells
Humans
Inflammation*
Interleukin-6
Interleukin-8
Lung
Pulmonary Disease, Chronic Obstructive
Real-Time Polymerase Chain Reaction
Receptors, Aryl Hydrocarbon
Tetrachlorodibenzodioxin
Transcription Factors
Transfection
Cytochrome P-450 CYP1A1
Cytochromes
Cytokines
Dioxins
Interleukin-6
Interleukin-8
Receptors, Aryl Hydrocarbon
Tetrachlorodibenzodioxin
Transcription Factors

Figure

• 

  Figure 1 Human nuclear receptor coactivator 7 isoform expression based on RNA-sequencing. Isoforms expression in normal control (NC) and chronic obstructive pulmonary disease (COPD) human lung tissues. FPKM fold change was the ratio of average FPKM between COPD and NC.

• 

  Figure 2 Effect of overexpression of nuclear receptor coactivator 7 (NCOA7) isoform 4 on cytochrome P4501A1 (CYP1A1) mRNA expression. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-induced expression of CYP1A1 mRNA in BEAS-2B (A) and A549 (B) cell cultures. Cells were transfected with mock control vector or the NCOA7 isoform 4 for 24 hours prior to the addition of TCDD (0.15 nM and 0.65 nM) for 24 hours. Bars represent mean±SD. *p<0.05 indicating statistical significance between the mock control- and NCOA7 isoform 4- transfected cells.

• 

  Figure 3 Effect of overexpression of nuclear receptor coactivator 7 (NCOA7) isoform 4 on pro-inflammatory cytokines mRNA expression. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-induced expression of interleukin (IL)-8 and IL-6 mRNA in BEAS-2B (A, C) and A549 (B, D) cell cultures. Cells were transfected with a mock control vector or the NCOA7 isoform 4 for 24 hours prior to addition of TCDD (0.15 nM and 0.65 nM) for 24 hours. Bars represent mean±SD. *p<0.05 indicating statistical significance between the mock control- and NCOA7 isoform 4-transfected cells.

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