CEBPD modulates the airway smooth muscle transcriptomic response to glucocorticoids

Area of Science:

• Cellular and Molecular Biology
• Immunology
• Respiratory Medicine

Background:

• CCAAT/Enhancer Binding Protein D (CEBPD) is a glucocorticoid-responsive transcription factor involved in inflammatory responses.
• CEBPD expression in airway smooth muscle (ASM) increases with glucocorticoid exposure, relevant to asthma.
• This study investigates CEBPD's role in glucocorticoid-induced transcriptomic changes in ASM and its impact on asthma-related function.

Purpose of the Study:

• To characterize CEBPD-mediated transcriptomic responses in ASM cells following glucocorticoid exposure.
• To determine the impact of CEBPD knockdown on gene expression and asthma-related ASM function.
• To elucidate the specific signaling pathways modulated by CEBPD in response to glucocorticoids and TNFα.

Main Methods:

• Primary ASM cells from multiple donors were utilized.
• Cells were transfected with CEBPD or non-targeting siRNA.
• Gene expression was analyzed using RNA-Seq after exposure to vehicle, budesonide, TNFα, or a combination, with and without CEBPD knockdown.

Main Results:

• CEBPD knockdown significantly altered the expression of 3037 genes under various exposure conditions.
• Weighted gene co-expression analysis identified gene sets correlated with CEBPD knockdown and/or TNFα exposure.
• CEBPD knockdown attenuated budesonide-induced IL-6 receptor expression and reduced IL-6-induced STAT3 phosphorylation in ASM.

Conclusions:

• CEBPD plays a significant role in modulating glucocorticoid responses within ASM.
• CEBPD's influence on glucocorticoid responses is partly mediated through the regulation of IL-6 receptor signaling.
• These findings highlight CEBPD as a potential therapeutic target for asthma management.