Divergent signalling pathways regulate lipopolysaccharide-induced eRNA expression in human monocytic THP1 cells

Area of Science:

• Molecular Biology
• Immunology
• Genetics

Background:

• Non-coding RNAs transcribed from enhancers, known as enhancer RNAs (eRNAs), are emerging as key regulators of enhancer activity and gene expression.
• Understanding the role of eRNAs in cellular responses, particularly in the innate immune system, is crucial for deciphering complex gene regulatory networks.

Purpose of the Study:

• To characterize the expression of specific enhancer RNAs (eRNAs) in human monocytic THP1 cells upon innate immune activation.
• To elucidate the intracellular signaling pathways, including NF-κB and mitogen-activated protein kinases (MAPKs), that mediate the induction of these eRNAs by lipopolysaccharide (LPS).

Main Methods:

• Utilized human monocytic THP1 cells as a model system.
• Activated innate immune response using lipopolysaccharide (LPS).
• Characterized the expression of six specific enhancer RNAs (eRNAs) and analyzed the involvement of NF-κB and MAPK signaling pathways (ERK1/2, p38).

Main Results:

• Demonstrated that lipopolysaccharide (LPS) significantly induces the expression of six distinct enhancer RNAs (eRNAs) in THP1 cells.
• Showed that the induction of individual eRNAs is regulated by distinct intracellular signaling cascades.
• Identified the involvement of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinases (MAPKs), specifically extracellular signal-regulated kinases 1/2 (ERK1/2) and p38, in mediating LPS-induced eRNA expression.

Conclusions:

• Enhancer RNAs (eRNAs) are dynamically regulated during the innate immune response.
• Lipopolysaccharide (LPS) triggers the expression of specific eRNAs through divergent signaling pathways involving NF-κB and MAPKs.
• These findings highlight the intricate role of eRNAs in innate immunity and gene regulation.