The pattern recognition receptor Nod1 activates CCAAT/enhancer binding protein beta signalling in lung epithelial...

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• The innate immune receptor nucleotide-binding oligomerisation domain protein 1 (Nod1) recognizes bacterial peptidoglycans.
• Nod1 signaling is known to activate nuclear factor (NF)-kappaB.
• The role of Nod1 and its downstream signaling in lung epithelial cells remains to be fully elucidated.

Purpose of the Study:

• To investigate the expression of Nod1 in lung epithelial cells.
• To explore the activation of CCAAT/enhancer binding protein (C/EBP) transcription factors downstream of Nod1 in these cells.
• To understand Nod1's contribution to lung immune responses.

Main Methods:

• Immunohistochemistry was used to examine Nod1 expression in mouse and human lung tissues.
• A tissue array was employed for human lung expression patterns.
• Electrophoretic mobility shift assay and reporter gene activation were used in BEAS-2B cells to study Nod1 signaling.

Main Results:

• Nod1 expression was detected in various lung cell types, including epithelial cells.
• Activation of Nod1 led to modest NF-kappaB activation and strong activation of C/EBP transcription factors, especially C/EBPbeta.
• C/EBP activation downstream of Nod1 appeared independent of de novo protein synthesis.

Conclusions:

• Nucleotide-binding oligomerisation domain protein 1 is expressed in lung epithelial cells.
• A novel signaling pathway involving Nod1 and C/EBP transcription factors was identified in lung epithelial cells.
• C/EBPbeta may play a significant role in the lung's immune response to bacteria containing meso-diaminopimelic acid.