The pattern recognition receptor Nod1 activates CCAAT/enhancer binding protein beta signalling in lung epithelial cells.
The innate immune receptor nucleotide-binding oligomerisation domain protein 1 (Nod1) recognises peptidoglycan containing meso-diaminopimelic acid found in all Gram-negative and some Gram-positive bacteria. Nod1 has been shown to activate nuclear factor (NF)-kappaB. The aim of the present study was to examine the expression of Nod1 in the lung, particularly in lung epithelial cells, and to investigate the activation of CCAAT/enhancer binding protein (C/EBP) transcription factors downstream of the Nod1 receptor in these cells. The expression of Nod1 in mouse lung was examined using immunohistochemistry. A tissue array was used to determine the expression pattern in the human lung. Signalling downstream of Nod1 was examined in the human lung epithelial cell type, BEAS-2B, by electrophoretic mobility shift assay and reporter gene activation. Nod1 expression was seen in various cell types in the lung, including epithelial cells. Activation of Nod1 in these cells resulted in modest activation of NF-kappaB, together with strong activation of the C/EBP transcription factors, particularly C/EBPbeta. This activation appears to be independent of de novo protein synthesis. The present study showed that nucleotide-binding oligomerisation domain protein 1 is expressed in lung epithelial cells. The results demonstrate a novel pathway downstream of the nucleotide-binding oligomerisation domain protein 1 receptor in these cells and suggest that C/EBPbeta may play a role in immune responses to meso-diaminopimelic acid-containing bacteria in the lung.
Department of Medicine-Solna, Division for Respiratory Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden. J.L.Barton@leeds.ac.uk
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D000818:Animals; D015153:Blotting, Western; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D002478:Cells, Cultured; D024202:Electrophoretic Mobility Shift Assay; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053474:Nod1 Signaling Adaptor Protein / Q000502:physiology*; D015398:Signal Transduction; D014162:Transfection
D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta; D053474:Nod1 Signaling Adaptor Protein