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The pattern recognition receptor Nod1 activates CCAAT/enhancer binding protein ß signalling in lung epithelial cells

¹ Dept of Medicine-Solna, Division for Respiratory Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, and, ⁴ Discovery Medicine, Medical Science, Astra Zeneca R&D, Lund, Sweden. ² Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK. ³ Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA.

CORRESPONDENCE: J. L. Barton, Leeds Institute of Molecular Medicine, Level 6, Wellcome Trust Brenner Building, St James's University Hospital, Beckett Street, Leeds LS9 7TF, UK. Fax: 44 1133438502. E-mail: J.L.Barton{at}leeds.ac.uk

Keywords: CCAAT/enhancer binding protein, innate immune system, intracellular signalling, lung epithelium, nucleotide-binding oligomerisation domain protein 1 receptor, transcription factors

Received: November 5, 2006
Accepted May 29, 2007

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)-B. 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-B, together with strong activation of the C/EBP transcription factors, particularly C/EBPß. 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/EBPß may play a role in immune responses to meso-diaminopimelic acid-containing bacteria in the lung.