C/EBP homologous protein promotes NSAID-activated gene 1-linked pro-inflammatory signals and enterocyte invasion by enteropathogenic Escherichia coli

NSAID-activated Gene 1 (NAG-1) is a prognostic indicator of chronic inflammatory diseases and aggressive tumors. Among the stress sentinels in response to infection by enteropathogenic Escherichia coli (EPEC) or other pathogenic E. coli, C/EBP homologous protein (CHOP), a representative stress-regulated transcription factor, was prominently increased and assessed for its involvement in NAG-1-mediated pathogenic cellular responses. NAG-1 expression was transcriptionally upregulated by CHOP, which promoted chemokine production through sustained NF-κB activation. Mechanistically, NF-κB activation by NAG-1 was due to TGFβ-activated kinase 1 (TAK-1)-mediated pathway rather than SMAD-associated signals. Moreover, CHOP and subsequent TAK-1-linked signals were also involved in bacterial invasion into human cells. Therefore, CHOP as an infection-induced sentinel played crucial roles in induction of NAG-1 and subsequent prolonged activation of pro-inflammatory responses to EPEC infection or related chronic pathogenic states.