title: C/EBP homologous protein promotes NSAID-activated gene 1-linked pro-inflammatory signals and enterocyte invasion by enteropathogenic Escherichia coli.
abstract: 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.
authors: Laboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Medical Research Institute, Pusan National University School of Medicine, Yangsan, 50612, South Korea.
authors: Seong-Hwan
authors: SH
authors: Park
authors: Laboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Medical Research Institute, Pusan National University School of Medicine, Yangsan, 50612, South Korea.
authors: Mira
authors: M
authors: Yu
authors: Laboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Medical Research Institute, Pusan National University School of Medicine, Yangsan, 50612, South Korea.
authors: Juil
authors: J
authors: Kim
authors: Laboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Medical Research Institute, Pusan National University School of Medicine, Yangsan, 50612, South Korea; Immunoregulatory Therapeutics Group in Brain Busan 21 Project, Busan, 46241, South Korea. Electronic address: moon@pnu.edu.
authors: Yuseok
authors: Y
authors: Moon
mesh_terms: D002478:Cells, Cultured; D004705:Endocytosis; D020895:Enterocytes / Q000382:microbiology*; D054308:Enteropathogenic Escherichia coli / Q000472:pathogenicity*; D055436:Growth Differentiation Factor 15 / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction; D051742:Transcription Factor CHOP / Q000378:metabolism*
chemical_list: C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D051742:Transcription Factor CHOP
keywords: C/EBP homologous protein (CHOP); Enteropathogenic Escherichia coli (EPEC); NSAID-activated gene 1 (NAG-1); Nuclear factor kappa B (NF-κB)