Activation of the transcription factor NF-{kappa}B by Campylobacter jejuni

Division of Food Sciences, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK 1 Division of Gastroenterology, University Hospital Nottingham, Queen’s Medical Centre, Nottingham NG7 2UH, UK 2 Author for correspondence: Kenneth H. Mellits. Tel: +44 115 95 16161. Fax: +44 115 95 16162. e-mail: ken.mellits{at}nottingham.ac.uk Campylobacter jejuni is a food-borne pathogen responsible for infectious enterocolitis. The early-response transcription factor NF- B triggers the expression of genes associated with cellular immune and inflammatory responses. Co-incubation of HeLa cells with viable C. jejuni leads to the activation of the transcription factor NF- B as determined by specific induction of a cellular luciferase-based reporter. Boiled cell-free extracts of C. jejuni are also potent dose-dependent stimulators of NF- B-dependent transcription, the levels of which can reach up to 1000-fold as compared with independent controls. Using both cultured HeLa cells and human colonic epithelial (HCA-7) cells, the activation of NF- B by C. jejuni boiled extract has been monitored through the degradation of IKB and DNA binding of the nuclear translocated p50/p65 heterodimer of NF- B. These events are co-ordinated with elaboration of the pro-inflammatory cytokine interleukin-8. Fractionation of the boiled C. jejuni extract suggests that the majority of the bioactive component has a molecular mass of 3 kDa or less, which is insensitive to proteinase K treatment. Keywords: transcription, innate immunity, interleukin-8, inflammation, food safety Abbreviations: BCE, boiled-cell extract; EMS, electrophoretic mobility shift; IL, interleukin; LOS, lipo-oligosaccharide; TNF- ; tumour necrosis factor-