Campylobacter jejuni activates mitogen-activated protein kinases in Caco-2 cell monolayers and in vitro infected primary human colonic tissue

1 Institute of Comparative Medicine, Sir Henry Wellcome Building, University of Glasgow Faculty of Veterinary Medicine, Bearsden Road, Glasgow G61 1QH, UK 2 Department of Paediatric Surgery, Yorkhill Hospital, Glasgow G3 8SJ, UK Correspondence Paul Everest phe3d{at}udcf.gla.ac.uk The mitogen-activated protein kinases (MAPKs) play a central role in many host signalling pathways. These signalling proteins are known to be involved in host responses against invasive bacteria including generation of chemotactic and inflammatory cytokines. It was hypothesized that Campylobacter jejuni may activate MAPKs, as intestinal infection may induce a clinical and pathological picture of acute colonic inflammation. Infection of Caco-2 cell monolayers (human colonic epithelial cell line) and human colonic tissue with C. jejuni in vitro demonstrated increased MAPK activity for ERK 1/2 (p44/42 MAPK), JNK and p38 MAPKs. Kinase activity and phosphorylated forms were increased in infected Caco-2 cells and human colonic explants, suggesting that these pathways are important in inflammatory responses induced by C. jejuni in man. Abbreviations: ERK, extracellular signal regulated kinase; JNK, c- jun N-terminal kinase; MAPK, mitogen-activated protein kinase; MAPKK or MEK, MAPK kinase; MAPKKK/MEKK, MAPKK/MEK kinase; SAPK, stress-activated protein kinase; TEER, transepithelial electrical resistance; VAIN, variable-atmosphere incubator