title: Toxin-induced calcium oscillations: a novel strategy to affect gene regulation in target cells.
abstract: Although the mucosal linings continuously are exposed to microbes, the microbes rarely induce disease. This is because mucosal surfaces are protected by a first line of host defence termed the innate immunity system. The innate immune response is an outcome of the complex interplay between microbes and host target cells, and leads to the activation of inflammatory processes. Although inflammation is essential for clearing out infectious agents, it can also be harmful to the host and is therefore subjected to control at multiple levels. We recently discovered that alpha-haemolysin, a toxin secreted by uropathogenic E. coli induces constant, low-frequency Ca2+ oscillations in renal epithelial cells (Uhlén et al., Nature 405, 694-696 (2000)). Ca2+ oscillation at a specific periodicity of 12 min was found to affect gene expression in target epithelial cells, as the proinflammatory cytokine IL-6 and chemokine IL-8 were specifically induced by alpha-haemolysin-induced Ca2+ oscillations. This demonstrates a novel feature of bacterial toxin effects on host target cells: as inducers of second messenger responses which fine-tune gene expression in target epithelial cells into pathways leading to e. g. a pro-inflammatory response.
authors.affiliation: Microbiology and Tumorbiology Center, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Söderblom
authors.forename: Asa
authors.initials: A
authors.lastname: Laestadius
authors.forename: Camilla
authors.initials: C
authors.lastname: Oxhamre
authors.forename: Anita
authors.initials: A
authors.lastname: Aperia
authors.forename: Agneta
authors.initials: A
authors.lastname: Richter-Dahlfors
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology; D004926:Escherichia coli / Q000378:metabolism / Q000472:pathogenicity*; D005786:Gene Expression Regulation; D006460:Hemolysin Proteins / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007668:Kidney
chemical_list: D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D015850:Interleukin-6; D016209:Interleukin-8; D002118:Calcium