title: Rac1 regulates the NLRP3 inflammasome which mediates IL-1beta production in Chlamydophila pneumoniae infected human mononuclear cells.
abstract: Chlamydophila pneumoniae causes acute respiratory tract infections and has been associated with development of asthma and atherosclerosis. The production of IL-1β, a key mediator of acute and chronic inflammation, is regulated on a transcriptional level and additionally on a posttranslational level by inflammasomes. In the present study we show that C. pneumoniae-infected human mononuclear cells produce IL-1β protein depending on an inflammasome consisting of NLRP3, the adapter protein ASC and caspase-1. We further found that the small GTPase Rac1 is activated in C. pneumoniae-infected cells. Importantly, studies with specific inhibitors as well as siRNA show that Rac1 regulates inflammasome activation in C. pneumoniae-infected cells. In conclusion, C. pneumoniae infection of mononuclear cells stimulates IL-1β production dependent on a NLRP3 inflammasome-mediated processing of proIL-1β which is controlled by Rac1.
authors.affiliation: Department of Internal Medicine, Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Eitel
authors.forename: Karolin
authors.initials: K
authors.lastname: Meixenberger
authors.forename: Claudia
authors.initials: C
authors.lastname: van Laak
authors.forename: Christine
authors.initials: C
authors.lastname: Orlovski
authors.forename: Andreas
authors.initials: A
authors.lastname: Hocke
authors.forename: Bernd
authors.initials: B
authors.lastname: Schmeck
authors.forename: Stefan
authors.initials: S
authors.lastname: Hippenstiel
authors.forename: Philippe Dje
authors.initials: PD
authors.lastname: N'Guessan
authors.forename: Norbert
authors.initials: N
authors.lastname: Suttorp
authors.forename: Bastian
authors.initials: B
authors.lastname: Opitz
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D016993:Chlamydophila pneumoniae / Q000276:immunology* / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D016133:Polymerase Chain Reaction; D034622:RNA Interference; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D020830:rac1 GTP-Binding Protein