title: IL-19 is involved in the pathogenesis of endotoxic shock.
abstract: IL-19, a proinflammatory cytokine, belongs to the IL-10 family. IL-19 is induced in systemic inflammatory response syndrome, but its pathophysiological function in sepsis is unclear. Our aim was to determine the roles of IL-19 in endotoxin-induced tissue damage in vivo and in vitro. We examined serum levels of IL-19 in sepsis patients and healthy volunteers, determined the in vitro effects of IL-19 on lung epithelial cells, liver cells, and neutrophils, and analyzed the tissue expression of IL-19 and its receptors in murine endotoxic shock. Electroporation-mediated gene transfer of mouse IL-19-soluble receptor plasmid DNA was used to determine the effects of IL-19 depletion in preventing endotoxic shock-induced tissue damage in mice. We found that serum levels of IL-19 were higher in patients than in healthy volunteers (n = 28, P = 0.001). IL-19 induced apoptosis in lung epithelial cells and reactive oxygen species production in liver cells in vitro. IL-19 also promoted neutrophil chemotaxis, reduced neutrophil apoptosis, and induced the production of proinflammatory cytokines and chemokines (IL-1[beta], IL-6, IL-8, CCL5, and CXCL9) in lung epithelial cells. In LPS-challenged mice, transcripts of IL-19 and its receptors were up-regulated in heart, lung, liver, and kidney tissue. Neutrophil infiltration in lung and liver tissue, and serum levels of alanine transaminase and aspartate transaminase, were lower in mice electroporated with IL-19-soluble receptor plasmid DNA before LPS treatment compared with control mice. These results suggest that up-regulated IL-19 may be involved in lung and liver tissue injury in murine endotoxic shock.
authors.affiliation: Institute of Biopharmaceutical Sciences, Medical College, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chung-Hsi
authors.initials: CH
authors.lastname: Hsing
authors.forename: Chiau-Juon
authors.initials: CJ
authors.lastname: Chiu
authors.forename: Lih-Yun
authors.initials: LY
authors.lastname: Chang
authors.forename: Chuan-Chih
authors.initials: CC
authors.lastname: Hsu
authors.forename: Ming-Shi
authors.initials: MS
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D016022:Case-Control Studies; D002460:Cell Line; D018925:Chemokines / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics / Q000494:pharmacology; D007378:Interleukins / Q000097:blood* / Q000235:genetics; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D017382:Reactive Oxygen Species / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics; D018805:Sepsis / Q000097:blood / Q000276:immunology; D012772:Shock, Septic / Q000097:blood / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018925:Chemokines; D017931:DNA Primers; C421250:IL19 protein, human; C498891:Il19 protein, mouse; D007378:Interleukins; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D018123:Receptors, Interleukin; D016753:Interleukin-10