Regulation of the ASC expression in response to LPS stimulation is related to IL-8 secretion in the human intestinal mucosa.
Expression of the caspase-activating adaptor ASC was reported to be associated with the production of IL-8, a primary mediator of mucosal inflammation, in vitro. However, the significance of the ASC-mediated IL-8 production in primary tissues has remained poorly understood. Primary intestinal mucosa isolated from surgically resected ileum or colon was incubated with several concentrations of LPS or left untreated. ASC expression was up-regulated at 2 h after stimulation with low doses of LPS (1-10 ng/ml), and was associated with IL-8 secretion, and then was down-regulated later. In contrast, ASC expression remained at the basal level in mucosal tissue treated with a high dose of LPS (1000 ng/ml). Interestingly, in mucosa from several cases of Crohn's disease, ASC was highly expressed without stimulation, and IL-8 was stably secreted with no regulation by LPS. These findings revealed that ASC expression correlates with IL-8 secretion and may play an important role in maintaining mucosal homeostasis.
Masumoto
Junya
J
Department of Pathology, Shinshu University School of Medicine, Matsumoto, Nagano 390-8621, Japan. masumoto@sch.md.shinshu-u.ac.jp
Kobayashi
Hitoshi
H
Nakamura
Takamichi
T
Kaneko
Yasunori
Y
Ota
Hiroyoshi
H
Hasegawa
Mizuho
M
Kobayashi
Yukihiro
Y
Suzuki
Takefumi
T
Matsuda
Kazuyuki
K
Sano
Kenji
K
Katsuyama
Tsutomu
T
Inohara
Naohiro
N
D053468:CARD Signaling Adaptor Proteins; D003424:Crohn Disease / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D046509:Tissue Culture Techniques; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins; D016209:Interleukin-8; D008070:Lipopolysaccharides; C402202:PYCARD protein, human; D014409:Tumor Necrosis Factor-alpha