ASC, which is composed of a PYD and a CARD, is up-regulated by inflammation and apoptosis in human neutrophils.
ASC is an adaptor protein that is composed of two protein-protein interaction domains, a PYRIN domain (PYD), and a caspase-recruitment domain (CARD). Recently, ASC was identified as a binding partner of pyrin, which is the product of MEFV, a gene causing familial Mediterranean fever (FMF). Mutations in MEFV result in defects in control of neutrophil-mediated inflammation. Thus we focused on the expression of ASC in neutrophils. Immunohistochemical study showed that ASC is increased in neutrophils in severe inflammatory sites of gangrenous appendicitis. We, then, tested whether proinflammatory mediators induce ASC using peripheral blood neutrophils in vitro. ASC expression was transiently up-regulated by IL-1alpha, IL-1beta, IFN-alpha, IFN-gamma, TNFalpha, and LPS. ASC was also increased by incubation with either anti-Fas antibody or recombinant soluble Fas ligand. The Fas-mediated induction of ASC was inhibited by a general caspase inhibitor, z-VAD-fmk, and an immunocytochemical study showed that ASC was increased in neutrophils exhibiting characteristic phenotypes for apoptosis. These findings suggest that up-regulation of ASC is closely associated with inflammation and apoptosis in neutrophils.
Shiohara
Masaaki
M
Department of Pediatrics, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan.
Taniguchi
Shun'ichiro
S
Masumoto
Junya
J
Yasui
Kozo
K
Koike
Kenichi
K
Komiyama
Atsushi
A
Sagara
Junji
J
D017209:Apoptosis; D001665:Binding Sites; D053468:CARD Signaling Adaptor Proteins; D002455:Cell Division; D003598:Cytoskeletal Proteins; D006801:Humans; D007249:Inflammation; D016898:Interferon-alpha / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009154:Mutation; D009504:Neutrophils / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000502:physiology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins; D016898:Interferon-alpha; D007375:Interleukin-1; D008070:Lipopolysaccharides; C402202:PYCARD protein, human; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma