title: Signal-transducing adaptor protein-2 regulates macrophage migration into inflammatory sites during dextran sodium sulfate induced colitis.
abstract: Signal-transducing adaptor protein-2 (STAP-2) was cloned as a c-fms/M-CSF receptor interacting protein. STAP-2 is an adaptor protein carrying pleckstrin homology and Src homology 2 like domains, as well as a YXXQ motif. STAP-2 has been indicated to have an ability to bind and modulate a variety of signaling and transcriptional molecules. Especially, our previous in vitro studies showed that STAP-2 is crucial for immune and/or inflammatory responses. Here, we have investigated the role of STAP-2 in intestinal inflammation in vivo. The disruption of STAP-2 attenuates dextran sodium sulfate induced colitis via inhibition of macrophage recruitment. To study whether hematopoietic or epithelial cell derived STAP-2 is required for this phenomenon, we generated BM chimeric mice. STAP-2-deficient macrophages impair the ability of CXCL12-induced migration. Intriguingly, STAP-2 also regulates production of proinflammatory chemokines and cytokines such as CXCL1 and TNF-α from intestinal epithelial cells. Therefore, STAP-2 has a potential to regulate plural molecular events during pathological inflammatory responses. Furthermore, our findings not only indicate that STAP-2 is important in regulating intestinal inflammation, but also provide new insights toward the development of novel therapeutic approaches.
authors.affiliation: Department of Hematology and Oncology, Osaka University Graduate School of medicine, Osaka, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Fujita
authors.forename: Kenji
authors.initials: K
authors.lastname: Oritani
authors.forename: Michiko
authors.initials: M
authors.lastname: Ichii
authors.forename: Takafumi
authors.initials: T
authors.lastname: Yokota
authors.forename: Norimitsu
authors.initials: N
authors.lastname: Saitoh
authors.forename: Daisuke
authors.initials: D
authors.lastname: Okuzaki
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sekine
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kon
authors.forename: Ryuta
authors.initials: R
authors.lastname: Muromoto
authors.forename: Kodai
authors.initials: K
authors.lastname: Saitoh
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsuda
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Kanakura
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology*; D064591:Allografts; D000818:Animals; D016026:Bone Marrow Transplantation; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D054360:Chemokine CXCL1 / Q000235:genetics / Q000276:immunology; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity*; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D018183:Transplantation Chimera / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; C523144:STAP2 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D016264:Dextran Sulfate
keywords: Chemokine; Colitis; Dextran sodium sulfate (DSS); Macrophages; Signal-transducing adaptor protein-2 (STAP-2)