| Title: | STAT1-mediated induction of Ly6c-expressing macrophages are involved in the pathogenesis of an acute colitis model |
| Authors: | Kii, Shuhei Browse this author |
| Kitamura, Hidemitsu Browse this author →KAKEN DB |
| Hashimoto, Shinichi Browse this author |
| Ikeo, Kazuho Browse this author |
| Ichikawa, Nobuki Browse this author |
| Yoshida, Tadashi Browse this author |
| Homma, Shigenori Browse this author →KAKEN DB |
| Tanino, Mishie Browse this author |
| Taketomi, Akinobu Browse this author →KAKEN DB |
| Keywords: | Signal transducer and activator of transcription 1 |
| CCR2 |
| Ly6c |
| Macrophages |
| Inflammatory bowel disease |
| Issue Date: | 1-Sep-2022 |
| Journal Title: | Inflammation Research |
| Volume: | 71 |
| Issue: | 9 |
| Start Page: | 1079 |
| End Page: | 1094 |
| Publisher DOI: | 10.1007/s00011-022-01620-z |
| Abstract: | Background
The development of inflammatory bowel diseases is thought to be multifactorial, but the exact steps in pathogenesis are poorly understood. In this study, we investigated involvement of the activation of STAT1 signal pathway in the pathogenesis of an acute colitis model.
Methods
A dextran sulfate sodium-induced acute colitis model was established by using wild-type C57BL/6 mice and STAT1-deficient mice. Disease indicators such as body weight loss and clinical score, induction of cytokines, chemokines, and inflammatory cells were evaluated in the acute colitis model.
Results
Disease state was significantly improved in the acute colitis model using STAT1-deficient mice compared with wild-type mice. The induction of Ly6c-highly expressing cells in colorectal tissues was attenuated in STAT1-deficient mice. IL-6, CCL2, and CCR2 gene expressions in Ly6c-highly expressing cells accumulated in the inflamed colon tissues and were significantly higher than in Ly6c-intermediate-expressing cells, whereas TNF-α and IFN-α/β gene expression was higher in Ly6c-intermediate-expressing cells. Blockade of CCR2-mediated signaling significantly reduced the disease state in the acute colitis model.
Conclusions
Two different types of Ly6c-expressing macrophages are induced in the inflamed tissues through the IFN-α/β-STAT1-mediated CCL2/CCR2 cascade and this is associated with the pathogenesis such as onset, exacerbation, and subsequent chronicity of acute colitis. |
| Rights: | This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1007/s00011-022-01620-z |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/90332 |
| Appears in Collections: | 遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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