STAT1-mediated induction of Ly6c-expressing macrophages are involved in the pathogenesis of an acute colitis model

Autor: Shuhei Kii, Hidemitsu Kitamura, Shinichi Hashimoto, Kazuho Ikeo, Nobuki Ichikawa, Tadashi Yoshida, Shigenori Homma, Mishie Tanino, Akinobu Taketomi
Rok vydání: 2022
Předmět:
Zdroj: Inflammation Research. 71:1079-1094
ISSN: 1420-908X
1023-3830
DOI: 10.1007/s00011-022-01620-z
Popis: 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.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.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.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.
Databáze: OpenAIRE
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