{
    "abstract": "Indoleamine-2,3-dioxygenase 1 (IDO1) is the rate-limiting enzyme in tryptophan (Trp) catabolism along kynurenine (Kyn) pathway. Increased IDO1 activity has been noticed in patients with sepsis, while IDO1's involvement in sepsis, especially in the initial cytokine storm phase is not yet completely understood. Using the GEO database and clinical samples of sepsis, current study revealed that IDO1-AHR-CYP1A1 axis was significantly upregulated and closely related to cytokine storm in septic patients. With cell models of cytokine storm, it was found that IDO1 promoted cytokine storm and the apoptosis of model cells via AHR-CYP1A1, and IDO1-AHR-CYP1A1 axis correlated classic cytokine storm signal pathway including STAT3, NF-\u03baB/STAT1, JNK/p38. With mouse models of septic cytokine storm, it was shown that IDO1 inhibitors could block the upregulated IDO1-AHR-CYP1A1 axis, reduce the enhanced inflammatory cytokine levels, decrease the phosphorylation of classic cytokine storm signal pathway, rescue organ damage, and increase survival rate. It was also found that IDO1 activation occurred after the increase of inflammatory cytokine levels. Therefore, classic cytokine storm signal pathways, inflammatory cytokines and IDO1-AHR-CYP1A1 axis form a tripartite interaction loop to promote cytokine storm. IDO1 inhibitors were able to block this process.",
    "authors": [
        {
            "affiliation": "State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, MOE Engineering Research Center of Gene Technology, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Songhu Road 2005, Shanghai 200438, China.",
            "firstname": "Yunqiu",
            "initials": "Y",
            "lastname": "Chen"
        },
        {
            "affiliation": "Department of Critical Care Medicine, Children's Hospital of Fudan University, National Children's Medical Center, Fudan University, Wanyuan Road 399, Shanghai 201102, China.",
            "firstname": "Jiayun",
            "initials": "J",
            "lastname": "Ying"
        },
        {
            "affiliation": "State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, MOE Engineering Research Center of Gene Technology, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Songhu Road 2005, Shanghai 200438, China.",
            "firstname": "Zhiyao",
            "initials": "Z",
            "lastname": "Li"
        },
        {
            "affiliation": "State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, MOE Engineering Research Center of Gene Technology, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Songhu Road 2005, Shanghai 200438, China.",
            "firstname": "Zhen Ning Tony",
            "initials": "ZNT",
            "lastname": "He"
        },
        {
            "affiliation": "State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, MOE Engineering Research Center of Gene Technology, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Songhu Road 2005, Shanghai 200438, China.",
            "firstname": "Jiani",
            "initials": "J",
            "lastname": "Zhan"
        },
        {
            "affiliation": "State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, MOE Engineering Research Center of Gene Technology, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Songhu Road 2005, Shanghai 200438, China.",
            "firstname": "Heng",
            "initials": "H",
            "lastname": "Liang"
        },
        {
            "affiliation": "State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, MOE Engineering Research Center of Gene Technology, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Songhu Road 2005, Shanghai 200438, China.",
            "firstname": "Yuying",
            "initials": "Y",
            "lastname": "Liu"
        },
        {
            "affiliation": "State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, MOE Engineering Research Center of Gene Technology, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Songhu Road 2005, Shanghai 200438, China.",
            "firstname": "Yijia",
            "initials": "Y",
            "lastname": "Chen"
        },
        {
            "affiliation": "State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, MOE Engineering Research Center of Gene Technology, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Songhu Road 2005, Shanghai 200438, China.",
            "firstname": "Xuewen",
            "initials": "X",
            "lastname": "Li"
        },
        {
            "affiliation": "Department of Critical Care Medicine, Children's Hospital of Fudan University, National Children's Medical Center, Fudan University, Wanyuan Road 399, Shanghai 201102, China.",
            "firstname": "Ting",
            "initials": "T",
            "lastname": "Zhu"
        },
        {
            "affiliation": "Shanghai Key Lab of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Siping Road 1239, Shanghai 200092, China.",
            "firstname": "Chunxiang",
            "initials": "C",
            "lastname": "Kuang"
        },
        {
            "affiliation": "Department of Critical Care Medicine, Children's Hospital of Fudan University, National Children's Medical Center, Fudan University, Wanyuan Road 399, Shanghai 201102, China; Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Fudan University, Dongan Road 130, Shanghai 200032, China. Electronic address: 13788904150@163.com.",
            "firstname": "Guoping",
            "initials": "G",
            "lastname": "Lu"
        },
        {
            "affiliation": "State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, MOE Engineering Research Center of Gene Technology, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Songhu Road 2005, Shanghai 200438, China. Electronic address: yangqing68@fudan.edu.cn.",
            "firstname": "Qing",
            "initials": "Q",
            "lastname": "Yang"
        }
    ],
    "conclusions": null,
    "copyrights": "Copyright \u00a9 2025. Published by Elsevier Masson SAS.",
    "doi": "10.1016/j.biopha.2025.118054",
    "journal": "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie",
    "keywords": [
        "AHR-CYP1A1",
        "Cytokine storm",
        "IDO1",
        "Inflammatory cytokines",
        "Sepsis"
    ],
    "methods": null,
    "publication_date": "2025-04-18",
    "pubmed_id": "40245547",
    "results": null,
    "title": "IDO1 inhibitors block septic cytokine storm by suppressing the IDO1-AHR-CYP1A1 axis.",
    "xml": "<Element 'PubmedArticle' at 0x788503d92a70>"
}