title: Caspase-1 promotes monocyte-macrophage differentiation by repressing PPARγ.
abstract: Monocyte-to-macrophage differentiation is tightly controlled in vivo, as disruption of the normal differentiation program can lead to diverse disorders. Caspase-1, the first identified member of the caspase family, regulates differentiation in various cell types such as Th17 cells and adipocytes. However, the contribution of caspase-1 in monocyte-macrophage differentiation remains elusive. Here we report that caspase-1 is significantly downregulated in leukemia cells from patients with acute monocytic leukemia. By using the phorbol 12-myristate 13-acetate-induced cell differentiation model, we found that caspase-1 activation was required for the differentiation of human monocytes to macrophages. Further analysis of peroxisome proliferator-activated receptor γ (PPARγ) protein levels revealed that the monocyte-macrophage differentiation program could be divided into two stages. Caspase-1-mediated downregulation of PPARγ was important in the late stage of monocyte-macrophage differentiation; however, PPARγ protein levels had little effect on the early stage differentiation. Accumulation of PPARγ protein by troglitazone treatment potently suppressed the late stage of macrophage differentiation, which might be linked to inhibition of nuclear factor-κB activity. The data provide a plausible mechanistic basis by which caspase-1 promotes the differentiation of macrophages from monocytes.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, China.
authors.forename: Zhiyuan
authors.identifier: 0000-0001-5699-5324
authors.initials: Z
authors.lastname: Niu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, China.
authors.forename: Jiajin
authors.initials: J
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, China.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, China.
authors.forename: Yahong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Hematology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, China.
authors.forename: Bing
authors.identifier: 0000-0002-3597-7861
authors.initials: B
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, China.
authors.forename: Jiahong
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, China.
authors.forename: Pingping
authors.initials: P
authors.lastname: Shen
mesh_terms: D001665:Binding Sites; D020170:Caspase 1 / Q000235:genetics* / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007948:Leukemia, Monocytic, Acute / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics* / Q000276:immunology; D047495:PPAR gamma / Q000235:genetics* / Q000276:immunology; D061251:Primary Cell Culture; D011485:Protein Binding; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology; D000077288:Troglitazone
chemical_list: D002839:Chromans; D007004:Hypoglycemic Agents; D016328:NF-kappa B; D047495:PPAR gamma; D045162:Thiazolidinediones; D020170:Caspase 1; D000077288:Troglitazone; D013755:Tetradecanoylphorbol Acetate
keywords: PPARγ; acute monocytic leukemia; caspase-1; macrophage differentiation; nuclear factor-κB