The phenotype and functional alterations of macrophages in mice with hyperglycemia for long term

Sun, Chao; Sun, Lina; Ma, Hui; Peng, Jiao; Yu, Zhen; Duan, Kaizhong; Liu, Guangwei; Ding, Wenjun; Zhao, Yong

doi:10.1002/jcp.22891

Cited by 87 publications

(80 citation statements)

References 45 publications

(50 reference statements)

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“…Bone marrow cells were cultured with DMEM containing 10% (V/V) FBS and 10 ng/ml of mouse granulocyte-macrophage colony-stimulating factor (GM-CSF) for 7-12 days to obtain BMDMs 29 . The non-adherent cells and loosely attached cells were washed by swirling the plates on day 3, 5, 7, and 9 30,31 .…”

Section: Cell Preparationmentioning

confidence: 99%

TSC1 controls IL-1β expression in macrophages via mTORC1-dependent C/EBPβ pathway

et al. 2015

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The tuberous sclerosis complex 1 (TSC1) is a tumor suppressor that inhibits the mammalian target of rapamycin (mTOR), which serves as a key regulator of inflammatory responses after bacterial stimulation in monocytes, macrophages, and primary dendritic cells. Previous studies have shown that TSC1 knockout (KO) macrophages produced increased inflammatory responses including tumor necrosis factor-a (TNF-a) and IL-12 to pro-inflammatory stimuli, but whether and how TSC1 regulates pro-IL-1b expression remains unclear. Here using a mouse model in which myeloid lineage-specific deletion of TSC1 leads to constitutive mTORC1 activation, we found that TSC1 deficiency resulted in impaired expression of pro-IL-1b in macrophages following lipopolysaccharide stimulation. Such decreased pro-IL-1b expression in TSC1 KO macrophages was rescued by reducing mTORC1 activity with rapamycin or deletion of mTOR. Rictor deficiency has no detectable effect on pro-IL-1b synthesis, suggesting that TSC1 positively controls pro-IL-1b expression through mTORC1 pathway. Moreover, mechanism studies suggest that mTORC1-mediated downregulation of the CCAAT enhancer-binding protein (C/EBPb) critically contributes to the defective pro-IL-1b expression. Overall, these findings highlight a critical role of TSC1 in regulating innate immunity by control of the mTOR1-C/EBPb pathway. Cellular & Molecular Immunology

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Section: Cell Preparationmentioning

confidence: 99%

TSC1 controls IL-1β expression in macrophages via mTORC1-dependent C/EBPβ pathway

et al. 2015

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“…Lysates were prepared using the following lysis buffer (pH 8): 50 mM TrisHCl and 1% Triton X-100, with a protease inhibitor mixture (AEBSF, pepstatin A, E-64, bestatin, leupeptin, and aprotinin) from Sigma-Aldrich (28). The concentration of total protein was measured by bicinchoninic acid analysis (Pierce, Rockford, IL).…”

Section: Immunoprecipitationmentioning

confidence: 99%

Phosphatase Wip1 Negatively Regulates Neutrophil Migration and Inflammation

Sun

Liu

et al. 2014

The Journal of Immunology

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Neutrophils are critically involved in host defense and tissue damage. Intrinsic signal mechanisms controlling neutrophil activities are poorly defined. We found that the expression of wild-type p53-induced phosphatase 1 (Wip1) in mouse and human neutrophils was downregulated quickly after neutrophil activation through JNK-microRNA-16 pathway. Importantly, the Wip1 expression level was negatively correlated with inflammatory cytokine productions of neutrophils in sepsis patients. Wip1-deficient mice displayed increased bactericidal activities to Staphylococcus aureus and were hypersensitive to LPS-induced acute lung damage with increased neutrophil infiltration and inflammation. Mechanism studies showed that the enhanced inflammatory activity of neutrophils caused by Wip1 deficiency was mediated by p38 MAPK-STAT1 and NF-κB pathways. The increased migration ability of Wip1KO neutrophils was mediated by the decreased CXCR2 internalization and desensitization, which was directly regulated by p38 MAPK activity. Thus, our findings identify a previously unrecognized function of Wip1 as an intrinsic negative regulator for neutrophil proinflammatory cytokine production and migration through multiple signal pathways.

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“…2/2 peritoneal exudate macrophages (PEMs) were isolated as described previously (29,30). A total of 5 3 10 5 PEMs were stimulated with 50 ng/ml IFN-g (PeproTech) and 1 mg/ml LPS (Escherichia coli III: B4; Sigma-Aldrich) in 24-well plates for 24 h at 37˚C and 5% CO 2 .…”

Section: Wt and Smad3mentioning

confidence: 99%

“…A total of 5 3 10 5 PEMs were stimulated with 50 ng/ml IFN-g (PeproTech) and 1 mg/ml LPS (Escherichia coli III: B4; Sigma-Aldrich) in 24-well plates for 24 h at 37˚C and 5% CO 2 . To detect intracellular TNF-a and IL-6 by FCM, 1 ml/ml brefeldin A (BD GolgiPlug; BD Biosciences) was added during the last 8 h of culture (29). TNF-a, IL-6, and iNOS mRNA was measured by real-time PCR.…”

Section: Wt and Smad3mentioning

confidence: 99%

Smad3-Deficient CD11b+Gr1+ Myeloid-Derived Suppressor Cells Prevent Allograft Rejection via the Nitric Oxide Pathway

Wang

Sun

Chen

et al. 2012

The Journal of Immunology

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Immunosuppressive CD11b+Gr1+ myeloid-derived suppressor cells and TGF-β have been shown to negatively regulate host immunity against allografts. Our results demonstrated that Smad3-deficient mice or mice reconstituted with Smad3-deficient hematopoietic cells rejected allogeneic skin or heart grafts in a significantly slower manner compared with littermates or wild-type (WT) control mice. Transplanted Smad3−/− recipients produced markedly less anti-donor IgG Abs, especially IgG1 and IgG2b subclasses. T cells in alloskin-grafted Smad3-deficient mice were more likely to participate in a Th2-type immune response, as evidenced by more Th2-specific transcription factor, GATA3 expression, and increased IL-4 and IL-10 production, as well as less Th1-specific transcription factor, T-bet expression, and decreased IL-2 and IFN-γ production. More CD11b+Gr1+ neutrophil infiltration and less monocyte/macrophage and T cell infiltration in allografts were observed in Smad3−/− recipients compared with WT recipients. Increased CXCL1 and CXCL2 as well as decreased CCL3, MCP-1, and RANTES chemokines in allografts of Smad3−/− recipients were consistently detected by real-time PCR. Further studies indicated that the increased CD11b+Gr1+ myeloid cells in Smad3-deficient mice were immunosuppressive and responsible for the delayed allograft rejection mainly via an NO-dependent pathway. Thus, this study identifies Smad3 as an intrinsic negative regulator that critically inhibits the differentiation and function of immunosuppressive CD11b+Gr1+ myeloid-derived suppressor cells.

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The phenotype and functional alterations of macrophages in mice with hyperglycemia for long term

Cited by 87 publications

References 45 publications

TSC1 controls IL-1β expression in macrophages via mTORC1-dependent C/EBPβ pathway

TSC1 controls IL-1β expression in macrophages via mTORC1-dependent C/EBPβ pathway

Phosphatase Wip1 Negatively Regulates Neutrophil Migration and Inflammation

Smad3-Deficient CD11b+Gr1+ Myeloid-Derived Suppressor Cells Prevent Allograft Rejection via the Nitric Oxide Pathway

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