Vitamin C inhibited FasL-induced apoptotic death of mouse dendritic cells through c-FLIP expression

Vitamin C (VitC) is a potent antioxidant and contributes as an apoptosis inhibitor by preventing death receptor-triggered caspase 8 activity. Fas ligand (FasL) induces the apoptotic cell death via activation of Fas signaling, which is dependent on the expression level of anti-apoptotic molecule c-FLIP (FADD-like IL-1beta-converting enzyme-inhibitory proteins). The present study addressed the effects of VitC on survival of dendritic cells (DCs), a regulator of innate and adaptive immunity. To this end, mouse bone marrow cells were isolated and cultured to attain bone marrow-derived DCs (BMDCs). The cells were treated with FasL in the presence or absence of VitC. Real time RT-PCR, Western blotting and FACS analysis were performed to determine different hallmarks of DC apoptosis. As a result, FasL treatment resulted in activation of caspase 8 and stimulation of cell membrane scrambling, the effects were supressed when VitC was present in the cell culture or the cells were transfected with FLIP siRNA. In conclusion, VitC prevented FasL-triggered DC apoptosis mediated through the expression of c-FLIP.

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J-LEAPS Vaccines Mature Mouse Bone Marrow Cells to Dendritic Cells-1 (DC1) which can Deliver Protective Immunity

Clinical Immunology ◽

10.1016/j.clim.2010.03.098 ◽

2010 ◽

Vol 135 ◽

pp. S32

Author(s):

Patricia Taylor ◽

Gary Koski ◽

Erin Bailey ◽

Daniel Zimmerman ◽

Ken S. Rosenthal

Keyword(s):

Bone Marrow ◽

Dendritic Cells ◽

Protective Immunity ◽

Bone Marrow Cells ◽

Mouse Bone Marrow ◽

Mature Mouse ◽

Mouse Bone Marrow Cells ◽

Marrow Cells

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Differentiation of Dendritic Cells in Cultures of Rat and Mouse Bone Marrow Cells

Advances in Experimental Medicine and Biology - Dendritic Cells in Fundamental and Clinical Immunology ◽

10.1007/978-1-4615-2930-9_42 ◽

1993 ◽

pp. 251-255 ◽

Cited By ~ 2

Author(s):

William E. Bowers ◽

Shengqiang Yu ◽

Syeedur Khandkar

Keyword(s):

Bone Marrow ◽

Dendritic Cells ◽

Bone Marrow Cells ◽

Mouse Bone Marrow ◽

Mouse Bone Marrow Cells ◽

Marrow Cells

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Distinct Roles of the Antiapoptotic Effectors NleB and NleF from Enteropathogenic Escherichia coli

Infection and Immunity ◽

10.1128/iai.01071-16 ◽

2017 ◽

Vol 85 (4) ◽

Cited By ~ 14

Author(s):

Georgina L. Pollock ◽

Clare V. L. Oates ◽

Cristina Giogha ◽

Tania Wong Fok Lung ◽

Sze Ying Ong ◽

...

Keyword(s):

Escherichia Coli ◽

Fas Ligand ◽

Death Receptor ◽

Effector Proteins ◽

Host Cells ◽

Caspase 8 ◽

Death Domain ◽

Content Type ◽

Fas Signaling

ABSTRACT During infection, enteropathogenic Escherichia coli (EPEC) translocates effector proteins directly into the cytosol of infected enterocytes using a type III secretion system (T3SS). Once inside the host cell, these effector proteins subvert various immune signaling pathways, including death receptor-induced apoptosis. One such effector protein is the non-locus of enterocyte effacement (LEE)-encoded effector NleB1, which inhibits extrinsic apoptotic signaling via the FAS death receptor. NleB1 transfers a single N-acetylglucosamine (GlcNAc) residue to Arg117 in the death domain of Fas-associated protein with death domain (FADD) and inhibits FAS ligand (FasL)-stimulated caspase-8 cleavage. Another effector secreted by the T3SS is NleF. Previous studies have shown that NleF binds to and inhibits the activity of caspase-4, -8, and -9 in vitro. Here, we investigated a role for NleF in the inhibition of FAS signaling and apoptosis during EPEC infection. We show that NleF prevents the cleavage of caspase-8, caspase-3, and receptor-interacting serine/threonine protein kinase 1 (RIPK1) in response to FasL stimulation. When translocated into host cells by the T3SS or expressed ectopically, NleF also blocked FasL-induced cell death. Using the EPEC-like mouse pathogen Citrobacter rodentium, we found that NleB but not NleF contributed to colonization of mice in the intestine. Hence, despite their shared ability to block FasL/FAS signaling, NleB and NleF have distinct roles during infection.

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A novel bulk-culture method for generating mature dendritic cells from mouse bone marrow cells

Journal of Immunological Methods ◽

10.1016/s0022-1759(02)00013-3 ◽

2002 ◽

Vol 262 (1-2) ◽

pp. 145-157 ◽

Cited By ~ 90

Author(s):

Young-Ik Son ◽

Shin-ichi Egawa ◽

Tomohide Tatsumi ◽

Richard E. Redlinger ◽

Pawel Kalinski ◽

...

Keyword(s):

Bone Marrow ◽

Dendritic Cells ◽

Bone Marrow Cells ◽

Culture Method ◽

Mouse Bone Marrow ◽

Mouse Bone Marrow Cells ◽

Bulk Culture ◽

Marrow Cells

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Vitamin C treatment of mouse bone marrow-derived dendritic cells enhanced CD8+ memory T cell production capacity of these cells in vivo

Immunobiology ◽

10.1016/j.imbio.2014.03.006 ◽

2014 ◽

Vol 219 (7) ◽

pp. 554-564 ◽

Cited By ~ 14

Author(s):

Young-Joo Jeong ◽

Jin-Hee Kim ◽

Jun-Man Hong ◽

Jae Seung Kang ◽

Hang-Rae Kim ◽

...

Keyword(s):

Bone Marrow ◽

Dendritic Cells ◽

T Cell ◽

Vitamin C ◽

Production Capacity ◽

Mouse Bone Marrow ◽

Cell Production ◽

Memory T Cell

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Faculty Opinions recommendation of Selective and efficient generation of functional Batf3-dependent CD103+ dendritic cells from mouse bone marrow.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718523045.793502277 ◽

2014 ◽

Author(s):

Jakub Tolar ◽

Holger Fey

Keyword(s):

Bone Marrow ◽

Dendritic Cells ◽

Mouse Bone Marrow ◽

Efficient Generation

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Faculty Opinions recommendation of GM-CSF Mouse Bone Marrow Cultures Comprise a Heterogeneous Population of CD11c(+)MHCII(+) Macrophages and Dendritic Cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725566020.793507731 ◽

2015 ◽

Author(s):

Clotilde Théry ◽

Elodie Segura

Keyword(s):

Bone Marrow ◽

Dendritic Cells ◽

Heterogeneous Population ◽

Mouse Bone Marrow ◽

Gm Csf ◽

Bone Marrow Cultures ◽

Marrow Cultures

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Luteolin transforms the polarity of bone marrow-derived macrophages to regulate the cytokine storm

Journal of Inflammation ◽

10.1186/s12950-021-00285-5 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Shuxia Wang ◽

Shuhang Xu ◽

Jing Zhou ◽

Li Zhang ◽

Xiaodong Mao ◽

...

Keyword(s):

Bone Marrow ◽

Inflammatory Responses ◽

Bone Marrow Cells ◽

Membrane Surface ◽

Inflammatory Factors ◽

Mouse Bone Marrow ◽

Macrophage Polarisation ◽

Ifn Γ ◽

Anti Inflammatory ◽

M1 Type

Abstract Background Macrophages are indispensable regulators of inflammatory responses. Macrophage polarisation and their secreted inflammatory factors have an association with the outcome of inflammation. Luteolin, a flavonoid abundant in plants, has anti-inflammatory activity, but whether luteolin can manipulate M1/M2 polarisation of bone marrow-derived macrophages (BMDMs) to suppress inflammation is still unclear. This study aimed to observe the effects of luteolin on the polarity of BMDMs derived from C57BL/6 mice and the expression of inflammatory factors, to explore the mechanism by which luteolin regulates the BMDM polarity. Methods M1-polarised BMDMs were induced by lipopolysaccharide (LPS) + interferon (IFN)-γ and M2-polarisation were stimulated with interleukin (IL)-4. BMDM morphology and phagocytosis were observed by laser confocal microscopy; levels of BMDM differentiation and cluster of differentiation (CD)11c or CD206 on the membrane surface were assessed by flow cytometry (FCM); mRNA and protein levels of M1/M2-type inflammatory factors were performed by qPCR and ELISA, respectively; and the expression of p-STAT1 and p-STAT6 protein pathways was detected by Western-blotting. Results The isolated mouse bone marrow cells were successfully differentiated into BMDMs, LPS + IFN-γ induced BMDM M1-phenotype polarisation, and IL-4 induced M2-phenotype polarisation. After M1-polarised BMDMs were treated with luteolin, the phagocytosis of M1-polarized BMDMs was reduced, and the M1-type pro-inflammatory factors including IL-6, tumour necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), and CD86 were downregulated while the M2-type anti-inflammatory factors including IL-10, IL-13, found in inflammatory zone (FIZZ)1, Arginase (Arg)1 and CD206 were upregulated. Additionally, the expression of M1-type surface marker CD11c decreased. Nevertheless, the M2-type marker CD206 increased; and the levels of inflammatory signalling proteins phosphorylated signal transducer and activator of transcription (p-STAT)1 and p-STAT6 were attenuated and enhanced, respectively. Conclusions Our study suggests that luteolin may transform BMDM polarity through p-STAT1/6 to regulate the expression of inflammatory mediators, thereby inhibiting inflammation. Naturally occurring luteolin holds promise as an anti-inflammatory and immunomodulatory agent.

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