scholarly journals Suppression of Dendritic Cell Maturation by Kefir Peptides Alleviates Collagen-Induced Arthritis in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Chien-Fu Chen ◽  
Hsin-Pei Li ◽  
Ya-Hsuan Chao ◽  
Min-Yu Tu ◽  
Chih-Ching Yen ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Inflammatory Cytokine ◽  
Bone Erosion ◽  
Joint Inflammation ◽  
Mapk Signaling ◽  
High Dose ◽  
Mouse Bone Marrow ◽  
Collagen Induced Arthritis ◽  
Dc Maturation

Arthritis is a disorder that is characterized by joint inflammation and other symptoms. Rheumatoid arthritis (RA), an autoimmune disease, is one of the most common arthritis in worldwide. Inflammation of the synovium is the main factor that triggers bone erosion in the joints in RA, but the pathogenesis of RA is not clearly understood. Kefir grain-fermented products have been demonstrated to enhance immune function and exhibit immune-modulating bioactivities. This study aims to explore the role of kefir peptides (KPs) on the regulation of dendritic cell, which are found in RA synovial fluid, and the protection effects of KPs on mice with collagen-induced arthritis (CIA). Immature mouse bone marrow-derived dendritic cells (BMDCs) were treated with KPs (2.2 and 4.4 mg/ml) and then exposed to lipopolysaccharide (LPS) to study the immune regulation function of KPs in dendritic cells. Mice with CIA (n = 5 per group) were orally administrated KPs (3.75 and 7.5 mg/day/kg) for 21 days and therapeutic effect of KPs on mice with arthritis were assessed. In this study, we found that KPs could inhibit surface molecule expression, reduce inflammatory cytokine release, and repress NF-κB and MAPK signaling in LPS-stimulated mouse BMDCs. In addition, a high dose of KPs (7.5 mg/kg) significantly alleviated arthritis symptoms, decreased inflammatory cytokine expression, suppressed splenic DC maturation and decrease the percentage of Th1 and Th17 in the spleens on mice with CIA. Our findings demonstrated that KPs ameliorate CIA in mice through the mechanism of suppressing DC maturation and inflammatory cytokine releases.

Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of collagen-induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion

2004 ◽  
Vol 50 (2) ◽  
pp. 650-659 ◽  
Author(s):  
Erik Lubberts ◽  
Marije I. Koenders ◽  
Birgitte Oppers-Walgreen ◽  
Liduine van den Bersselaar ◽  
Christina J. J. Coenen-de Roo ◽  
...  
Keyword(s):  
Bone Erosion ◽  
Joint Inflammation ◽  
Cartilage Destruction ◽  
Interleukin 17 ◽  
Collagen Induced Arthritis

scholarly journals NFκB- and MAP-Kinase Signaling Contribute to the Activation of Murine Myeloid Dendritic Cells by a Flagellin A:Allergen Fusion Protein

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 355 ◽  
Author(s):  
Moeller ◽  
Wolfheimer ◽  
Goretzki ◽  
Scheurer ◽  
Schülke
Keyword(s):  
Dendritic Cells ◽  
Fusion Protein ◽  
Map Kinase ◽  
Inflammatory Cytokine ◽  
Allergic Sensitization ◽  
Birch Pollen ◽  
Mapk Signaling ◽  
Cytokine Secretion ◽  
Myeloid Dendritic Cells ◽  
Anti Inflammatory

Fusion proteins incorporating the TLR5-ligand flagellin are currently undergoing clinical trials as vaccine candidates for many diseases. We recently reported a flagellin:allergen fusion protein containing the TLR5-ligand flagellin A (FlaA) from Listeria monocytogenes and the major birch pollen allergen Bet v 1 (rFlaA:Betv1) to prevent allergic sensitization in an experimental mouse model. This study analyzes the signaling pathways contributing to rFlaA:Betv1-mediated pro- and anti-inflammatory cytokine secretion and cell metabolism in myeloid dendritic cells (mDCs) in vitro. The influence of mammalian target of rapamycin (mTOR)-, NF?B-, and MAP kinase (MAPK)-signaling on cytokine secretion and metabolic activity of bone marrow (BM)-derived mDCs stimulated with rFlaA:Betv1 were investigated by pre-treatment with either mTOR- (rapamycin), NF?B- (dexamethason, BMS-345541, TPCA-1, triptolide, or BAY-11) or MAPK- (SP600125, U0126, or SB202190) inhibitors, respectively. rFlaA:Betv1-mediated IL-10 secretion as well as activation of mDC metabolism, rather than pro-inflammatory cytokine secretion, were inhibited by rapamycin. Inhibition of NFκB-signaling suppressed rFlaA:Betv1-induced IL-12, while inhibition of MAPK-signaling dose-dependently suppressed rFlaA:Betv1-induced IL-10 as well as pro-inflammatory IL-6 and TNF-α production. Notably, with the exception of a partial JNK-dependency, rFlaA:Betv1-mediated effects on mDC metabolism were mostly NF?B- and MAPK-independent. Therefore, MAPK-mediated activation of both NFκB- and mTOR-signaling likely is a key pathway for the production of pro- and anti-inflammatory cytokines by flagellin fusion protein vaccines.

scholarly journals High-dose UV-B radiation alters human dendritic cell costimulatory activity but does not allow dendritic cells to tolerize T lymphocytes to alloantigen in vitro

Blood ◽  
1993 ◽  
Vol 81 (11) ◽  
pp. 2987-2997 ◽  
Author(s):  
JW Young ◽  
J Baggers ◽  
SA Soergel
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
T Lymphocytes ◽  
Interleukin 2 ◽  
Secondary Response ◽  
High Dose ◽  
Cell Responses ◽  
Cell Expression

Abstract Human blood dendritic cells require UV-B radiation (290 to 320 nm) in excess of 1,000 J/m2 to inhibit their stimulation of primary T-cell responses to alloantigen by 60% to 70% or more. The effect is twofold to threefold greater in the allogeneic mixed leukocyte reaction (MLR) than in polyclonal mitogenesis using comparable numbers of dendritic cells and doses of UV-B radiation. UV-B radiation does not significantly alter dendritic cell viability at the doses administered. Dendritic cell expression of important costimulatory ligands, eg, B7/BB1 and ICAM-1/CD54, is reduced in proportion to the dose of UV-B light administered. UV-B irradiated dendritic cells nevertheless initiate stable contacts with primary alloreactive T lymphocytes that are sufficient to prime T-cell responsiveness to interleukin-2 (IL-2). Subsequent proliferation is severely abrogated without supplemental lymphokine, while T-cell alloreactivity is preserved in a secondary response, irrespective of primary exposure to UV-B irradiated dendritic cells.

Randomized Trial of GM-CSF and G-CSF Following High-Dose Cytarabine and Mitoxantrone Chemotherapy for Relapsed and Refractory Acute Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4574-4574
Author(s):  
Maria R. Baer ◽  
Laurie A. Ford ◽  
Brian N. Bundy ◽  
Sheila M. Tighe ◽  
Kieran L. O’Loughlin ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
High Dose ◽  
Myeloid Dendritic Cell ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
High Dose Cytarabine ◽  
Stimulating Factor ◽  
Subsequent Relapse ◽  
Count Recovery

Abstract Patients with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) refractory to or in relapse following induction chemotherapy have a poor prognosis, and inducing an immune response to autologous AML or ALL cells following chemotherapy is an attractive approach to improving outcome. Immune responses to autologous leukemia cells may be stimulated by dendritic cell presentation of leukemia cell antigens, dendritic cells may be deficient in acute leukemia, and administration of the recombinant hematopoietic growth factors granulocyte-monocyte colony-stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF) following chemotherapy may increase dendritic cell numbers. We compared the effects of GM-CSF and G-CSF administered following high-dose chemotherapy. Adult relapsed and refractory AML and ALL patients received salvage chemotherapy consisting of high-dose cytarabine 3 g/m2 (1.5 g/m2 for age ≥50 years) over one hour every 12 hours × 12 doses and mitoxantrone 12 mg/m2 daily × 3 (HiDAC/Mx), and at completion of chemotherapy were randomized to receive GM-CSF 250 mcg/m2 or G-CSF 5 mcg/kg daily beginning 12 hours after the last chemotherapy dose, until absolute neutrophil count ≥5 × 109〈1 year) and late (≥1 year) first and subsequent relapse. Peripheral blood was collected when ANC reached 5 × 109/L for measurement of myeloid dendritic cell (lineage-negative, HLADr+, CD11c+) percentages by flow cytometry. Sixty patients were enrolled, ages 18 to 82 (median 66) years, 41 male and 19 female, 47 with AML and 13 with ALL, and 15 with primary refractory disease, 27 in early and 17 in late first relapse and one in subsequent relapse; 6 had relapsed following allogeneic transplantation. Overall, 22 of 60 patients (37%) achieved CR and 4 (7%) CR with incomplete count recovery (CRi), while 23 (38%) had resistant disease and 11 (18%) died. The regimen was generally well tolerated, the most frequent grade ≥4 toxicities pulmonary, infectious and cardiac, in 8, 7 and 6 patients, respectively, and 13 patients subsequently received transplant-based therapies (9 allogeneic, 4 autologous). 56 patients were randomized, as 4 died or stopped therapy before randomization, and randomization was to GM-CSF in 29 patients and G-CSF in 27. CR and CRi were achieved by 13 and 1 patients of 29 patients receiving GM-CSF and 9 and 3 of 27 receiving G-CSF (p NS, Fisher’s Exact Text). ANC ≥0.5 was achieved at 22 to 98 days (median 27) from start of chemotherapy in 25 GM-CSF patients and at 18 to 65 days (median 25) in 20 G-CSF patients (p=0.08, Wilcoxon Rank Sum Test). Toxicities did not differ significantly on the two arms. Only 17 patients (G-CSF: 7 and GM-CSF: 10) had blood samples submitted and successfully studied for myeloid dendritic cell percentages. Myeloid dendritic cell percentages were 0 to 40 (median 22), and the comparison by treatment group showed no evidence of a difference. In summary, HiDAC/Mx is an effective salvage regimen in this high-risk population and may serve as a bridge to transplant-based therapies or, possibly, a backbone for targeted therapies, myeloid dendritic cells are present at count recovery in patients receiving GM-CSF or G-CSF following HiDAC/Mx, and treatment outcome, toxicities, count recovery and myeloid dendritic cell percentages did not differ in patients receiving GM-CSF or G-CSF following HiDAC/Mx.

scholarly journals Bacterial Probiotic Modulation of Dendritic Cells

2004 ◽  
Vol 72 (6) ◽  
pp. 3299-3309 ◽  
Author(s):  
Maureen Drakes ◽  
Thomas Blanchard ◽  
Steven Czinn
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
Cell Surface ◽  
Fluorescent Antibody ◽  
Bacterial Flora ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Dose ◽  
Surface Phenotype

ABSTRACT Intestinal dendritic cells are continually exposed to ingested microorganisms and high concentrations of endogenous bacterial flora. These cells can be activated by infectious agents and other stimuli to induce T-cell responses and to produce chemokines which recruit other cells to the local environment. Bacterial probiotics are of increasing use against intestinal disorders such as inflammatory bowel disease. They act as nonpathogenic stimuli within the gut to regain immunologic quiescence. This study was designed to determine the ability of a bacterial probiotic cocktail VSL#3 to alter cell surface antigen expression and cytokine production in bone marrow-derived dendritic cell-enriched populations. Cell surface phenotype was monitored by monoclonal fluorescent antibody staining, and cytokine levels were quantitated by enzyme-linked immunosorbent assay. High-dose probiotic upregulated the expression of C80, CD86, CD40, and major histocompatibility complex class II I-Ad. Neither B7-DC or B7RP-1 was augmented after low-dose probiotic or Lactobacillus casei treatment, but B7RP-1 showed increased expression on dendritic cells stimulated with the gram-negative bacterium Escherichia coli. Functional studies showed that probiotic did not enhance the ability of dendritic cells to induce allogeneic T-cell proliferation, as was observed for E. coli. Substantial enhancement of interleukin-10 release was observed in dendritic cell-enriched culture supernatants after 3 days of probiotic stimulation. These results demonstrate that probiotics possess the ability to modulate dendritic cell surface phenotype and cytokine release in granulocyte-macrophage colony-stimulating factor-stimulated bone marrow-derived dendritic cells. Regulation of dendritic cell cytokines by probiotics may contribute to the benefit of these molecules in treatment of intestinal diseases.

scholarly journals Expression of vFLIP in a Lentiviral Vaccine Vector Activates NF-κB, Matures Dendritic Cells, and Increases CD8+ T-Cell Responses

2008 ◽  
Vol 83 (4) ◽  
pp. 1555-1562 ◽  
Author(s):  
Helen M. Rowe ◽  
Luciene Lopes ◽  
Najmeeyah Brown ◽  
Sofia Efklidou ◽  
Timothy Smallie ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Tumor Therapy ◽  
T Cell Response ◽  
Vaccine Vector ◽  
Interleukin 12 ◽  
Mouse Bone Marrow ◽  
Dc Maturation

ABSTRACT Lentiviral vectors deliver antigens to dendritic cells (DCs) in vivo, but they do not trigger DC maturation. We therefore expressed a viral protein that constitutively activates NF-κB, vFLIP from Kaposi's sarcoma-associated herpesvirus (KSHV), in a lentivector to mature DCs. vFLIP activated NF-κB in mouse bone marrow-derived DCs in vitro and matured these DCs to a similar extent as lipopolysaccharide; costimulatory markers CD80, CD86, CD40, and ICAM-1 were upregulated and tumor necrosis factor alpha and interleukin-12 secreted. The vFLIP-expressing lentivector also matured DCs in vivo. When we coexpressed vFLIP in a lentivector with ovalbumin (Ova), we found an increased immune response to Ova; up to 10 times more Ova-specific CD8+ T cells secreting gamma interferon were detected in the spleens of vFLIP_Ova-immunized mice than in the spleens of mice immunized with GFP_Ova. Furthermore, this increased CD8+ T-cell response correlated with improved tumor-free survival in a tumor therapy model. A single immunization with vFLIP_Ova also reduced the parasite load when mice were challenged with OVA-Leishmania donovani. In conclusion, vFLIP from KSHV is a DC activator, maturing DCs in vitro and in vivo. This demonstrates that NF-κB activation is sufficient to induce many aspects of DC maturation and that expression of a constitutive NF-κB activator can improve the efficacy of a vaccine vector.

scholarly journals TARM1 contributes to development of arthritis by activating dendritic cells through recognition of collagens

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rikio Yabe ◽  
Soo-Hyun Chung ◽  
Masanori A. Murayama ◽  
Sachiko Kubo ◽  
Kenji Shimizu ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Bone Marrow Cells ◽  
Dendritic Cell Maturation ◽  
Mouse Bone Marrow ◽  
Gm Csf ◽  
Good Target ◽  
Antigen Presenting ◽  
Dc Maturation

AbstractTARM1 is a member of the leukocyte immunoglobulin-like receptor family and stimulates macrophages and neutrophils in vitro by associating with FcRγ. However, the function of this molecule in the regulation of the immune system is unclear. Here, we show that Tarm1 expression is elevated in the joints of rheumatoid arthritis mouse models, and the development of collagen-induced arthritis (CIA) is suppressed in Tarm1–/– mice. T cell priming against type 2 collagen is suppressed in Tarm1–/– mice and antigen-presenting ability of GM-CSF-induced dendritic cells (GM-DCs) from Tarm1–/– mouse bone marrow cells is impaired. We show that type 2 collagen is a functional ligand for TARM1 on GM-DCs and promotes DC maturation. Furthermore, soluble TARM1-Fc and TARM1-Flag inhibit DC maturation and administration of TARM1-Fc blocks the progression of CIA in mice. These results indicate that TARM1 is an important stimulating factor of dendritic cell maturation and could be a good target for the treatment of autoimmune diseases.

scholarly journals Measles virus modulates chemokine release and chemotactic responses of dendritic cells

2009 ◽  
Vol 90 (4) ◽  
pp. 909-914 ◽  
Author(s):  
Marion Abt ◽  
Evelyn Gassert ◽  
Sibylle Schneider-Schaulies
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
Chemokine Receptor ◽  
Measles Virus ◽  
Receptor Expression ◽  
Cell Recruitment ◽  
Receptor Modulation ◽  
And Function ◽  
Dc Maturation

Interference with dendritic cell (DC) maturation and function is considered to be central to measles virus (MV)-induced immunosuppression. Temporally ordered production of chemokines and switches in chemokine receptor expression are essential for pathogen-driven DC maturation as they are prerequisites for chemotaxis and T cell recruitment. We found that MV infection of immature monocyte-derived DCs induced transcripts specific for CCL-1, -2, -3, -5, -17 and -22, CXCL-10 and CXCL-11, yet did not induce CXCL-8 (interleukin-8) and CCL-20 at the mRNA and protein level. Within 24 h post-infection, T cell attraction was not detectably impaired by these cells. MV infection failed to promote the switch from CCR5 to CCR7 expression and this correlated with chemotactic responses of MV-matured DC cultures to CCL-3 rather than to CCL-19. Moreover, the chemotaxis of MV-infected DCs to either chemokine was compromised, indicating that MV also interferes with this property independently of chemokine receptor modulation.

scholarly journals Anti-inflammatory Activity of Formononetin in a Collagen-induced Arthritis Mouse Model ofRheumatoid Arthritis

2020 ◽  
Author(s):  
Ying Zhao ◽  
GUIWU QU ◽  
Wenxue Lu ◽  
Qing Lv ◽  
Wenxing Shi ◽  
...  
Keyword(s):  
Mouse Model ◽  
Bone Erosion ◽  
Bone Destruction ◽  
Treated Group ◽  
Control Group ◽  
High Dose ◽  
Collagen Induced Arthritis ◽  
Hind Limbs ◽  
Healthy Control ◽  
Anti Inflammatory

Abstract Background: Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic inflammation of the joints, leading to bone erosion and joint dysfunction. Although there are options for the treatment of RA, safer and more effective drugs are still being sought. Formononetin (FMN) is an isoflavonoid compound found in various plants, such as Astragalus propinquus Schischkin and Spatholobus suberectus. It has anti-tumor, anti-bacterial, anti-lipid peroxidation, and estrogen-like activities，and is a noteworthy compound for screening of anti-RA drugs. Methods: To investigate the anti-inflammatory effects of FMN in a collagen-induced arthritis (CIA) mouse model, thirty-six C57BL/6 mice were randomly divided into 6 groups: a healthy control group and 5 CIA groups. Arthritis was induced the CIA groups using chicken collagen type II. The CIA groups were divided in a control group (RA), a tripterygium glycosides (10 mg/kg body weight) treated group (TG), a low-dose (50 mg/kg) FMN group (FMN-L), a middle-dose(100mg/kg) FMN group (FMN-M), and a high-dose (200 mg/kg) FMN group (FMN-H). The control mice and CIA mice in the RA group were treated with an equal volume of 5% carboxymethylcellulose sodium. Drugs were delivered three times a week for four weeks, and the bodyweight, food-uptake, and swelling of the paws were monitored during the treatment process. Inflammatory cytokines and other biochemical indexes in the serum and joint tissues were analyzed, along with the expression levels of NF-κB pathway-related proteins (IκBα, p65, p-p65, TIPE2, and PCNP) in the spleen. Histopathological examinations were processed for the hind limbs. Results: FMN-M dramatically reduced the arthritis index in the CIA mice, inhibited the inflammatory cell infiltration, and prevented damage to the synovium and cartilage. Mechanistic studies suggested that FMN might reduce inflammation by inhibiting IκB-α degradation and by regulating the expression and release of NF-κB p65. Conclusions: These data suggest that FMN might be an active therapeutic agent for RA by preventing bone destruction, regulating inflammatory mediators, and suppressing NF-κB signaling pathways.

scholarly journals The X-Linked Inhibitor of Apoptosis Protein Inhibitor Embelin Suppresses Inflammation and Bone Erosion in Collagen Antibody Induced Arthritis Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Anak A. S. S. K. Dharmapatni ◽  
Melissa D. Cantley ◽  
Victor Marino ◽  
Egon Perilli ◽  
Tania N. Crotti ◽  
...  
Keyword(s):  
Low Dose ◽  
Bone Erosion ◽  
Joint Inflammation ◽  
Inhibitor Of Apoptosis ◽  
High Dose ◽  
Tartrate Resistant Acid Phosphatase ◽  
Collagen Crosslinks ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein ◽  
Carboxy Terminal

Objective. To investigate the effect of Embelin, an inhibitor of X-Linked Inhibitor of Apoptosis Protein (XIAP), on inflammation and bone erosion in a collagen antibody induced arthritis (CAIA) in mice.Methods. Four groups of mice (n=6per group) were allocated: CAIA untreated mice, CAIA treated with Prednisolone (10 mg/kg/day), CAIA treated with low dose Embelin (30 mg/kg/day), and CAIA treated with high dose Embelin (50 mg/kg/day). Joint inflammation was evaluated using clinical paw score and histological assessments. Bone erosion was assessed using micro-CT, tartrate resistant acid phosphatase (TRAP) staining, and serum carboxy-terminal collagen crosslinks (CTX-1) ELISA. Immunohistochemistry was used to detect XIAP protein. TUNEL was performed to identify apoptotic cells.Results. Low dose, but not high dose Embelin, suppressed inflammation as reflected by lower paw scores (P<0.05) and lower histological scores for inflammation. Low dose Embelin reduced serum CTX-1 (P<0.05) and demonstrated lower histological score and TRAP counting, and slightly higher bone volume as compared to CAIA untreated mice. XIAP expression was not reduced but TUNEL positive cells were more abundant in Embelin treated CAIA mice.Conclusion. Low dose Embelin suppressed inflammation and serum CTX-1 in CAIA mice, indicating a potential use for Embelin to treat pathological bone loss.

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