scholarly journals The Protective Effects of the Ethyl Acetate Part of Er MiaoSan on Adjuvant Arthritis Rats by Regulating the Function of Bone Marrow-Derived Dendritic Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Jiemin Ding ◽  
Min Liu ◽  
Zihua Xuan ◽  
Meng li Liu ◽  
Ning Wang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Proliferation ◽  
Dendritic Cells ◽  
Ethyl Acetate ◽  
B Cell ◽  
Adjuvant Arthritis ◽  
Ethyl Acetate Fraction ◽  
Costimulatory Molecules ◽  
Inflammatory Factor ◽  
Protective Effects

Aims. The aim of this study was to evaluate the protective effects of Er Miao San (EMS) and the regulative function of bone marrow-derived dendritic cells (BMDCs) on adjuvant arthritis (AA) in rats. Methods. The ethyl acetate part of EMS (3 g/kg, 1.5 g/kg, and 0.75 g/kg) was orally administered from day 15 after immunization to day 29. The polyarthritis index and paw swelling were measured, the ankle joint pathological changes were observed using hematoxylin-eosin (HE) staining, and the spleen and thymus index were determined. Moreover, T and B cell proliferation were determined using the CCK-8 assay. The expression of BMDC surface costimulatory molecules and inflammatory factors were determined using flow cytometry and ELISA kits, respectively. Results. Compared with the AA model rats, the ethyl acetate fraction of EMS obviously reduced paw swelling (from 1.0 to 0.7) and the polyarthritis index (from 12 to 9) P < 0.01 and improved the severity of histopathology P < 0.01 . The treatment using ethyl acetate fraction of EMS significantly reduced the spleen and thymus index P < 0.01 and inhibited T and B cell proliferation P < 0.01 . Moreover, EMS significantly modulated the expression of surface costimulatory molecules in BMDCs, including CD40, CD80, CD86, and major histocompatibility complex class II (MHC-II) P < 0.01 . The results also showed that the ethyl acetate part of EMS significant inhibited the levels of proinflammatory cytokines interleukin- (IL-) 23 tumor necrosis factor- (TNF-) α and inflammatory factor prostaglandin (PG) E2 in the supernatant of BMDCs. However, the level of anti-inflammatory cytokine IL-10 was significantly increased P < 0.01 . Conclusion. These results suggest that the ethyl acetate part of EMS has better protective effects on AA rats, probably by regulating the function of BMDCs and modulating the balance of cytokines.

scholarly journals Effect of the Extract and Constituents From Hancornia speciosa Fruits in Osteoclasts

2019 ◽  
Vol 6 (01) ◽  
pp. e7-e14 ◽  
Author(s):  
Micena Alves e Silva ◽  
Cinthia Pacheco ◽  
Mila Madeira ◽  
Adriana Saraiva ◽  
Elisângela de Freitas ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Ethyl Acetate ◽  
Bone Marrow Cell ◽  
Cell Cultures ◽  
Marrow Cell ◽  
Ethanolic Extract ◽  
Quinic Acid ◽  
Ethyl Acetate Fraction ◽  
Raw 264.7 ◽  
Hancornia Speciosa

Abstract Hancornia speciosa is a medicinal species traditionally used in Brazilian folk medicine to treat a variety of conditions. Compounds isolated from the leaves, bark, and trunk of this plant have shown therapeutic properties, but only recently have the fruits of H. speciosa been explored for potential pharmacological applications. The present study investigated the effects of an ethanolic extract from the fruits, fractions, and compounds thereof in bone resorbing cells. Primary osteoclast cultures from bone marrow cells and osteoclasts derived from a monocyte/macrophage cell line, RAW 264.7, were incubated with different concentrations of the ethanolic extract, ethyl acetate fraction, water fraction, quinic acid, and L-(+)-bornesitol. In RAW 264.7 cell cultures, quinic acid significantly reduced osteoclast formation. In bone marrow cell-derived osteoclasts, the ethyl acetate fraction induced a decrease in the number of osteoclasts, promoting a remarkable reduction in the mean area of those cells and in their resorption activity. The compounds quinic acid and bornesitol also affected bone marrow cell-derived osteoclasts. In both cell cultures, the substances tested did not affect cell viability/proliferation. In conclusion, components extracted from H. speciosa fruit affected the cells responsible for bone resorption, making them promising tools for interference in osteoclastogenesis.

scholarly journals Role of the p38 MAPK/C/EBPβ Pathway in the Regulation of Phenotype and IL-10 and IL-12 Production by Tolerogenic Bone Marrow-Derived Dendritic Cells

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 256 ◽  
Author(s):  
Chantal Guindi ◽  
Alexandre Cloutier ◽  
Simon Gaudreau ◽  
Echarki Zerif ◽  
Patrick P. McDonald ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Dna Binding ◽  
P38 Mapk ◽  
Costimulatory Molecules ◽  
Binding Activity ◽  
Gm Csf ◽  
Dna Binding Activity ◽  
Factor C

Dendritic cells (DCs) play a major role in innate and adaptive immunity and self-immune tolerance. Immunogenic versus tolerogenic DC functions are dictated by their levels of costimulatory molecules and their cytokine expression profile. The transcription factor C/EBPβ regulates the expression of several inflammatory genes in many cell types including macrophages. However, little is known regarding the role of C/EBPβ in tolerogenic versus immunogenic DCs functions. We have previously reported that bone marrow-derived DCs generated with GM-CSF (GM/DCs) acquire the signature of semi-mature tolerogenic IL-10-producing DCs as opposed to immunogenic DCs generated with GM-CSF and IL-4 (IL-4/DCs). Here, we show that tolerogenic GM/DCs exhibit higher levels of phosphorylation and enhanced DNA binding activity of C/EBPβ and CREB than immunogenic IL-4/DCs. We also show that the p38 MAPK/CREB axis and GSK3 play an important role in regulating C/EBPβ phosphorylation and DNA binding activity. Inhibition of p38 MAPK in GM/DCs resulted in a drastic decrease of C/EBPβ and CREB DNA binding activities, a reduction of their IL-10 production and an increase of their IL-12p70 production, a characteristic of immunogenic IL-4/DCs. We also present evidence that GSK3 inhibition in GM/DCs reduced C/EBPβ DNA binding activity and increased expression of costimulatory molecules in GM/DCs and their production of IL-10. Analysis of GM/DCs of C/EBPβ−/− mice showed that C/EBPβ was essential to maintain the semimature phenotype and the production of IL-10 as well as low CD4+ T cell proliferation. Our results highlight the importance of the p38MAPK-C/EBPβ pathway in regulating phenotype and function of tolerogenic GM/DCs.

Protective effects of ethyl acetate fraction ofLawsonia inermisfruits extract against carbon tetrachloride-induced oxidative damage in rat liver

2013 ◽  
Vol 32 (4) ◽  
pp. 694-706 ◽  
Author(s):  
Anis Ben Hsouna ◽  
Saoudi Mongi ◽  
Gérald Culioli ◽  
Yves Blache ◽  
Zohra Ghlissi ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Oxidative Damage ◽  
Ethyl Acetate ◽  
Rat Liver ◽  
Ethyl Acetate Fraction ◽  
Protective Effects

BRAFV600E Mutations Occur In The Hematopoietic Stem Cell Compartment In Hairy Cell Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 816-816
Author(s):  
Stephen S. Chung ◽  
Jae H. Park ◽  
Eunhee Kim ◽  
Young Rock Chung ◽  
Wenhuo Hu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Proliferation ◽  
B Cells ◽  
B Cell ◽  
Bone Marrow Cells ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Hematopoietic Stem ◽  
Mutant Braf

Abstract Hairy cell leukemia (HCL) is a chronic lymphoproliferative disorder recently found to be characterized by somatic BRAFV600E mutations. The malignant cell in HCL exhibits features consistent with a mature B-lymphocyte, including cell-surface expression of the pan-B-cell marker CD19 and monotypic surface immunoglobulins with clonal rearrangements of immunoglobulin heavy and light chains. Despite possessing these stereotypic features, the cell of origin of HCL has been long debated, and no cell type along the continuum of developing B-lymphocytes has been definitively identified as the normal counterpart of HCL cells. We hypothesized that HCL may originate from immature hematopoietic cells, and therefore investigated the hematopoietic-stem/progenitor cell (HSPC) compartment in HCL patients. We found that HCL patients exhibited a significantly increased frequency of immunophenotypically defined long-term hematopoietic stem cells (LT-HSCs; lineage-negative (Lin-neg) CD34+CD38-CD90+CD45RA- cells), pro-B cells (Lin-neg CD10+ cells), and CD34-CD38+ CD10+CD19+ hematogones, as well as a decreased frequency of granulocyte-macrophage progenitor cells (Lin-neg CD34+CD38+CD45RA+CD123+) relative to age-matched normal controls. Sequencing of cDNA from highly pure FACS-sorted cell populations from the bone marrow of HCL patients revealed the presence of the BRAFV600E allele in LT-HSCs and in pro-B cells (Figure). Transplantation of LT-HSCs from the pretreatment bone marrow of HCL patients into NOD/SCID/IL2r-gnull mice resulted in stable human grafts characterized by an expanded B-progenitor population and development of a clonal population of hCD19+hCD103+hCD25+ B cells characteristic of HCL 6 months after transplantation. Together, these data suggest that HCL arises from HSCs that then differentiate into committed B-cells which ultimately give rise to the characteristic clonal B-cell proliferation of HCL. Given the human HSC genetic and functional cell data, we conditionally expressed BRafV600E from its endogenous locus at different stages of hematopoiesis, including in HSPCs and committed B cells. Mice with conditional expression of BRafV600E in Mx1Cre+ BRafV600E knock-in mice died of a lethal hematopoietic malignancy characterized by features of human HCL including splenomegaly, anemia, thrombocytopenia, increased circulating sCD25, and increased clonogenic capacity of B-lineage cells (evidenced by infinite serial replating in the presence of IL-7) (Figure). This disorder was transplantable into lethally-irradiated recipient mice. In contrast, mice with expression of BRafV600E restricted to the B-cell lineage with Cd19 Cre manifested no overt malignant phenotype up to one year of age. Stimulation of these mice with alloantigen through injections of sheep red blood cells resulted in germinal center B-cell hyperplasia, but still did not result in development of a clonal B-cell proliferation. Recent case reports have noted that refractory HCL patients respond to mutant BRAF inhibition with vemurafenib. We investigated the effect of vemurafenib on HSPCs and hematopoiesis in patients treated on a phase II study of the mutant BRAF inhibitor vemurafenib for relapsed/refractory HCL as well as in our in vivo murine models. Flow cytometric analysis of bone marrow cells from vemurafenib treated HCL patients revealed normalization of HSPC frequencies within three months of starting therapy, concomitant with an improvement in peripheral blood counts. Consistent with this, evaluation of the in vitro clonogenic capacity of sorted LT-HSC's from the bone marrow of HCL patients revealed a significant increase in myeloid/erythroid colony formation in HCL patients treated for 3 months with vemurafenib compared to their pretreatment marrows. Likewise, treatment of wildtype mice transplanted with Mx1Cre+ BRafV600E mutant bone marrow cells revealed improvement in anemia and hepatosplenomegaly with in vivo therapy. Overall, these findings link the pathogenesis of HCL to a specific somatic genetic abnormality present in HSCs and provide evidence that mature B-cell malignancies can initiate in the HSC compartment. Moreover, these data suggest that the use of therapies targeting MAP kinase signaling in HCL may lead to durable remissions not only by eliminating the mature leukemic cells but also through targeted inhibition of signaling and survival in HCL initiating cells. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Directing Traffic in Lymph Nodes

2007 ◽  
Vol 15 (5) ◽  
pp. 3-5
Author(s):  
Stephen W. Carmichael ◽  
Ellen D. Remstein
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Dendritic Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Stromal Cells ◽  
Follicular Dendritic Cells ◽  
Adjacent Region ◽  
Reticular Cells ◽  
The Right

How do the right cells get to the right place in lymph nodes? It is known that lymphocytes known as B cells (that originate in the bone marrow) migrate to follicles within the nodes, whereas T cells (that originate in the bone marrow and migrate to the thymus gland) reside in an adjacent region known as the paracortex. By combining confocal, electron, and intravital microscopy, Marc Bajénoff, Jackson Egen, Lily Koo, Jean Pierre Laugier, Frédéric Brau, Nicolas Glaichenhaus, and Ronald Germain have demonstrated a role for the stroma of the node in directing these cells to the appropriate location. The stromal cells that are critical in the B cell follicles are follicular dendritic cells (FDCs) and in the paracortex it's the fibroblastic reticular cells (FRCs).

scholarly journals Interleukin-32 Induce Production of IL-6 in Multiple Myeloma Bone Marrow Stromal Cells

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3253-3253
Author(s):  
Xuanru Lin ◽  
Xing Guo ◽  
Jing Chen ◽  
Qingxiao Chen ◽  
Enfan Zhang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Marrow Stromal Cells ◽  
Inflammatory Factor ◽  
Healthy Controls ◽  
Qrt Pcr ◽  
Stat Pathway

Abstract Background: Multiple myeloma (MM) is closely associated with inflammation. Patients with auto-immune disease、history of infection and other inflammatory disease have higher incidence of MM. IL-6 is the most important inflammatory factor in MM which plays a key role in the proliferation and progression. We previously demonstrated that MM cells were modified by bone marrow stromal cells (BMSCs) that formulate a inflammatory microenvironment in bone marrow (BM) and secret IL-6. How the inflammation makes BMSCs secret IL-6, however, remained undocumented. Our subsequent study compared the differential secretion of peripheral blood (PB) between MM patients and normal people by cytokine array, and showed that interleukin 32(IL-32) is highly expressed in MM patients. IL-32, also named natural killer 4(NK-4), is a newly found inflammatory factor. It was reported in solid tumors IL-32 is a pro-inflammatory factor which triggers a massive amplification of inflammatory process resulting in the change of other inflammatory factor including IL-6,IL-10,TNF-α. In this study, we examined BMSCs cytokines in MM BM and found that IL-32 was a functional factor in the process of inflammation in MM BM microenvironment. Results: First, to test our previous study, we detected IL-32 in BM supernatant and PB supernatant in both MM patients (n=45) and healthy controls (n=13) by ELISA. Result showed that in both BM and PB, MM patients have higher expression of IL-32 compared to healthy controls (P<0.05). Next, total BM cells(both CD138+ and CD138- cells) from MM patients were assayed by qRT-PCR for gene expression analysis.IL-32 were highly expressed in MM BM cells and the CD138+ cells (P<0.05). We also detected IL-32 in MM cell lines (RPMI 8226,OPM-2) and BMSCs isolated from MM patients by qRT-PCR, Western blot, and ELISA, and found that IL-32 was highly expressed in MM cell lines than BMSCs. In contrast, proteinase 3(PR3, receptor of IL-32) was highly expressed in BMSCs compared to MM cell lines. Second, we stimulated the MM BMSCs with recombinant IL-32α, and found that the secretion of IL-6,CCL3 (MIP1-α), CCL4(MIP-1β) were significantly increased and CCL-5(RANTES)and IL-10 were decreased (P<0.05). Further, Western blot was applied to detect the inflammation molecular pathway in BMSCs. JAK-STAT pathway and NF-κB pathway were activated, and the phosphorylation of STAT3 was increased. After we knock down the PR3 in BMSCs, these changes were reduced. We repeated these experiments in BMSCs isolated from 15 different MM patients, the phenomenon mentioned above showed in 11 patients. The recombinant IL-32α was also used to stimulate 8226 and OPM-2 cells, but these two kinds of MM cells didn't secret IL-6, and no significant change in cell proliferation or cell apoptosis. Finally, our group co-cultured the MM BMSCs with 8226 and OPM-2 cells. The secretion of IL-6 and the phosphorylation of JAK-STAT pathway in BMSCs were also increased. Knockdown of IL-32 in 8226 and OPM-2 cells weakened these changes.MM Cell proliferation and cell cycles after co-culture with MM BMSCs are under investigation. Conclusion: our findings suggest that IL-32 is mainly secreted by MM cells. It may not directly promote the MM cells to grow. However, IL-32 promote the MM BMSCs to secret more cytokines including IL-6,CCL3,CCL4 by activating the JAK-STAT3 pathway, which lead to a amplification of inflammation in BM environment, resulting in the cell proliferation . Disclosures No relevant conflicts of interest to declare.

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