scholarly journals Immunostimulatory Effect of Zanthoxylum schinifolium-Based Complex Oil Prepared by Supercritical Fluid Extraction in Splenocytes and Cyclophosphamide-Induced Immunosuppressed Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Hak Yong Lee ◽  
Young Mi Park ◽  
Yang Hee Lee ◽  
Yang Gyu Kang ◽  
Hyang Man Lee ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cytokine Production ◽  
Nk Cell ◽  
Cell Activity ◽  
Pharmacological Activities ◽  
Inflammatory Cytokine Production ◽  
Immunostimulatory Effect ◽  
Zanthoxylum Schinifolium

Complex oil of Zanthoxylum schinifolium and Perilla frutescens seed (ZPCO) is used as a traditional medicine due to its pharmacological activities. The aim of this study was to investigate the immunostimulatory effect of ZPCO in isolated splenocytes as well as in an immunosuppressed rat model, which was generated via oral administration of cyclophosphamide. Notably, our results showed that ZPCO exerted an immunity-enhancing effect both in vitro and in vivo. Specifically, ZPCO treatment enhanced the viability and inflammatory cytokine production of splenocytes and NK cell activity in vitro. Moreover, this product improved host defense under immunosuppressive conditions by increasing the number of immune cells and promoting the expression of cytokines involved in immune responses. Our results suggest that complex oil including Z. schinifolium should be explored as a novel immunostimulatory agent that could potentially be used for therapeutic purposes or as an ingredient in functional foods.

Differential effects of lactobacilli on activation and maturation of mouse dendritic cells

2014 ◽  
Vol 5 (3) ◽  
pp. 323-334 ◽  
Author(s):  
I. Elawadli ◽  
J.T. Brisbin ◽  
B.A. Mallard ◽  
M.W. Griffiths ◽  
M. Corredig ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Lactic Acid ◽  
Lactic Acid Bacteria ◽  
Immune Responses ◽  
Inflammatory Cytokine ◽  
Cytokine Production ◽  
Lactobacillus Helveticus ◽  
Inflammatory Cytokine Production

Lactic acid bacteria (LAB) are of interest because of their potential to modulate immune responses. The effects of LAB range from regulation to stimulation of the immune system. A series of studies were performed in vitro to study the effects of six lactic acid bacteria (LAB), Lactobacillus helveticus LH-2, Lactobacillus acidophilus La-5, La-115, La-116 and La-14, and Lactobacillus salivarius, on maturation and activation of mouse dendritic cells. Production of tumour necrosis factor (TNF)-?, interleukin (IL)-6 and IL-10 by dendritic cells (DCs) was determined after treating cells with live LAB. The expression of DC maturation markers, CD80 and CD40, was also measured using flow cytometry after stimulation with LAB. In addition, the expression of Toll-like receptors (TLRs) 2, 4 and 9 by DCs stimulated with LAB was measured. Our results revealed that LAB act differentially on pro-inflammatory and anti-inflammatory cytokine production and induction of co-stimulatory molecules by DCs. Specifically, L. salivarius was found to be the most effective LAB to induce pro-inflammatory cytokine production and expression of co-stimulatory molecules. Moreover, La-14, La-116 and La-5 induced moderate maturation and activation of DCs. On the other hand, LH-2 and La-115 were the least effective lactobacilli to induce DC responses. The present study also revealed that L. salivarius was able to induce the expression of TLR2, 4 and 9 by DCs. In conclusion, various strains and species of LAB can differentially regulate DC activation and maturation, providing further evidence that these bacteria may have the ability to influence and steer immune responses in vivo.

In vivo and in vitro effects of fluoroquinolones on lipopolysaccharide-induced pro-inflammatory cytokine production

2009 ◽  
Vol 15 (3) ◽  
pp. 168-173 ◽  
Author(s):  
Hiromi Ogino ◽  
Miho Fujii ◽  
Mariko Ono ◽  
Kayoko Maezawa ◽  
Junko Kizu ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Cytokine Production ◽  
Inflammatory Cytokine Production ◽  
In Vitro Effects

Inflammation restraining effects of prostaglandin E2 on natural killer–dendritic cell (NK-DC) interaction are imprinted during DC maturation

Blood ◽  
2011 ◽  
Vol 118 (9) ◽  
pp. 2473-2482 ◽  
Author(s):  
Catharina H. M. J. Van Elssen ◽  
Joris Vanderlocht ◽  
Tammy Oth ◽  
Birgit L. M. G. Senden-Gijsbers ◽  
Wilfred T. V. Germeraad ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Immune Responses ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
T Helper 1 ◽  
Ifn Γ ◽  
Dc Maturation

Abstract Among prostaglandins (PGs), PGE2 is abundantly expressed in various malignancies and is probably one of many factors promoting tumor growth by inhibiting tumor immune surveillance. In the current study, we report on a novel mechanism by which PGE2 inhibits in vitro natural killer–dendritic cell (NK-DC) crosstalk and thereby innate and adaptive immune responses via its effect on NK-DC crosstalk. The presence of PGE2 during IFN-γ/membrane fraction of Klebsiella pneumoniae DC maturation inhibits the production of chemokines (CCL5, CCL19, and CXCL10) and cytokines (IL-12 and IL-18), which is cAMP-dependent and imprinted during DC maturation. As a consequence, these DCs fail to attract NK cells and show a decreased capacity to trigger NK cell IFN-γ production, which in turn leads to reduced T-helper 1 polarization. In addition, the presence of PGE2 during DC maturation impairs DC-mediated augmentation of NK-cell cytotoxicity. Opposed to their inhibitory effects on peripheral blood–derived NK cells, PGE2 matured DCs induce IL-22 secretion of inflammation constraining NKp44+ NK cells present in mucosa-associated lymphoid tissue. The inhibition of NK-DC interaction is a novel regulatory property of PGE2 that is of possible relevance in dampening immune responses in vivo.

Solannm lyratum extract affected immune response in normal and leukemia murine animal in vivo

2010 ◽  
Vol 29 (5) ◽  
pp. 359-367 ◽  
Author(s):  
Jai-Sing Yang ◽  
Chia-Chun Wu ◽  
Chao-Lin Kuo ◽  
Chin-Chung Yeh ◽  
Fu-Shin Chueh ◽  
...  
Keyword(s):  
Immune Responses ◽  
Mononuclear Cells ◽  
Nk Cell ◽  
Folk Medicine ◽  
Cell Activity ◽  
Colon Adenocarcinoma ◽  
Target Cells ◽  
Peripheral Blood Mononuclear ◽  
Macrophage Phagocytosis

Solanum lyratum Thunberg (Solanaceae) has been used as a folk medicine for treating liver, lung and esophagus in the Chinese population. Our previous studies have shown that the crude extract of S. lyratum Thunberg (SLE) induced apoptosis in colo 205 human colon adenocarcinoma cells; however, there is no report to show SLE affect immune responses in vivo. In this study, the in vivo effects of SLE on leukemia WEHI-3 cells and immune responses such as phagocytosis and natural killer (NK) cell activity in normal and leukemia mice were investigated. The SLE treatment decreases surface markers of CD3 and Mac-3 in normal and leukemia mice but promoted the cell markers of CD19 and CD11b in normal mice and CD11b in leukemia mice indicating that the precursors of T cells was inhibited and B cells and macrophage were promoted. The SLE treatment promoted the activity of macrophage phagocytosis in the peripheral blood mononuclear cells (PBMC) and peritoneal cells from normal and leukemia mice. The results also showed that NK cells from the normal and leukemia mice after treatment with SLE can kill the YAC-1 target cells. Therefore, the SLE treatment increased macrophage and NK cell activities. These consistent results indicate SLE could be a potent immune responses agent.

scholarly journals CD33 Delineates Two Functionally Distinct NK Cell Populations Divergent in Cytokine Production and Antibody-Mediated Cellular Cytotoxicity

2022 ◽  
Vol 12 ◽  
Author(s):  
Maryam Hejazi ◽  
Congcong Zhang ◽  
Sabrina B. Bennstein ◽  
Vera Balz ◽  
Sarah B. Reusing ◽  
...  
Keyword(s):  
Nk Cells ◽  
Cytokine Production ◽  
Nk Cell ◽  
Functional Divergence ◽  
Target Cells ◽  
Cellular Cytotoxicity ◽  
Transcriptional Signature ◽  
Promising Target

The generation and expansion of functionally competent NK cells in vitro is of great interest for their application in immunotherapy of cancer. Since CD33 constitutes a promising target for immunotherapy of myeloid malignancies, NK cells expressing a CD33-specific chimeric antigen receptor (CAR) were generated. Unexpectedly, we noted that CD33-CAR NK cells could not be efficiently expanded in vitro due to a fratricide-like process in which CD33-CAR NK cells killed other CD33-CAR NK cells that had upregulated CD33 in culture. This upregulation was dependent on the stimulation protocol and encompassed up to 50% of NK cells including CD56dim NK cells that do generally not express CD33 in vivo. RNAseq analysis revealed that upregulation of CD33+ NK cells was accompanied by a unique transcriptional signature combining features of canonical CD56bright (CD117high, CD16low) and CD56dim NK cells (high expression of granzyme B and perforin). CD33+ NK cells exhibited significantly higher mobilization of cytotoxic granula and comparable levels of cytotoxicity against different leukemic target cells compared to the CD33− subset. Moreover, CD33+ NK cells showed superior production of IFNγ and TNFα, whereas CD33− NK cells exerted increased antibody-dependent cellular cytotoxicity (ADCC). In summary, the study delineates a novel functional divergence between NK cell subsets upon in vitro stimulation that is marked by CD33 expression. By choosing suitable stimulation protocols, it is possible to preferentially generate CD33+ NK cells combining efficient target cell killing and cytokine production, or alternatively CD33− NK cells, which produce less cytokines but are more efficient in antibody-dependent applications.

scholarly journals Generation of hypoimmunogenic human pluripotent stem cells

2019 ◽  
Vol 116 (21) ◽  
pp. 10441-10446 ◽  
Author(s):  
Xiao Han ◽  
Mengning Wang ◽  
Songwei Duan ◽  
Paul J. Franco ◽  
Jennifer Hyoje-Ryu Kenty ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Therapy ◽  
Immune Responses ◽  
Pluripotent Stem Cells ◽  
Nk Cell ◽  
Immune Surveillance ◽  
Human Pluripotent Stem Cells ◽  
Innate Immune

Polymorphic HLAs form the primary immune barrier to cell therapy. In addition, innate immune surveillance impacts cell engraftment, yet a strategy to control both, adaptive and innate immunity, is lacking. Here we employed multiplex genome editing to specifically ablate the expression of the highly polymorphic HLA-A/-B/-C and HLA class II in human pluripotent stem cells. Furthermore, to prevent innate immune rejection and further suppress adaptive immune responses, we expressed the immunomodulatory factors PD-L1, HLA-G, and the macrophage “don’t-eat me” signal CD47 from the AAVS1 safe harbor locus. Utilizing in vitro and in vivo immunoassays, we found that T cell responses were blunted. Moreover, NK cell killing and macrophage engulfment of our engineered cells were minimal. Our results describe an approach that effectively targets adaptive as well as innate immune responses and may therefore enable cell therapy on a broader scale.

scholarly journals NK-Cell-Mediated Targeting of Various Solid Tumors Using a B7-H3 Tri-Specific Killer Engager In Vitro and In Vivo

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2659 ◽  
Author(s):  
Daniel A. Vallera ◽  
Soldano Ferrone ◽  
Behiye Kodal ◽  
Peter Hinderlie ◽  
Laura Bendzick ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Function ◽  
Nk Cell ◽  
Human Cancer ◽  
Cell Activity ◽  
Antibody Fragment

We improved the bispecific antibody platform that primarily engages natural killer (NK) cells to kill cancer cells through antibody-dependent cellular cytotoxicity (ADCC) by adding IL-15 as a crosslinker that expands and self-sustains the effector NK cell population. The overall goal was to target B7-H3, an established marker predominantly expressed on cancer cells and minimally expressed on normal cells, and prove that it could target cancer cells in vitro and inhibit tumor growth in vivo. The tri-specific killer engager (TriKETM) was assembled by DNA shuffling and ligation using DNA encoding a camelid anti-CD16 antibody fragment, a wild-type IL-15 moiety, and an anti-B7-H3 scFv (clone 376.96). The expressed and purified cam1615B7H3 protein was tested for in vitro NK cell activity against a variety of tumors and in vivo against a tagged human MA-148 ovarian cancer cell line grafted in NSG mice. cam1615B7H3 showed specific NK cell expansion, high killing activity across a range of B7-H3+ carcinomas, and the ability to mediate growth inhibition of aggressive ovarian cancer in vivo. cam1615B7H3 TriKE improves NK cell function, expansion, targeted cytotoxicity against various types of B7-H3-positive human cancer cell lines, and delivers an anti-cancer effect in vivo in a solid tumor setting.

Temporal, Quantitative and Functional Characteristics of Single-KIR Positive Alloreactive NK Cell Recovery Account for Impaired Graft Versus Leukemia Activity after Haploidentical HSCT.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3274-3274
Author(s):  
Luca Vago ◽  
Barbara Forno ◽  
Elisabetta Zino ◽  
Simona Di Terlizzi ◽  
Maria T. Lupo Stanghellini ◽  
...  
Keyword(s):  
Nk Cells ◽  
Nk Cell ◽  
Therapeutic Option ◽  
Flow Cytometric Analysis ◽  
Cell Activity ◽  
Biological Data ◽  
Cell Recovery ◽  
Hematopoietic Stem

Abstract Haploidentical Hematopoietic Stem Cell Transplantation (haplo-HSCT) is a promising therapeutic option for patients lacking a fully compatible donor. Due to extensive T cell depletion, Natural Killer (NK) cell activity represents the only immunological protection against disease relapse for the first months after haplo-HSCT. Clinical studies have associated donor-recipient incompatibility for Human Leukocyte Antigen (HLA) ligands of Killer Immunoglobulin-like Receptors (KIR), with a marked anti-leukemic activity. Alloreactive donor NK cells carrying a single KIR whose ligand is missing in the recipient mediate a potent graft vs. leukemia effect, resulting in reduced incidence of relapse and increased Overall Survival (OS). These exciting results have recently been challenged by conflicting clinical and biological data from different groups. In the present study, we have characterized reconstitution of NK cells, in particular of alloreactive single-KIR+ NK cells, in 58 patients who received CD34+ selected haplo-HSCT for high-risk hematologic malignancies. One month after haplo-HSCT CD56bright/CD56dim NK cell subsets were subverted in their proportions and phenotypic features, accounting for enrichment in maturation intermediates. We show that CD25 and CD117 deregulation by CD56bright, and NKG2A and CD62L by CD56dim, are intrinsic to NK cell physiologic differentiation and support a sequential CD56bright-to-CD56dim NK cell maturation. Consistently, the in vitro functional potential of these maturation intermediates against leukemic blasts was heavily impaired, both in terms of cytotoxicity and of cytokine release. Full mature receptor repertoire reconstitution took at least three months. Alloreactive single-KIR+ NK cells had highly variable frequency ranging from less than 1% to more than 30% of NK cells circulating at 90–120 days after transplantation, independently from predicted NK alloreactivity. Importantly, out of three patients with predicted NK alloreactivity, none had a relative expansion of alloreactive single-KIR+ cells, accounting for less than 1% of circulating NK cells in two of them. As demonstrated by flow cytometric analysis of NK cell CD107a mobilization in response to the HLA class I negative target 721.221, single-KIR+ NK cells at three months after haplo-HSCT showed a not yet fully developed functional reactivity, which was recovered to donor-levels only at later time-points. In line with these observations, clinical outcome of haplo-HSCT was not affected in any way by the presence of donor NK alloreactivity. The incidence of relapse was virtually identical in patients transplanted from alloreactive or non-alloreactive donors. Taken together, our data shed new light onto the kinetics of NK cell differentiation in vivo and suggest that NK alloreactivity could be best exploited by the use of mature donor single-KIR+ selected alloreactive NK cells.

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