Vandellia Cordifolia Regulated Cell Proliferation and Cytokines Production in Human Mononuclear Cells

2000 ◽  
Vol 28 (03n04) ◽  
pp. 313-323 ◽  
Author(s):  
An-Pang Lin ◽  
Wei-Jern Tsai ◽  
Chi-Yen Fan ◽  
Ming-Jen Lee ◽  
Yuh-Chi Kuo
Keyword(s):  
Cell Cycle Progression ◽  
Mononuclear Cells ◽  
Tritiated Thymidine ◽  
Interleukin 2 ◽  
Interferon Γ ◽  
Thymidine Uptake ◽  
Dependent Manner ◽  
Human Mononuclear Cells ◽  
Tritiated Thymidine Uptake ◽  
Ifn Γ

Vandellia cordifolia (V. cordifolia) used for treatment inflammation in traditional Chinese medicine was selected for immunopharmacological activity test. The effects of V. cordifolia extracted fractions on human mononuclear cells (HMNC) proliferation were determined by tritiated thymidine uptake. The results indicated that VC-ME fraction suppressed HMNC proliferation activated with phytohemagglutinin (PHA) and stimulated cell cycle progression was arrested at the G0/G1 stage. The inhibitory mechanisms may involve the blocking of interleukin-2 (IL-2) and interferon-γ (IFN-γ) production, since VC-ME suppressed IL-2 and IFN-γ production of HMNC in a dose-dependent manner. Therefore, it is suggested that immunomodulatory agents are contained in V. cordifolia.

scholarly journals Alloimmune Monitoring after Islet Transplantation: A Prospective Multicenter Assessment of 25 Recipients

2016 ◽  
Vol 25 (12) ◽  
pp. 2259-2268 ◽  
Author(s):  
Vaihere Delaune ◽  
Christian Toso ◽  
Pierre-Yves Benhamou ◽  
Anne Wojtusciszyn ◽  
Laurence Kessler ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Islet Transplantation ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Graft Function ◽  
Area Under The Curve ◽  
Interferon Γ ◽  
Ki 67 ◽  
Peripheral Blood Mononuclear ◽  
Ifn Γ

Islet transplantation is an effective treatment for selected patients with type 1 diabetes. However, an accurate test still lacks for the early detection of graft rejection. Blood samples were prospectively collected in four university centers (Geneva, Grenoble, Montpellier, and Strasbourg). Peripheral blood mononuclear cells were stimulated with donor splenocytes in the presence of interleukin-2. After 24 h of incubation, interferon-γ (IFN-γ) ELISpot analysis was performed. After a total of 5 days of incubation, cell proliferation was assessed by fluorescence-activated cell sorting (FACS) analysis for Ki-67. Immunological events were correlated with adverse metabolic events determined by loss of ≥1 point of β-score and/or an increased insulin intake ≥10%. Twenty-five patients were analyzed; 14 were recipients of islets alone, and 11 combined with kidney. Overall, 76% (19/25) reached insulin independence at one point during a mean follow-up of 30.7 months. IFN-γ ELISpot showed no detectable correlation with adverse metabolic events [area under the curve (AUC) = 0.57]. Similarly, cell proliferation analysis showed no detectable correlation with adverse metabolic events (CD3+/ CD4+ AUC = 0.54; CD3+/CD8+ AUC = 0.55; CD3-/CD56+ AUC = 0.50). CD3-/CD56+ cell proliferation was significantly higher in patients with combined kidney transplantation versus islet alone (6 months, p = 0.010; 12 months, p = 0.016; and 24 months, p = 0.018). Donor antigen-stimulated IFN-γ production and cell proliferation do not predict adverse metabolic events after islet transplantation. This suggests that the volume of transplanted islets is too small to produce a detectable systemic immune response and/or that alloimmune rejection is not the sole reason for the loss of islet graft function.

High production of interferon γ but not interleukin-2 by human T-lymphotropic virus type I–infected peripheral blood mononuclear cells

Blood ◽  
2001 ◽  
Vol 98 (3) ◽  
pp. 721-726 ◽  
Author(s):  
Emmanuel Hanon ◽  
Peter Goon ◽  
Graham P. Taylor ◽  
Hitoshi Hasegawa ◽  
Yuetsu Tanaka ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Interferon Γ ◽  
Type I ◽  
Peripheral Blood Mononuclear ◽  
T Lymphotropic Virus ◽  
Blood Mononuclear Cells ◽  
Ifn Γ

Abstract The transactivator protein of human T-lymphotropic virus I (HTLV-I), Tax, has been associated with the up-regulation of several host cell genes, including interleukin 2 (IL-2), the IL-2 receptor-α(IL-2Rα) chain (CD25), interferon γ(IFN-γ), and tumor necrosis factor (TNF). It has been proposed that an IL-2/CD25 autocrine loop plays a part in maintaining the very high proviral loads often found in HTLV-I infection. Furthermore, abnormal production of inflammatory cytokines might contribute to the pathogenesis of the inflammatory diseases associated with HTLV-I infection. However, there has been no study of the expression of these genes in freshly isolated peripheral blood mononuclear cells (PBMCs) naturally infected with HTLV-I. In the present study, flow cytometry was used to determine which cytokines are produced by freshly isolated PBMCs that spontaneously express the HTLV-I Tax protein. Surprisingly, the results show that intracellular Tax expression is associated with rapid up-regulation of IFN-γ but not TNF or IL-2. A proportion of HTLV-I–infected cells express both IFN-γ and the surface markers of effector memory cells. Such cells are capable of migration through peripheral tissues and could therefore contribute to the inflammation seen in diseases such as HTLV-I–associated myelopathy/tropical spastic paraparesis.

scholarly journals Effect of Steroids on Lipopolysaccharide/Interleukin 2-Induced Interleukin 18 Production in Peripheral Blood Mononuclear Cells

2002 ◽  
Vol 30 (2) ◽  
pp. 144-160 ◽  
Author(s):  
M Kodama ◽  
HK Takahashi ◽  
H Iwagaki ◽  
H Itoh ◽  
T Morichika ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Steroid Treatment ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Enhanced Production ◽  
Blood Mononuclear Cells ◽  
Ifn Γ ◽  
Cytokine Cascade

Interleukin (IL) 18, a powerful inducer of the immunoregulatory cytokine interferon-γ (IFN-γ), presents upstream of the cytokine activation cascade in the inflammatory response. The anti-inflammatory properties of steroids permit their use in various conditions, although effects are transient and pathological states are not fully relieved by short-term steroidal use. We examined the effect of lipopolysaccharide (LPS)/IL-2 on the cytokine cascade in human peripheral blood mononuclear cells (PBMCs). We also examined the effect of steroids on LPS/IL-2-induced cytokine production in human PBMCs taken from healthy volunteers. Cell-free supernatant fractions were assayed for IL-18, IL-12, IL-2, IFN-γ and IL-10 protein, using enzyme-linked immunosorbent assays, and synergy between LPS and IL-2 in enhanced production of IL-18 was observed. Steroids suppressed the production of IL-18 and other secondary cytokines in LPS/IL-2-stimulated PBMCs, in a concentration- and time-dependent manner, although inhibition was incomplete even at high concentrations. Effects of steroid treatment on expression of membrane-bound LPS receptor antigen (mCD14) and intercellular adhesion molecule-1 (ICAM-1) in PBMCs were studied by flow cytometric analysis. Steroid treatment up-regulated mCD14 expression in a concentration-dependent manner, with no effect on ICAM-1 expression. These results suggest that the incomplete counteraction of steroids in the LPS/IL-2-initiating cytokine cascade is due, at least partly, to the up-regulation of mCD14 by steroid preparations, which increases susceptibility to bacterial endotoxins.

Interleukin 6 stimulates growth of vascular smooth muscle cells in a PDGF-dependent manner

1991 ◽  
Vol 260 (5) ◽  
pp. H1713-H1717 ◽  
Author(s):  
U. Ikeda ◽  
M. Ikeda ◽  
T. Oohara ◽  
A. Oguchi ◽  
T. Kamitani ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Interleukin 6 ◽  
Thymidine Incorporation ◽  
Tritiated Thymidine ◽  
Muscle Cells ◽  
Thymidine Uptake ◽  
Dependent Manner

We have investigated the effect of interleukin 6 (IL-6) on the growth of vascular smooth muscle cells (VSMC) isolated from rat aortas. Murine recombinant IL-6 significantly increased the number of VSMC and stimulated tritiated thymidine incorporation into VSMC in a dose-dependent manner. The IL-6-induced thymidine incorporation into VSMC was totally inhibited by the Ca2+ channel blocker verapamil; however, IL-6 showed no effects on the intracellular Ca2+ level ([Ca2+]i) in VSMC. Antibody against platelet-derived growth factor (PDGF) also totally inhibited the IL-6-induced thymidine uptake. PDGF caused a significant increase in the [Ca2+]i, which was totally inhibited by verapamil. IL-6 mRNA was not detected in unstimulated “quiescent” VSMC, but its expression was stimulated by exposure of VSMC to 10% fetal bovine serum. Immunohistochemical study using anti-PDGF antibody showed that IL-6 stimulated PDGF production in VSMC. These results support the premise that IL-6 is released by VSMC in an autocrine manner and promotes the growth of VSMC via induction of endogenous PDGF production.

scholarly journals Effect ofTityus serrulatusvenom on cytokine production and the activity of murine macrophages

2002 ◽  
Vol 11 (1) ◽  
pp. 23-31 ◽  
Author(s):  
Vera L. Petricevich
Keyword(s):  
Cytokine Production ◽  
Peritoneal Macrophages ◽  
Interferon Γ ◽  
Enzyme Linked Immunosorbent Assay ◽  
No Production ◽  
Dependent Manner ◽  
Immune Functions ◽  
Macrophage Activity ◽  
Ifn Γ

The purpose of this study was to investigate the effects ofTityus serrulatusvenom (TSV) on murine peritoneal macrophages evaluated in terms of activation. The effects of crude TSV were analysed by detection of cytokines, oxygen intermediate metabolites (H2O2) and nitric oxide (NO) in supernatants of peritoneal macrophages. Several functional bioassays were employed including anin vitromodel for envenomating: cytotoxicity of TSV was assessed using the lyses percentage. Tumor necrosis factor (TNF) activity was assayed by measuring its cytotoxic activity on L-929 cells, and interleukin-6 (IL-6) and interferon-γ (IFN-γ) were assayed by enzyme-linked immunosorbent assay, whereas NO levels were detected by Griess colorimetric reactions in culture supernatant of macrophages incubated with TSV and subsequently exposed to either lipopolysaccharide or IFN-γ. Incubation of macrophages with TSV increased production of IL-6 and IFN-γ in a dose-dependent manner. TNF production was not detected in supernatants treated with TSV at any concentration. The increase in IL-6 secretion was not associated with concentration-dependent cytoxicity of TSV on these cells. These data suggest that the cytotoxicity does not appear to be the main cause of an increased cytokine production by these cells. Although NO is an important effector molecule in macrophage microbicidal activity, the inducing potential of the test compounds for its release was found to be very moderate, ranging from 125 to 800 mM. Interestingly, NO levels of peritoneal macrophages were increased after IFN-γ. Moreover, NO production had an apparent effect on macrophage activity. The results obtained here also shown that the TSV induces an important elevation in H2O2release. These results combined with NO production suggest that TSV possesses significant immunomodulatory activities capable of stimulating immune functionsin vitro.

Prolonged survival of mice with glioma injected intracerebrally with double cytokine—secreting cells

1995 ◽  
Vol 83 (6) ◽  
pp. 1038-1044 ◽  
Author(s):  
Terry Lichtor ◽  
Roberta P. Glick ◽  
Tae Sung Kim ◽  
Roger Hand ◽  
Edward P. Cohen
Keyword(s):  
Cell Line ◽  
Interleukin 2 ◽  
Glioma Cells ◽  
Fibroblast Cell ◽  
Interferon Γ ◽  
Glioma Cell Line ◽  
Mouse Fibroblast ◽  
Spleen Cells ◽  
Content Type ◽  
Ifn Γ

✓ A novel approach toward the treatment of glioma was developed in a murine model. The genes for both interleukin-2 (IL-2) and interferon-γ (IFN-γ) were first transfected into a mouse fibroblast cell line that expresses defined major histocompatibility complex (MHC) determinants (H—2k). The double cytokine—secreting cells were then cotransplanted intracerebrally with the Gl261 murine glioma cell line into syngeneic C57BL/6 mice (H—2b) whose cells differed at the MHC from the cellular immunogen. The results indicate that the survival of mice with glioma injected with the cytokine-secreting allogeneic cells was significantly prolonged, relative to the survival of mice receiving equivalent numbers of glioma cells alone. Using a standard 51Cr-release assay, the specific release of isotope from labeled Gl261 cells coincubated with spleen cells from mice injected intracerebrally with the glioma cells and the cytokine-secreting fibroblasts was significantly higher than the release of isotope from glioma cells coincubated with spleen cells from nonimmunized mice. The cellular antiglioma response was mediated by natural killer/lymphokine-activated killer and Lyt-2.2+ (CD8+) cells. The increased survival of mice with glioma and the specific immunocytotoxic responses after immunization with fibroblasts modified to secrete both IL-2 and IFN-γ indicate the potential of an immunotherapeutic approach to gliomas with cytokine-secreting cells.

scholarly journals Hemodialysis-Related Lymphomononuclear Release of Interleukin-12 in Patients with End-Stage Renal Disease

1999 ◽  
Vol 10 (10) ◽  
pp. 2171-2176 ◽  
Author(s):  
BRUNO MEMOLI ◽  
LUIGI MARZANO ◽  
VINCENZO BISESTI ◽  
MICHELE ANDREUCCI ◽  
BRUNA GUIDA
Keyword(s):  
Mononuclear Cells ◽  
Interferon Γ ◽  
Interleukin 12 ◽  
Control Group ◽  
Peripheral Blood Mononuclear ◽  
Mitogen Stimulation ◽  
Ifn Γ ◽  
Uremic Patients ◽  
Stage Renal Disease ◽  
End Stage

Abstract. Interleukin-12 (IL-12) is a cytokine produced by peripheral blood mononuclear cells (PBMC) that causes interferon-γ (IFN-γ) production and enhancement of cell-mediated cytotoxicity. To clarify the role of hemodialysis biocompatibility on IL-12 production and uremic immunodeficiency, we have studied the IL-12 and IFN-γ release by PBMC harvested from 12 patients dialyzed with cuprophan membrane (CU), eight patients dialyzed with polymethylmethacrylate membrane (PMMA), and eight nondialyzed uremic patients (UR). Ten healthy subjects constituted the control group (CON). PBMC were cultured for 48 h with and without nonspecific mitogen stimulation. In unstimulated conditions, CU showed an IL-12 PBMC production higher than CON, UR, and PMMA (46.67 ± 30.13versus2.56 ± 1.38, 6.16 ± 7.09, and 4.62 ± 4.76 pg/ml, respectively;P< 0.01). IL-12 production was correlated with C3a concentration measured at the outlet of hemodialyzer after 15 min of dialysis (r= 0.69,P< 0.01). IL-12 release in CU remained unchanged under mitogen stimulation (44.34 ± 23.86 pg/ml) and was lower than in CON, UR, and PMMA (66.0 ± 12.41, 68.37 ± 25.78, and 67.75 ± 22.61 pg/ml, respectively;P< 0.05). IFN-γ production was similar, in unstimulated conditions, in all groups. Under stimulation, IFN-γ release was lower in CU (13.42 ± 12.04 IU/ml) than in CON, UR, and PMMA (51.84 ± 30.74, 32.16 ± 13.86, and 32.16 ± 13.86 IU/ml, respectively;P< 0.01). These results demonstrate that hemodialysis with CU induces monocyte activation with an enhanced release of IL-12. On the contrary, stimulated PBMC production of both IL-12 and IFN-γ is lower in these patients than in CON, UR, and PMMA. The altered release of these cytokines could play a role in cell-mediated immunodeficiency of the uremic patients dialyzed with CU.

scholarly journals Spontaneous secretion of interferon γ and interleukin 4 by human intraepithelial and lamina propria gut lymphocytes

Gut ◽  
1998 ◽  
Vol 42 (5) ◽  
pp. 643-649 ◽  
Author(s):  
M Carol ◽  
A Lambrechts ◽  
A Van Gossum ◽  
M Libin ◽  
M Goldman ◽  
...  
Keyword(s):  
Lamina Propria ◽  
Intestinal Mucosa ◽  
Mononuclear Cells ◽  
Critical Role ◽  
Gastrointestinal Diseases ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Peripheral Blood Mononuclear ◽  
Ifn Γ

Background—Cytokines secreted by intestinal T lymphocytes probably play a critical role in regulation of the gut associated immune responses.Aims—To quantify interferon γ (IFN-γ) and interleukin 4 (IL-4) secreting cells (SC) among human intraepithelial (IEL) and lamina propria (LPL) lymphocytes from the duodenum and right colon in non-pathological situations and in the absence of in vitro stimulation.Patients—Duodenal and right colonic biopsy specimens were obtained from patients with no inflammation of the intestinal mucosa.Methods—Intraepithelial and lamina propria cell suspensions were assayed for numbers of cells spontaneously secreting IFN-γ and IL-4 by a two site reverse enzyme linked immunospot technique (ELISPOT).Results—The relatively high proportion of duodenal lymphocytes spontaneously secreting IFN-γ (IEL 3.6%; LPL 1.9%) and IL-4 (IEL 1.3%; LPL 0.7%) contrasted with the very low numbers of spontaneously IFN-γ SC and the absence of spontaneously IL-4 SC among peripheral blood mononuclear cells. In the basal state, both IFN-γ and IL-4 were mainly produced by CD4+ cells. Within the colon, only 0.2% of IEL and LPL secreted IFN-γ in the basal state, and 0.1% secreted IL-4.Conclusions—Compared with peripheral lymphocytes substantial proportions of intestinal epithelial and lamina propria lymphocytes spontaneously secrete IFN-γ and/or IL-4. These cytokines are probably involved in the normal homoeostasis of the human intestinal mucosa. Disturbances in their secretion could play a role in the pathogenesis of gastrointestinal diseases.

scholarly journals Polarization of Allogeneic T-Cell Responses by Influenza Virus-Infected Dendritic Cells

2000 ◽  
Vol 74 (17) ◽  
pp. 7738-7744 ◽  
Author(s):  
Sangkon Oh ◽  
Maryna C. Eichelberger
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
Influenza Virus ◽  
T Cell ◽  
Interleukin 2 ◽  
Dependent Manner ◽  
Ifn Γ ◽  
High Doses ◽  
Type Response

ABSTRACT The developing immune response in the lymph nodes of mice infected with influenza virus has both Th1- and Th2-type characteristics. Modulation of the interactions between antigen-presenting cells and T cells is one mechanism that may alter the quality of the immune response. We have previously shown that the ability of dendritic cells (DC) to stimulate the proliferation of alloreactive T cells is changed by influenza virus due to viral neuraminidase (NA) activity. Here we show that DC infected with influenza virus A/PR/8/34 (PR8) stimulate T cells to produce different types of cytokines in a dose-dependent manner. Optimal amounts of the Th1-type cytokines interleukin-2 (IL-2) and gamma interferon (IFN-γ) were produced from T cells stimulated by DC infected with low doses of PR8, while the Th2-type cytokines IL-4 and IL-10 were produced only in response to DC infected with high doses of PR8. IL-2 and IFN-γ levels corresponded with T-cell proliferation and were dependent on the activity of viral NA on the DC surface. In contrast, IL-4 secretion required the treatment of T cells with NA. Since viral particles were released only from DC that are infected with high doses of PR8, our results suggest that viral NA on newly formed virus particles desialylates T-cell surface molecules to facilitate a Th2-type response. These results suggest that the activity of NA may contribute to the mixed Th-type response observed during influenza virus infection.

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