The flavonoid Kaempferol suppresses the graft-versus-host reaction by inhibiting type 1 cytokine production and CD8+ T cell engraftment.

We have here examined the immunoregulatory effects of a natural flavonoid, Kaempferol, on T cells. Kaempferol suppressed IFN-gamma and IL-2 production but not that of IL-4 by T cells and shifted the Th1/Th2 balance into the Th2 phenotype. In C57BL/6 anti-BDF1 MLC, Kaempferol inhibited the development and expansion of type 1 effector CD8+ T cells and diminished allospecific CTL activity.

Trehalose augments osteoprotegerin production in the FHs74Int human intestinal epithelial cell line.

The disaccharide trehalose has been shown to inhibit both bone loss in ovariectomized mice and excessive osteoclastogenesis in lipopolysaccharide-injected mice. However, the mechanism of osteoclastogenesis inhibition by oral administration of trehalose is still unclear. We report here for the first time that a human intestinal epithelial cell line, FHs74Int, also produces osteoprotegerin (OPG) and that trehalose augments OPG production by this cell line.

The natural plant product tryptanthrin ameliorates dextran sodium sulfate-induced colitis in mice.

The therapeutic effects of tryptanthrin (TRYP), a natural product from the medicinal plant Polygonum tinctorium, were examined in a murine model of inflammatory bowel disease (IBD). Colitis was induced by 5% dextran sodium sulfate (DSS) in drinking water for 7 days from day 0. TRYP (100 mg/kg) was administered orally suspended in 5% arabia gum everyday from day 3 for 5 days.

Prevention of azoxymethane-induced intestinal tumors by a crude ethyl acetate-extract and tryptanthrin extracted from Polygonum tinctorium Lour.

The effect of a crude ethyl acetate (AcOEt)-extract and tryptanthrin extracted from the Indigo plant (Polygonum tinctorium Lour.) on azoxymethane (AOM)-induced intestinal tumors was examined in F344 rats. The rats were given subcutaneous (s.

Characterization of the antitumor activities of IFN-alpha8 on renal cell carcinoma cells in vitro.

Interferon-alpha (IFN-alpha) has a number of therapeutic applications in the treatment of various human cancers and diseases of viral origin. IFN-alpha includes several subtypes, and little has been reported on the biologic properties of the individual subtypes. Here, we report on the individual antitumor effects of five IFN-alpha subtypes, alpha1, alpha2, alpha5, alpha8, and alpha10, against six renal cell carcinoma (RCC) cell lines in vitro.

Preventive effect of Coriandrum sativum (Chinese parsley) on localized lead deposition in ICR mice.

The preventive effect of Coriandrum sativum, Fam. UMBELLIFERAE (Chinese parsley) on lead deposition was investigated in male ICR mice given lead (1000 ppm) as lead acetate trihydrate in drinking water for 32 days. Administration of Chinese parsley to mice by gastric intubation was performed for 25 days from day 7 after the start of lead exposure up to the end of the experiment.

Trehalose suppresses lipopolysaccharide-induced osteoclastogenesis bone marrow in mice.

We have previously shown that trehalose suppresses bone loss in ovariectomized (OVX) mice by way of inhibiting osteoclast differentiation in bone marrow. Also, trehalose inhibits the secretion of interleukin-6 in bone marrow cell cultures, resulting in a decrease in osteoclast formation. In this study, we examined the effect of trehalose on osteoclastogenesis using another model of bone resorption, namely lipopolysaccharide (LPS)-stimulated osteoclast induction.

Cell differentiation and apoptosis of monocytic and promyelocytic leukemia cells (U-937 and HL-60) by tryptanthrin, an active ingredient of Polygonum tinctorium Lour.

Tryptanthrin, a bioactive ingredient of Polygonum tinctorium Lour., is a member of the Indigo plant family and has potent cytocidal effects on various human leukemia cells in vitro. At low concentrations, tryptanthrin enhanced the expression of cell differentiation (CD) markers in human monocytic (U-937) and promyelocytic (HL-60) leukemia cells indicative of differentiation to monocytes/macrophages.

Pulmonary carcinogenesis induced by ferric nitrilotriacetate in mice and protection from it by Brazilian propolis and artepillin C.

In experiments using the renal carcinogen ferric nitrilotriacetate (Fe-NTA) in male ddY mice, primary pulmonary cancers were also induced in bronchiolar and alveolar tissues. 4-Hydroxy-2-nonenal (4-HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), products of oxidative processes, increased in bronchiolar and alveolar cells after administration of Fe-NTA. These substances disappeared after oral administration of propolis or artepillin C, as shown histochemically, and correlated with an anticancer prophylactic effect of propolis and artepillin C.

Apoptosis of human leukemia cells induced by Artepillin C, an active ingredient of Brazilian propolis.

Artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) is an active ingredient of Brazilian propolis that possesses anti-tumor activity. When Artepillin C was applied to human leukemia cell lines of different phenotypes, namely, lymphocytic leukemia (7 cell lines of T-cell, 5 cell lines of B-cell), myeloid and monocytic leukemia and non-lymphoid non-myeloid leukemia cell lines in vitro, Artepillin C exhibited potent cytocidal effects and induced marked levels of apoptosis in all the cell lines. The most potent effects were observed in the T-cell lines.

Antibacterial action of tryptanthrin and kaempferol, isolated from the indigo plant (Polygonum tinctorium Lour.), against Helicobacter pylori-infected Mongolian gerbils.

We evaluated the effect of tryptanthrin and kaempferol, both isolated from Polygonum tinctorium Lour., against Helicobacter pylori colony formation in vitro and in H. pylori-infected Mongolian gerbils.

Indirubin inhibits inflammatory reactions in delayed-type hypersensitivity.

Polygonum tinctorium Lour. (P. tinctorium) is known to have the ability to suppress inflammation.

Induction of the activity of the histamine-forming enzyme, histidine decarboxylase, in mice by IL-18 and by IL-18 plus IL-12.

Objective And Design: IL-18 shares functional properties with IL-12, which induces an elevation of histidine decarboxylase (HDC) activity in mouse tissues. Therefore, we examined the effects of IL-18 and IL-18+IL-12 on HDC activity.

Methods: IL-18, IL-12 or IL-18+IL-12 was intraperitoneally injected into BALB/c and C3H/HeN mice and their HDC activities were measured.

Deficient Th1-type immune responses via impaired CD28 signaling in ultraviolet B-induced systemic immunosuppression and the restorative effect of IL-12.

A single large dose (15 kJ/m(2)) of UVB-irradiation induces systemic immunosuppression and tolerance. We previously reported that IL-12 promotes the accessory cell function of epidermal Langerhans cells. In this study we have examined whether IL-12-pretreated antigen-presenting cells (APC) could restore the diminished T-cell response in mice irradiated with a single large dose of UVB.

Tryptanthrin inhibits nitric oxide and prostaglandin E(2) synthesis by murine macrophages.

Nitric oxide (NO) and prostaglandins have been implicated in the pathogenesis of several inflammatory diseases. In this study, we investigated the effect of tryptanthrin (6,12-dihydro-6, 12-dioxoindolo-(2,1-b)-quinazoline), an antimicrobial and antitumoral plant compound isolated from Porigonum tinctorium, on NO and prostaglandin E(2) production by interferon-gamma and lipopolysaccharide-stimulated murine macrophage-like RAW 264.7 cells.

Renal carcinogenesis induced by ferric nitrilotriacetate in mice, and protection from it by Brazilian propolis and artepillin C.

The protective effect of Brazilian propolis and its extract Artepillin C against ferric nitrilotriacetate (Fe-NTA)-induced renal lipid peroxidation and carcinogenesis was studied in male ddY mice. Fe-NTA-induced renal lipid peroxidation leads to a high incidence of renal cell carcinoma (RCC) in mice. Administration of propolis by gastric intubation 2 h before or Artepillin C at either the same time, 2 h, or 5 h before the intraperitoneal injection of Fe-NTA (7 mg Fe/kg) effectively inhibited renal lipid peroxidation.

Interleukin 18 induces a synergistic enhancement of interferon gamma production in mixed murine spleen cell-tumor cell cultures: role of endogenous interleukin 12.

Interleukin 18 (IL-18) reportedly synergizes with IL-12 and IL-10 for interferon gamma (IFN-gamma) synthesis and natural killer (NK) cell activity, respectively. Here we show that IL-18 alone induces low level IFN-gamma production by unstimulated Balb/c mouse spleen cells, but production is enhanced synergistically in cocultures of spleen cells and allogeneic living or fixed Yac-1 cells. Spleen cells could be primed with IL-18 prior to coculture with Yac-1 cells for IFN-gamma production, which also was observed in cocultures containing either syngeneic or xenogeneic tumor cells.

Polygonum tinctorium extract suppresses nitric oxide production by activated macrophages through inhibiting inducible nitric oxide synthase expression.

Despite its beneficial role in host defense mechanisms, excessive nitric oxide (NO) production by activated macrophages has been implicated in several inflammatory diseases. To clarify the mechanisms of anti-inflammatory activities of Polygonum tinctorium, we evaluated whether extracts of P. tinctorium could modulate the production of NO by activated macrophages.

Autocrine interferon-beta stimulation augments nitric oxide production by mouse macrophage J774A.1 cells infected with herpes simplex virus type 1.

The pathogenic roles of nitric oxide (NO) in mouse models have been reported for herpes simplex virus type 1 (HSV-1)-induced pneumonia as well as endotoxin shock. We compared the mechanism of NO production induced by HSV-1 with that induced by lipopolysaccharide (LPS) using a mouse macrophage cell line, J774A.1.

IL-18 prevents the development of chronic graft-versus-host disease in mice.

The development of chronic graft-versus-host disease (GVHD), which is induced by the transfer of DBA/2 spleen cells into (C57BL/6 x DBA/2)F1 (BDF1) mice, is closely related to diminished donor anti-host CTL activity and host B cell hyperactivation. Therefore, an approach which activates donor CD8+ T cells or suppresses donor CD4+ T cell-host B cell interaction may have clinical utility in the treatment of chronic GVHD. We have previously demonstrated that IL-18 induces the development of naive CD8+ T cells into type I effector cells in DBA/2 anti-BDF1 MLC.

Interleukin-18 in combination with IL-2 enhances natural killer cell activity without inducing large amounts of IFN-gamma in vivo.

Interleukin-18 (IL-18) is known to synergistically enhance murine natural killer (NK) cell activity in vitro when combined with either IL-12 or IL-2. However, it has also been demonstrated that simultaneous administration of IL-18 and IL-12 to mice induces extraordinarily large amounts of interferon-gamma (IFN-gamma) in the serum. In this study, we examined the effects of a combination of IL-18 and IL-2 on in vivo NK cell activation in parallel with the induction of toxicity.

IFN-gamma-dependent and -independent mechanisms in adverse effects caused by concomitant administration of IL-18 and IL-12.

IL-18 is a new type of inflammatory cytokine similar to but distinct from IL-12 and IL-1beta. One intriguing property of IL-18 is synergism with IL-12 in many respects. In this study we examined the in vivo synergistic effects of IL-18/IL-12 in mice and found lethal toxicity accompanying an elevated IFN-gamma level in the serum.

Interleukin-18 induces interferon-gamma production through NF-kappaB and NFAT activation in murine T helper type 1 cells.

Interleukin-18 (IL-18) combined with anti-CD3 monoclonal antibody (mAb) induced interferon-gamma (IFN-gamma) production by T helper type 1 (Th1) cells. Neither IL-18 nor anti-CD3 mAb alone induced production of IFN-gamma. Although treatment with IL-18 alone induced full activation of NF-kappaB in Th1 cells, it was not sufficient for the production of IFN-gamma.

Effects of oral administration of interferon-alpha on antibody production in mice with induced tolerance.

In vivo systemic effects and the immunomodulating potential of the oral administration of murine interferon-alpha (IFN-alpha) were investigated through mRNA expression of both IFN-alpha-inducible factors, interferon regulatory factor-1 (IRF-1) and 2,5-adenylate synthetase [2-5(A) synthetase] and 2-5(A) synthetase enzymatic activity in spleen and antibody production. The daily administration of IFN-alpha (0.1, 1, 10, and 100 IU/body) for 1 week augmented IRF-1 and 2-5(A) synthetase mRNA expression levels, as well as 2-5(A) synthetase enzymatic activity in spleen cells but not in cervical lymph nodes.

Oral use of interferon-alpha delays the onset of insulin-dependent diabetes mellitus in nonobese diabetes mice.

Insulin-dependent diabetes mellitus (IDDM) in the nonobese diabetes (NOD) mouse model is thought to be an autoimmune CD4 Th1-like cell-mediated disease. We tested the efficacy of oral use of interferon-alpha (IFN-alpha) therapy on IDDM in NOD mice. Using urine and blood sugar levels as indicators of IDDM, oral administration of murine IFN-alpha (100 IU/body) to NOD mice significantly delayed the onset of symptomatic diabetes.