Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Feline immunodeficiency virus (FIV) infection is characterized by chronic overactivation of immune and inflammatory system, resulting in anergic state and dysfunction of immune cells. Lactoferrin (LF), a glycoprotein present in exocrine secretions and neutrophils, plays an important role in host defense system. Our previous study showed that oral administration of bovine LF (bLF) suppressed oral inflammation, improved the clinical symptoms and decreased serum gamma-globulin as a marker of inflammation in FIV-infected cats with intractable stomatitis. The anti-inflammatory effect was partly involved in regulation of neutrophil function by bLF. In this study, to clarify the relationship between anti-inflammatory effects of bLF and peripheral blood mononuclear cells (PBMC), we examined the effect of bLF on proliferation, cell cycle progression and cytokine expression in mitogen-activated PBMC. MTT [3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl tetrazolium bromide] assay showed that bLF inhibited the concanavalin A (ConA)-induced cell proliferation in FIV-infected cats with the asymptomatic carrier and AIDS-related complex (ARC) phase. Bovine LF restored ConA-induced cell cycle progression and resulted in suppression of the induced apoptosis in feline PBMC. Real-time RT-PCR showed that bLF suppressed ConA-induced expression of interferon-gamma and interleukin-2 in cells of the ARC group regardless of the time of its addition to the medium. These results suggest the hypothesis that therapy with bLF may have the potential to improve and protect functions of overactivated lymphocytes by modulating the cell proliferation, cell cycle and cytokines expression in cats in terminal stage of FIV infection.
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PMID:Effect of bovine lactoferrin on functions of activated feline peripheral blood mononuclear cells during chronic feline immunodeficiency virus infection. 1852 62

The interferon (IFN)-related cytokine interleukin (IL)-29 (also known as IFN-lambda1) inhibits virus replication by inducing a cellular antiviral response similar to that activated by IFN-alpha/beta. However, because it binds to a unique receptor, this cytokine may function cooperatively with IFN-alpha/beta or IFN-gamma during natural infections to inhibit virus replication, and might also be useful therapeutically in combination with other cytokines to treat chronic viral infections such as hepatitis C (HCV). We therefore investigated the ability of IL-29 and IFN-alpha or IFN-gamma to cooperatively inhibit virus replication and induce antiviral gene expression. Compared with the individual cytokines alone, the combination of IL-29 with IFN-alpha or IFN-gamma was more effective at blocking vesicular stomatitis virus and HCV replication, and this cooperative antiviral activity correlated with the magnitude of induced antiviral gene expression. Although the combined effects of IL-29 and IFN-alpha were primarily additive, the IL-29/IFN-gamma combination synergistically induced multiple genes and had the greatest antiviral activity. Two different mechanisms contributed to the enhanced gene expression induced by the cytokine combinations: increased activation of ISRE promoter elements and simultaneous activation of both ISRE and GAS elements within the same promoter. These findings provide new insight into the coregulation of a critical innate immune response by functionally distinct cytokine families.
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PMID:Interleukin-29 functions cooperatively with interferon to induce antiviral gene expression and inhibit hepatitis C virus replication. 1875 65

Extracts of Scutellaria baicalensis display a wide spectrum of antiviral activity. It was of great interest to check the effect of baicalein and wogonin preparations on two important mechanisms of innate immunity: the secretion of cytokines and the natural resistance of human leukocytes to viral infection. To study the effect of S. baicalensis extracts on interferons (IFNs), tumor necrosis factor alpha (TNF-alpha), and interleukin (IL) production and virus replication, uninfected and vesicular stomatitis virus (VSV)-infected human peripheral blood leukocytes (PBLs) were used. Four pulverized preparations obtained from roots of Scutellaria and a Sigma-Aldrich preparation of purified baicalein were used in the study. RPMI extracts containing different amounts of baicalein and wogonin were used to study the effect on VSV replication in PBLs. PBLs express ex vivo individually differentiated cytokine-dependent resistance/innate immunity to viral infections. The degree of resistance was estimated on the basis of VSV replication in PBLs. The results obtained indicate that baicalein- and wogonin-containing extracts modulate cytokine production, that is inhibit IFN-alpha and IFN-gamma and stimulate TNF-alpha and IL (IL-12, IL-10) production. They also augment the resistance of PBLs to VSV. Extract from S. baicalensis containing baicalein and wogonin regulates the innate antiviral immunity by modulation of cytokine production and stimulation of human leukocyte resistance.
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PMID:Production of cytokines and stimulation of resistance to viral infection in human leukocytes by Scutellaria baicalensis flavones. 1877 41

A vaccine for the prevention of human immunodeficiency virus (HIV) infection is desperately needed to control the AIDS pandemic. To address this problem, we developed vesicular stomatitis virus glycoprotein-pseudotyped replication-defective simian immunodeficiency viruses (dSIVs) as an AIDS vaccine strategy. The dSIVs retain characteristics of a live attenuated virus without the drawbacks of potential virulence caused by replicating virus. To improve vaccine immunogenicity, we incorporated CD40 ligand (CD40L) into the dSIV envelope. CD40L is one of the most potent stimuli for dendritic cell (DC) maturation and activation. Binding of CD40L to its receptor upregulates expression of major histocompatibility complex class I, class II, and costimulatory molecules on DCs and increases production of proinflammatory cytokines and chemokines, especially interleukin 12 (IL-12). This cytokine polarizes CD4(+) T cells to Th1-type immune responses. DC activation and mixed lymphocyte reaction (MLR) studies were performed to evaluate the immunogenicity of CD40L-dSIV in vitro. Expression levels of CD80, CD86, HLA-DR, and CD54 on DCs transduced with the dSIV incorporating CD40L (CD40L-dSIV) were significantly higher than on those transduced with dSIV. Moreover, CD40L-dSIV-transduced DCs expressed up to 10-fold more IL-12 than dSIV-transduced DCs. CD40L-dSIV-transduced DCs enhanced proliferation and gamma interferon secretion by naive T cells in an MLR. In addition, CD40L-dSIV-immunized mice exhibited stronger humoral and cell-mediated immune responses than dSIV-vaccinated animals. The results show that incorporating CD40L into the dSIV envelope significantly enhances immunogenicity. As a result, CD40L-dSIVs can be strong candidates for development of a safe and highly immunogenic AIDS vaccine.
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PMID:Incorporation of CD40 ligand into the envelope of pseudotyped single-cycle Simian immunodeficiency viruses enhances immunogenicity. 1903 23

Signal-transducing adaptor molecules (STAMs) are involved in growth factor and cytokine signaling as well as receptor degradation, and they form complexes with a number of endocytic proteins, including Hrs and Eps15. In this study, we demonstrate that STAM proteins also localize prominently to early exocytic compartments and profoundly regulate Golgi morphology. Upon STAM overexpression in cells, the Golgi apparatus becomes extensively fragmented and dispersed, but when STAMs are depleted, the Golgi becomes highly condensed. Under both scenarios, vesicular stomatitis virus G protein-green fluorescent protein trafficking to the plasma membrane is markedly inhibited, and recovery of Golgi morphology after Brefeldin A treatment is substantially impaired in STAM-depleted cells. Furthermore, STAM proteins interact with coat protein II (COPII) proteins, probably at endoplasmic reticulum (ER) exit sites, and Sar1 activity is required to maintain the localization of STAMs at discrete sites. Thus, in addition to their roles in signaling and endocytosis, STAMs function prominently in ER-to-Golgi trafficking, most likely through direct interactions with the COPII complex.
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PMID:STAM adaptor proteins interact with COPII complexes and function in ER-to-Golgi trafficking. 1905 91

A vaccine for human immunodeficiency virus (HIV) infection is desperately needed to control the AIDS pandemic. To address this problem, we constructed single-cycle simian immunodeficiency viruses (SIVs) pseudotyped with the glycoprotein of vesicular stomatitis virus and expressing different levels of gamma interferon (IFN-gamma) as a potential vaccine strategy. We previously showed that IFN-gamma expression by pseudotyped SIVs does not alter viral single-cycle infectivity. T cells primed with dendritic cells transduced by pseudotyped SIVs expressing high levels of IFN-gamma had stronger T-cell responses than those primed with dendritic cells transduced by constructs lacking IFN-gamma. In the present study, we tested the immunogenicities of these pseudotyped SIVs in a rat model. The construct expressing low levels of rat IFN-gamma (dSIV(LRgamma)) induced higher levels of cell-mediated and humoral immune responses than the construct lacking IFN-gamma (dSIV(R)). Rats vaccinated with dSIV(LRgamma) also had lower viral loads than those vaccinated with dSIV(R) when inoculated with a recombinant vaccinia virus expressing SIV Gag-Pol as a surrogate challenge. The construct expressing high levels of IFN-gamma (dSIV(HRgamma)) did not further enhance immunity and was less protective than dSIV(LRgamma). In conclusion, the data indicated that IFN-gamma functioned as an adjuvant to augment antigen-specific immune responses in a dose- and cell type-related manner in vivo. Thus, fine-tuning of the cytokine expression appears to be essential in designing vaccine vectors expressing adjuvant genes such as the gene for IFN-gamma. Furthermore, we provide evidence of the utility of the rat model to evaluate the immunogenicities of single-cycle HIV/SIV recombinant vaccines before initiating studies with nonhuman primate models.
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PMID:Lower levels of gamma interferon expressed by a pseudotyped single-cycle simian immunodeficiency virus enhance immunogenicity in rats. 1907 26

Interferon gamma (IFN-gamma) is a pleiotropic cytokine that is recognized as an important modulator of the immune response. To date, there is no report that prokaryocyte-derived recombinant equine IFN-gamma has antiviral activity. In this report, the gene coding equine IFN-gamma (EIFN-gamma) mature protein was cloned into pET-28a (+) and the recombinant EIFN-gamma was expressed in Escherichia coli (E. coli). The antiviral activity of expressed recombinant EIFN-gamma was evaluated by using a recombinant Vesicular Stomatitis Virus expressing green fluorescence protein (rVSV-GFP) system in the equine fetal kidney-78 cell line (EFK-78). The GFP expression in the EFK-78 cells dramatically decreased in the cells treated with EIFN-gamma in a dose-dependent manner, comparing with the mock-treated cells. The titer of antiviral activity was 1 x 10(3)AU/ml. These results demonstrated that the EIFN-gamma expressed in this study had good biological activity. Pure forms and sufficient quantities of biologically active IFN-gamma could facilitate the study of its activities in modulating immune responses both in vivo and in vitro.
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PMID:Expression of biologically active recombinant equine interferon-gamma in Escherichia coli. 1927 27

To study the role of IL-12 as a third signal for T-cell activation and differentiation in vivo, direct IL-12 signaling to CD8(+) T cells was analyzed in bacterial and viral infections using the P14 T-cell adoptive transfer model with CD8(+) T cells that lack the IL-12 receptor. Results indicate that CD8(+) T cells deficient in IL-12 signaling were impaired in clonal expansion after Listeria monocytogenes infection but not after infection with lymphocytic choriomeningitis virus, vaccinia virus or vesicular stomatitis virus. Although limited in clonal expansion after Listeria infection, CD8(+) T cells deficient in IL-12 signaling exhibited normal degranulation activity, cytolytic functions, and secretion of IFN-gamma and TNF-alpha. However, CD8(+) T cells lacking IL-12 signaling failed to up-regulate KLRG1 and to down-regulate CD127 in the context of Listeria but not viral infections. Thus, direct IL-12 signaling to CD8(+) T cells determines the cell fate decision between short-lived effector cells and memory precursor effector cells, which is dependent on pathogen-induced local cytokine milieu.
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PMID:Effector T-cell differentiation during viral and bacterial infections: Role of direct IL-12 signals for cell fate decision of CD8(+) T cells. 1954 44

The gene sequence encoding mature porcine interferon-gamma (PoIFN-gamma) fused with a C-terminal 6x histidine tag was cloned into the baculovirus pFastBac Dual vector of the Bac-to-Bac Baculovirus expression system under the control of PH promoter. The authentic signal sequence of porcine interferon-gamma was substituted with the honeybee melittin (HBM) signal sequence, and expressed in insect cells. The recombinant proteins were detected by SDS-PAGE and immunofluorescence assay. The nickel affinity column purified recombinant porcine interferon-gamma with HBM signal peptide (rPoIFN-gammaH) was shown to be a 19kDa protein as confirmed by Western blot analysis. The recombinant PoIFN-gammaH was shown to have cytokine activity, inhibiting the cytopathic effect of vesicular stomatitis virus (VSV) in PK-15 cells at about 1.07x10(6)U/mL. The 2(-7) dilution of the rPoIFN-gammaH in culture supernatant protected the MARC-145 cells from the cytopathic effect caused by 100TCID(50) of porcine reproductive and respiratory syndrome virus.
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PMID:Secretory expression of porcine interferon-gamma in baculovirus using HBM signal peptide and its inhibition activity on the replication of porcine reproductive and respiratory syndrome virus. 1955 14

Vaccines currently licensed for the prevention of seasonal influenza induce antibodies against the influenza hemagglutinin (HA) and neuraminidase (NA) contained in the vaccine preparation but require at least 2 weeks after immunization for the development of protective immunity. These vaccines do not induce protective responses quickly enough to blunt the effects of infection when administered after exposure. We have developed a novel vaccine based on recombinant vesicular stomatitis virus which expresses the influenza hemagglutinin (rVSV HA) and protects mice from lethal influenza challenge when the vaccine is administered intramuscularly at least 24h after delivery of the influenza challenge virus. To our knowledge this is the first vaccine that effectively protects animals from lethal influenza challenge when delivered by a systemic route after influenza exposure has occurred. The induction of HA-specific immune responses by the vaccine is necessary for full protection from challenge, because animals immunized with an empty rVSV vector were not protected equally. Our results are consistent with a model in which vaccination induces an immediate antiviral cytokine response, followed by development of humoral and cellular immune responses which act to reduce pulmonary viral loads and accelerate recovery. Consistent with this model, mice vaccinated with the specific vaccine rVSV HA had high levels of IFN-alpha in the serum by 24h after challenge/vaccination, developed serum neutralizing Ab to influenza 2 days prior to control animals, and had detectable anti-HA CD8 T cells present in the peripheral blood 3 days prior to control mice.
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PMID:Intramuscular immunization with a vesicular stomatitis virus recombinant expressing the influenza hemagglutinin provides post-exposure protection against lethal influenza challenge. 1981 11


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