Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the effects of treatment with recombinant human (rh)IL-6 on clinical, histological and immunological parameters of protracted relapsing (PR) experimental allergic encephalomyelitis (EAE) in DA rats. rhIL-6 (50 microg/rat subcutaneously/day) was given under three different regimens, as early prophylaxis, from 1 day prior to 14 days after immunization, in late prophylaxis, from day +7 until day 21 post-immunization (p.i.) and therapeutically to rats with clinical signs of EAE from day 14 to day 28 p.i. Although rhIL-6 failed to modulate the course of PR-EAE when administered as the early prophylactic regimen, it exerted clear-cut favourable effects on the course of the disease if was administered either as later prophylactic or as therapeutic treatment. Under these conditions, rhIL-6 accelerated recovery from EAE attacks and reduced/milded subsequent EAE episodes as compared to either PBS- or heat-inactivated rhIL-6-treated control rats. In agreement with this clinical effect, relative to PBS-treated rats, the animals injected with rhIL-6 exhibited lower numbers of MHC class II(+) and CD4(+) cells in their spinal cords. rhIL-6-treatment also profoundly modulated the endogenous cytokine network, the treated rats displaying increased numbers of spleen cells expressing mRNA transcripts of the anti-inflammatory cytokines IL-10 and TGF-beta along with simultaneously reduced numbers of mRNAs for TNF-alpha. In addition, upon ex vivo exposure to either myelin basic protein peptide 63-88 (MBP63-88) or to phytoaemagglutinin A, the numbers of IFN-gamma secreting splenocytes was also significantly reduced (ELISPOT analysis) in rhIL-6-treated rats as compared to PBS-treated controls.
 ...
PMID:Curative effects of recombinant human Interleukin-6 in DA rats with protracted relapsing experimental allergic encephalomyelitis. 1143 71

We have characterized the humoral and cellular immune responses of BALB/c mice immunized with HIV-1 Nef regulatory protein encapsulated in poly(DL-lactide-co-glycolide) PLG particles. Three groups of mice were immunized with Nef PLG, Nef in the presence of complete Freund's adjuvant (CFA) or Nef alone in PBS. When titers were compared 7 months after the last injection, anti-Nef titers in mice immunized with Nef PLG were still close to the maximum, whereas a significant decrease was observed in mice immunized with Nef alone (five times lower) or with Nef in CFA (three times lower). These results indicate that Nef PLG is at least a similar or better vector/adjuvant than Nef in CFA concerning the duration of the humoral immune response. The analysis of cytokine profiles (IL-5 and IL-10) and the isotypic patterns of anti-Nef antibodies (predominantly IgG1), in the three groups of mice, indicated a predominant Th2 immune response. Using synthetic peptides covering the entire sequence of Nef, we identified at least three linear epitopes within sequences 32-64, 118-167 and 185-205 in the sera of mice immunized with Nef PLG or Nef CFA. In contrast, anti-Nef antibodies against Nef alone failed to recognize synthetic peptides, indicating that the majority of anti-Nef antibodies were primarily directed against conformational epitopes. We then examined the ability of Nef PLG to prime for the antigen-specific proliferative responses in vitro. The data obtained indicate the presence of both B-cell and T-cell epitopes in the C-terminal fragment of the protein after immunization of mice with Nef encapsulated in PLG particles.
 ...
PMID:Characterization of humoral and cellular immune responses in mice induced by immunization with HIV-1 Nef regulatory protein encapsulated in poly(DL-lactide-co-glycolide) microparticles. 1179 29

The transfer of genes encoding immunomodulatory proteins to the intestinal mucosa is a promising new approach to the treatment of Crohn's disease (CD). This study investigates the therapeutic efficacy of an adenoviral vector encoding IL-10 (AdvmuIL-10) in experimental colitis. BALB/c mice were treated with a single intravenous injection of AdvmuIL-10, empty cassette virus (Adv0) or PBS prior to the induction of trinitrobenzene sulphonic acid (TNBS) colitis. AdvmuIL-10 treatment prevented the severe loss of body weight associated with TNBS administration. In addition, AdvmuIL-10 therapy led to a significant reduction in both stool markers of inflammation (IL-1beta and TNFR-II) and acute phase response (serum amyloid protein). Finally, the histological scores of mice with TNBS colitis treated with AdvmuIL-10 were significantly lower than Adv0- or PBS-treated controls. The therapeutic efficacy of AdvmuIL-10 was associated with a decrease in the IFN-gamma and IL-6 levels detected in colonic homogenates from mice with TNBS colitis, whereas no effect was observed on cytokine release from stimulated systemic lymphocytes. Thus, AdvmuIL-10 is an effective therapy in the TNBS model of colitis. Gene therapy strategies using adenoviral vectors encoding IL-10 may prove to be a potent therapy for chronic inflammatory conditions such as CD.
 ...
PMID:IL-10 gene therapy prevents TNBS-induced colitis. 1245 86

Distinct subsets of dendritic cells (DCs) based on the origin, phenotypes, and the nature of the signals that promote DC maturation can determine polarized immune responses of T cells. In this study, DCs were cultured from mouse bone marrow (BM) progenitors in granulocyte-macrophage colony-stimulating factor (GM-CSF). To generate mature DCs (mDCs), lipopolysaccharide (LPS) was used in the culture for 24 h. LPS-stimulated DCs were phenotypically mature, which exhibited strongly upregulated CD40, B7.1, and B7.2 compared to non-LPS-stimulated immature DCs (imDCs). Both mDCs and imDCs expressed high levels of MHC class II but low level of CD54. mDCs produced higher levels of IL-10 and lower IL-12 compared to imDCs. No IFN-gamma or IL-4 was found in both groups. When mDCs were injected intraperitoneally (i.p.) to the mice with experimental autoimmune encephalomyelitis (EAE), the severity of clinical signs and inflammation in the CNS was significantly suppressed compared to imDC-injected mice (p<0.01) and PBS-injected mice (p<0.02). Moreover, lymphocytes from mDC-injected mice produced lower level of IL-12, IFN-gamma, but higher level of IL-10, compared to imDC-injected and non-DC-injected mice. We conclude that BM-mDCs, but not BM-imDCs, promote Th2 differentiation and have the potential for suppression of inflammatory demyelination.
 ...
PMID:Mature bone marrow-derived dendritic cells polarize Th2 response and suppress experimental autoimmune encephalomyelitis. 1247 84

Oral tolerance is a specific immune unresponsiveness to food antigens to prevent hypersensitivity reactions. We investigated whether zinc deficiency affects oral tolerance. Rats were fed a control (C) or zinc-deficient (ZD) diet, or pair-fed (PF) to ZD rats for 28 d. Beginning on d 7, rats were administered ovalbumin (OVA) orally to induce tolerance, or PBS 3 times/wk, and were then immunized by OVA injection. The proliferation of mesenteric lymph node (MLN) and spleen lymphocytes after in vitro OVA stimulation and the delayed-type hypersensitivity were higher in OVA-fed ZD than in OVA-fed C rats and not different between OVA- and PBS-fed ZD rats, indicating a suppression of tolerance. Lymphocyte proliferation did not differ between PF and C rats. Expressions of cytokines involved in oral tolerance, i.e., interleukin (IL)-4, IL-10 and transforming growth factor-beta, were higher in OVA- than in PBS-fed C rats, but not in ZD rats. Apoptosis was higher in OVA- than in PBS-fed C rats but not different between OVA- and PBS-fed ZD rats. Inflammation and ulcerations that were not present in ZD rats on d 7 (ZD(7)) developed in OVA- or PBS-fed ZD rats. Compared with ZD(7) rats, tumor necrosis factor-alpha and cytokine-induced neutrophil chemoattractant were higher in OVA- and PBS-fed ZD rats, whereas interferon-gamma increased only in OVA-fed ZD rats. In conclusion, zinc deficiency suppresses oral tolerance through dysregulation of cytokine expression and lack of antigen-specific clonal deletion. We suggest that abrogation of tolerance may lead to development of mucosal inflammation and damage.
 ...
PMID:Zinc deficiency suppresses the development of oral tolerance in rats. 1251 89

OBJECTIVE: To investigate the effects of IL-18 gene-modified fetal hepatocytes (AdmIL-18/MNL.CL2) intrasplenic transplantation on mouse immune function. METHODS: Forty mice were evenly divided into 4 groups of 10. Each group received an intrasplenic transplantation one of the following: AdmIL-18/BNL.CL2, Ad-LacZ/BNL.CL2 (virus control), BNL.CL2 (cell control) and PBS (blank control). After two weeks, the mice were sacrificed. Serum cytokine levels, Mpsi and splenic cell culture supernatant and liver tissue extracts supernatants were measured using ELISA. Hepatic cytokines mRNA expression were determined by RT-PCR. THe cytotoxicity of peritoneal Mpsi and NK activity of spienocytes were detected by LDH release assay. The proliferation of splenic lymphocytes was determined by MTT assay. RESULTS: The IL-18, IL-2,IFN-gamma, TNF-alpha levels of serum, Mpsi and splenocyte culture supernatant, liver tissue extracts supernatants in mice transplanted with AdmIL-18/BNL.CL2 were higher and the IL-4, IL-10 levels were lower compared to their levels in other 3 groups. The highest IL-18, IL-2, IFN-gamma, TNF-alpha and the lowest IL-4, IL-10 mRNA expressions in the liver were observed in mice transplanted with AdmIL-18/BNL.CL2. The mice transplanted with AdmIL-18/BNL.Cl2 showed significantly increases cytotoxicity of Mpsi, NK activity and splenic cell proliferation compared with the other 3 groups. CONCLUSION: AdmIL-18 can be effectively transfected into mice fetal heptocytes which subsequently IL-18. Intransplenic transplantation of IL-18 gene-modified fetal hepatocytes may augment mouse immune function and provide an useful basis for targeted gene therapy of liver disease.
 ...
PMID:[Effects of intrasplenic transplantation of IL-18 gene-modified fetal hepatocytes on mouse immune function] 1253 73

The role of macrophages in Pseudomonas aeruginosa corneal infection in susceptible (cornea perforates), C57BL/6 (B6) vs resistant (cornea heals), BALB/c mice was tested by depleting macrophages using subconjunctival injections of clodronate-containing liposomes before corneal infection. Both groups of inbred mice treated with clodronate-liposomes compared with PBS-liposomes (controls) exhibited more severe disease. In B6 mice, the cornea perforated and the eye became extremely shrunken, whereas in BALB/c mice, the cornea perforated rather than healed. The myeloperoxidase assay detected significantly more PMN in the cornea of both groups of mice treated with clodronate-liposomes vs PBS-liposomes. In independent experiments, ELISA analysis showed that protein levels for IL-1 beta, macrophage-inflammatory protein 2, and macrophage-inflammatory protein 1 alpha, all regulators of PMN chemotaxis, also were elevated in both groups of mice treated with clodronate-liposomes. Bacterial plate counts in B6 mice treated with clodronate-liposomes were unchanged at 3 days and were higher in control-treated mice at 5 days postinfection (p.i.), whereas in BALB/c mice, bacterial load was significantly elevated in the cornea of mice treated with clodronate-liposomes at both 3 and 5 days p.i. mRNA expression levels for pro (IFN-gamma and TNF-alpha)- and anti (IL-4 and IL-10)-inflammatory cytokines also were determined in BALB/c mice treated with clodronate-liposomes vs control-treated mice. Expression levels for IFN-gamma were significantly elevated in mice treated with clodronate-liposomes at 3 and 5 days p.i., while IL-10 levels (mRNA and protein) were reduced. These data provide evidence that macrophages control resistance to P. aeruginosa corneal infection through regulation of PMN number, bacterial killing and balancing pro- and anti-inflammatory cytokine levels.
 ...
PMID:Macrophages restrict Pseudomonas aeruginosa growth, regulate polymorphonuclear neutrophil influx, and balance pro- and anti-inflammatory cytokines in BALB/c mice. 1273 70

Invariant NKT (inv. NKT) cells co-express an invariant alpha beta T cell receptor and the NK receptor NK1.1 and, upon CD1d-restricted recognition of the glycosphingolipid antigen alpha-galactosyl ceramide (alphaGalCer), secrete large amounts of regulatory cytokines. We investigated whether alphaGalCer-dependent activation of inv. NKT cells protects from experimental autoimmune encephalomyelitis (EAE), an immune-mediated disease of the central nervous system mimicking multiple sclerosis, induced in C57BL/6 mice by the myelin oligodendrocyte glycoprotein (MOG) encephalitogenic peptide aa 35-55. alphaGalCer was administered at the time of immunization s.c., mixed with complete Freund's adjuvant and MOG35-55 peptide, or administered i.p., diluted in PBS. EAE onset was delayed and disease severity was decreased only when alphaGalCer was s.c. administered. The protective effect of s.c. administration of alphaGalCer was associated with a markedly enhanced IFN-gamma production by liver-confined inv. NKT cells which, in turn, suppressed Th1-cytokine production and fostered secretion of IL-10 from MOG35-55-specific T cells. In vivo neutralization of IFN-gamma, but notIL-4, reversed the protective effect induced by s.c. administration of alphaGalCer, further confirming the critical regulatory role exerted by IFN-gamma-producing inv. NKT cells. Our results indicate that alphaGalCer, properly administered, may elicit an inv. NKT-cell-mediated suppressive effect on the effector function of encephalitogenic T cells; this effect is able to ameliorate autoimmunedemyelination.
 ...
PMID:Activation of invariant NKT cells by alphaGalCer administration protects mice from MOG35-55-induced EAE: critical roles for administration route and IFN-gamma. 1281 43

We have shown previously that in addition to IL-4, IL-5 and IL-10, antigen-specific interferon-gamma (IFN-gamma) production by spleen cells from ovalbumin (OVA)/Alum-immunized mice is inhibited by the administration of royal jelly (RJ). Since it has been shown that both Th1 and Th2 cytokines play pathogenic roles in the generation of atopic dermatitis (AD), we have examined whether RJ suppresses the development of AD-like skin lesions in NC/Nga mice induced by repeated application of picryl chloride (PiCl) under specific pathogen-free (SPF) conditions. Oral administration of RJ to the PiCl-treated NC/Nga mice inhibited the development of AD-like skin lesions in these mice as exemplified by the significant decrease in the total skin severity scores and the decrease in hypertrophy, hyperkeratosis, and infiltration of the epidermis and corium by inflammatory cells. IFN-gamma production by spleen cells from PiCl-treated NC/Nga mice in response to TNP-KLH was partially but significantly inhibited by the oral administration of RJ, while IFN-gamma production by Con A-stimulated spleen cells was not affected. Since inducible nitric oxide (NO) synthase (iNOS)-derived NO has been suggested as an important immunoregulatory mediator in inflammatory autoimmune diseases, we have also examined the expression of iNOS in the dorsal skin lesions of PiCl-treated NC/Nga mice. Interestingly, the expression of iNOS was significantly increased in the skin lesions of RJ-administered mice compared with those of control PBS-administered mice. Thus, our results suggest that RJ suppresses the development of AD-like skin lesions in PiCl-treated NC/Nga mice, possibly by a combination of down-regulating TNP-specific IFN-gamma production and up-regulating iNOS expression.
 ...
PMID:Oral administration of royal jelly inhibits the development of atopic dermatitis-like skin lesions in NC/Nga mice. 1289 Apr 29

We have demonstrated that induction of mucosal tolerance to E-selectin, a cytokine-inducible adhesion molecule restricted to activating blood vessels, prevents ischemic and hemorrhagic stroke in spontaneously hypertensive, genetically stroke-prone (SHR-SP) rats. We now examine whether mucosal tolerance to E-selectin has protective effects in ischemic brain damage after permanent middle cerebral artery occlusion (MCAO) in SHR-SP rats and whether these effects are related to generation of regulatory T cells. Rats were exposed to intranasal administration of E-selectin every other day for 10 days (single tolerization group) or on two tolerization schedules separated by 11 days (booster tolerization group). Control groups received PBS on corresponding schedules. MCAO was performed 48 h after the last dose of E-selectin or PBS. There were 45.8% and 37.9% (P < 0.05) decreases of infarction volume in the E-selectin booster group compared with the PBS group at 6 and 48 h, respectively. Single tolerization with E-selectin had only a slight trend toward a decrease in infarction volume (6.3%). CD8-positive cells were decreased in brains of E-selectin booster animals (46.6%, P < 0.01) compared with controls; splenocyte-culture supernatant levels of IL-10 were increased (59.3%, P < 0.05) in E-selectin booster animals. A decrease of infarction volume (34%, P < 0.05) was also observed in SHR-SP rats subjected to MCAO after adoptive transfer of splenocytes from E-selectin-tolerized compared with PBS-tolerized donors. The results indicate that, in addition to preventing stroke, mucosal tolerance to E-selectin is cytoprotective. Thus, immunomodulation targeted to activated blood vessel segments can both reduce stroke occurrence and attenuate brain damage if a stroke supervenes.
 ...
PMID:Mucosal tolerance to E-selectin provides cell-mediated protection against ischemic brain injury. 1464 8


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>