Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In previous studies we have induced TSH binding-inhibiting Igs and thyroiditis in BALB/c mice and thyroiditis alone in NOD mice immunized with the extracellular domain of the human TSH receptor produced as a maltose-binding protein fusion in bacteria (MBP-ECD). In this study, our aim was to determine whether thyroiditis can be transferred to syngeneic naive recipients with in vivo and in vitro primed spleen cells. Groups of 6-week-old female BALB/c and NOD mice were immunized ip with MBP-ECD in an adjuvant of alum plus attenuated Bordetella pertussis toxin, on days 0 (100 micrograms), 14, 28, and 35 (50 micrograms). These mice (in vivo primed) and nontreated age- and sex-matched controls were killed on day 43, and their spleens and thyroids were removed, the latter to verify the induction of thyroiditis in the antigen-treated mice. Splenocytes were disrupted mechanically and cultured at 3 x 10(6)/ml in RPMI supplemented with 20 micrograms/ml MBP-ECD for 48-64 h. After this in vitro priming, some of the splenocytes received no further treatment, but a portion was fractionated into a CD4+-enriched population. Groups of 6-week-old female BALB/c and NOD mice were immunized into the tail vein with 100-200 microliters PBS containing approximately 10(5)-10(7) unfractionated T cells (both in vivo primed and not) and CD4+-enriched (in vivo primed) splenocyte populations. The animals were killed 16 days later, and their thyroids were examined histologically and by immunohistochemistry. In addition, levels of antibody to the MBP-ECD priming antigen were assessed by enzyme-linked immunosorbent assay in the antigen- and spleen-treated mice. In the donor animals, in vivo priming resulted in an extensive lymphocytic infiltration of the thyroids in both BALB/c and NOD mice and follicular destruction in the latter. There was no evidence of thyroiditis in all 9 BALB/c mice and all 4 NOD mice who received unfractionated T cells from mice that had not been primed in vivo. In contrast, transfer of MBP-ECD in vivo primed unfractionated T cells resulted in thyroiditis in 9 of 13 BALB/c mice and 5 of 6 NOD mice; similarly, the equivalent CD4+-enriched population produced extensive thyroiditis in 2 of 3 BALB/c mice and all three NOD mice. The most striking difference between the antigen- and spleen-treated mice was in the quantity of the infiltrate, which was much greater in the latter and extended throughout the thyroid glands of these animals. In common with mice treated directly with the MBP-ECD antigen, the infiltrates of both BALB/c and NOD recipient mice contained large numbers of activated T cells expressing the receptor for interleukin-2, and macrophages and dendritic cells were plentiful, particularly in the BALB/c mice, in which B cells and interleukin-10-positive T cells were also present. The most abundant infiltrates, containing numerous CD8+ T cells and follicular destruction, were observed in NOD mice receiving primed unfractionated T cells or CD4+-enriched T cells. In contrast to the donors, none of the recipient animals had circulating antibodies to the MBP-ECD antigen. In conclusion, we have shown that it is possible to transfer thyroiditis with spleen cells from mice primed in vivo with a human TSH receptor preparation. Furthermore, the thyroiditogenic activity appears to reside in the CD4+ population.
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PMID:Transfer of thyroiditis, with syngeneic spleen cells sensitized with the human thyrotropin receptor, to naive BALB/c and NOD mice. 889 27

Our previous results show that recombinant gp41 (aa565-647), the extracellular domain of HIV-1 transmembrane glycoprotein, stimulates interleukin-10 (IL-10) production in human monocytes. The signal cascade transducing this effect is not yet clear. In this study, we examined whether gp41-induced IL-10 up-regulation is mediated by the previously described synergistic activation of cAMP and NF-kappaB pathways. gp41 induced cAMP accumulation in monocytes in a time- and concentration-dependent manner and the adenylate cyclase inhibitor SQ 22536 suppressed gp41-induced IL-10 production in monocytes. In contrast, gp41 failed to stimulate NF-kappaB binding activity in as much as no NF-kappaB bound to the main NF-kappaB-binding site 2 of the IL-10 promoter after addition of gp41. We also examined the involvement of other signal transduction pathways. Specific inhibitors of p70(S6)-kinase (rapamycin), and Gi protein (pertussis toxin), prevented induction of IL-10 production by gp41 in monocytes, while inhibitors of the phosphatidylinositol 3-kinase (PI 3-kinase) (wortmannin) and mitogen-activated protein kinase (MAPK) pathway (PD 98059) did not. Thus HIV-1 gp41-induced IL-10 up-regulation in monocytes may not involve NF-kappaB, MAPK, or PI 3-kinase activation, but rather may operate through activation of adenylate cyclase and pertussis-toxin-sensitive Gi/Go protein to effect p70(S6)-kinase activation.
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PMID:Involvement of adenylate cyclase and p70(S6)-kinase activation in IL-10 up-regulation in human monocytes by gp41 envelope protein of human immunodeficiency virus type 1. 1008 66

Bordetella pertussis is the causative agent of whooping cough, a potentially lethal respiratory disease in children. In immunocompetent individuals, B. pertussis infection elicits an effective adaptive immune response driven by activated CD4(+) T cells. However, live B. pertussis persists in the host for 3 to 4 weeks prior to clearance. Thus, B. pertussis appears to have evolved short-term mechanisms for immune system evasion. We investigated the effects of B. pertussis wild-type strain BP338 on antigen presentation in primary human monocytes. BP338 infection reduced cell surface expression of HLA-DR and CD86 but not that of major histocompatibility complex class I proteins. This change in cell surface HLA-DR expression reflected intracellular redistribution of HLA-DR. The proportion of peptide-loaded molecules was unchanged in infected cells, suggesting that intracellular retention occurred after peptide loading. Although B. pertussis infection of monocytes induced rapid and robust expression of interleukin-10 (IL-10), HLA-DR redistribution did not appear to be explained by increased IL-10 levels. BP338-infected monocytes exhibited reduced synthesis of HLA-DR dimers. Interestingly, those HLA-DR proteins that were generated appeared to be longer-lived than HLA-DR in uninfected monocytes. BP338 infection also prevented gamma interferon (IFN-gamma) induction of HLA-DR protein synthesis. Using mutant strains of B. pertussis, we found that reduction in HLA-DR surface expression was due in part to the presence of pertussis toxin whereas the inhibition of IFN-gamma induction of HLA-DR could not be linked to any of the virulence factors tested. These data demonstrate that B. pertussis utilizes several mechanisms to modulate HLA-DR expression.
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PMID:Bordetella pertussis infection of primary human monocytes alters HLA-DR expression. 1497 50

Bordetella pertussis, the causative agent of whooping cough, is internalized by several cell types, including epithelial cells, monocytes, and neutrophils. Although its ability to survive intracellularly is still debated, it has been proven that cell-mediated immunity (CMI) plays a pivotal role in protection. In this study we aimed to clarify the interaction of B. pertussis with human monocyte-derived dendritic cells (MDDC), evaluating the ability of the bacterium to enter MDDC, to survive intracellularly, to interfere with the maturation process and functional activities, and to influence the host immune responses. The results obtained showed that B. pertussis had a low capability to be internalized by-and to survive in-MDDC. Upon contact with the bacteria, immature MDDC were induced to undergo phenotypic maturation and acquired antigen-presenting-cell functions. Despite the high levels of interleukin-10 (IL-10) and the barely detectable levels of IL-12 induced by B. pertussis, the bacterium induced maturation of MDDC and T helper 1 (Th1) polarized effector cells. Gene expression analysis of the IL-12 cytokine family clearly demonstrated that B. pertussis induced high levels of the p40 and p19 subunits of IL-23 yet failed to induce the expression of the p35 subunit of IL-12. Overall our findings show that B. pertussis, even if it survives only briefly in MDDC, promotes the synthesis of IL-23, a newly discovered Th1 polarizing cytokine. A Th1-oriented immune response is thus allowed, relevant in the induction of an adequate CMI response, and typical of protection induced by natural infection or vaccination with whole-cell vaccines.
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PMID:Bordetella pertussis-infected human monocyte-derived dendritic cells undergo maturation and induce Th1 polarization and interleukin-23 expression. 1573 Oct 58

The prevalence of asthma and allergic disease has increased in many countries, and there has been speculation that immunization promotes allergic sensitization. Bordetella pertussis infection exacerbates allergic asthmatic responses. We investigated whether acellular pertussis vaccine (Pa) enhanced or prevented B. pertussis-induced exacerbation of allergic asthma. Groups of mice were immunized with Pa, infected with B. pertussis, and/or sensitized to ovalbumin. Immunological, pathological, and physiological changes were measured to assess the impact of immunization on immune deviation and airway function. We demonstrate that immunization did not enhance ovalbumin-specific serum immunoglobulin E production. Histopathological examination revealed that immunization reduced the severity of airway pathology associated with sensitization in the context of infection and decreased bronchial hyperreactivity upon methacholine exposure of infected and sensitized mice. These data demonstrate unequivocally the benefit of Pa immunization to health and justify selection of Pa in mass vaccination protocols. In the absence of infection, the Pa used in this study enhanced the interleukin-10 (IL-10) and IL-13 responses and influenced airway hyperresponsiveness to sensitizing antigen; however, these data do not suggest that Pa contributes to childhood asthma overall. On the contrary, wild-type virulent B. pertussis is still circulating in most countries, and our data suggest that the major influence of Pa is to protect against the powerful exacerbation of asthma-like pathology induced by B. pertussis.
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PMID:Acellular pertussis vaccine protects against exacerbation of allergic asthma due to Bordetella pertussis in a murine model. 1575 54

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that leads to an inflammatory demyelination, axonal damage, and progressive neurologic disability that affects approximately 2.5 million people worldwide. The aim of the present research was to test the therapeutic effect of Aloe vera in experimental model of MS. All experiments were conducted on C57BL/6 male mice aged 6-8 weeks. To induce the experimental autoimmune encephalomyelitis (EAE), 250 microg of the myelin oligodendrocyte glycoprotein 35-55 peptide emulsified in complete freund's adjuvant was injected subcutaneously on day 0 over two flank areas. In addition, 200 ng of pertussis toxin in 100 microL phosphate buffered saline was injected intraperitoneally on days 0 and 2. The therapeutic protocol was carried out intragastrically using 120 mg/kg/day Aloe vera from 7 days before to 21 days after EAE induction. The mice were killed 21 days after EAE induction. The brains of mice were removed for histological analysis and their isolated splenocytes were cultured. The results indicated that treatment with Aloe vera caused a significant reduction in severity of the disease in experimental model of MS. Histological analysis showed 3 +/- 2 plaques in Aloe vera-treated mice compared with 5 +/- 1 plaques in control group. The density of mononuclear infiltration in the CNS of Aloe vera-treated mice (500 +/- 200) was significantly less in comparison to 700 +/- 185 cells in control group. Moreover, the serum level of nitric oxide in treatment group was significantly less than control animals. The level of interferon-gamma in cell culture supernatant of treated mice splenocytes was lower than control group, whereas decrease in serum level of interleukin-10 in treatment group was not significant in comparison with control mice. These data indicate that Aloe vera therapy can attenuate the disease progression in experimental model of MS.
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PMID:Therapeutic approach by Aloe vera in experimental model of multiple sclerosis. 2023 7

Immunization with acellular pertussis vaccine (aP) induces higher specific antibody levels and fewer adverse reactions than does immunization with the whole-cell vaccine (wP). However, antibody levels in infants induced by both types of pertussis vaccines wane already after 1 year. Therefore, long-term T-cell responses upon vaccination might play a role in protection against pertussis. In a cross-sectional study (ISRCTN65428640), we investigated T-helper (Th) cell immune responses in wP- or aP-vaccinated children before and after an aP low-dose or high-dose preschool booster at 4 years of age in The Netherlands. T cells were stimulated with pertussis vaccine antigens. The numbers of gamma interferon-producing cells and Th1, Th2, Th17, and interleukin-10 (IL-10) cytokine concentrations were determined. In addition, pertussis-specific IgE levels were measured in plasma. Children being vaccinated with aP vaccinations at 2, 3, 4, and 11 months of age still showed higher pertussis-specific T-cell responses at 4 years of age than did wP-vaccinated children. These T-cell responses failed to show a typical increase in cytokine production after a fifth aP vaccination but remained high after a low-dose booster and seemed to decline even after a high-dose booster. Importantly, elevated IgE levels were induced after this booster vaccination. In contrast, wP-vaccinated children had only low prebooster T-cell responses, and these children showed a clear postbooster T-cell memory response even after a low-dose booster vaccine. Four high-dose aP vaccinations in infancy induce high T-cell responses still present even 3 years after vaccination and enhanced IgE responses after preschool booster vaccination. Therefore, studies of changes in vaccine dosage, timing of pertussis (booster) vaccinations, and the possible association with local side effects are necessary.
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PMID:T-cell responses before and after the fifth consecutive acellular pertussis vaccination in 4-year-old Dutch children. 2301 49

Multiple sclerosis (MS) is an autoimmune disease for which conventional treatments have limited efficacy or side effects. Free radicals are primarily involved in blood-brain barrier disruption and induce neuronal and axonal damage, thus promoting the development of MS. Amifostine, a radioprotective drug used as a cytoprotective agent, attenuates oxidative stress and improves radiation damage by acting as a direct scavenger of reactive oxygen and nitrogen species. The aim of this study was to evaluate the effects of amifostine on MS in a mouse model of experimental autoimmune encephalomyelitis (EAE), which was developed by immunizing C57BL/6 mice with myelin oligodendrocyte glycoprotein and pertussis toxin. EAE mice received intraperitoneal injections of amifostine prior to onset of clinical symptoms and were monitored up to day 15 post induction. We observed abnormal clinical behavioral scores and a decrease in body weight. Histological analysis showed severe inflammatory infiltration and demyelination in the brain and spinal cord lumbar enlargements where significant upregulation of the mRNA expression of the pro-inflammatory cytokines interleukin-6 and interleukin-8, downregulation of the anti-inflammatory cytokine interleukin-10, and obvious microgliosis were also observed. Amifostine treatment potently reversed these abnormal changes. The anti-inflammatory effect of amifostine was associated with the inhibition of reactive oxygen species generation. Furthermore, the expression of proteins involved in the NLRP3 signaling pathway and pyroptosis was decreased. In conclusion, our study showed that amifostine ameliorates induction of experimental autoimmune encephalomyelitis via anti-inflammatory and anti-pyroptosis effects, providing further insights into the use of amifostine for the treatment of MS.
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PMID:Amifostine ameliorates induction of experimental autoimmune encephalomyelitis: Effect on reactive oxygen species/NLRP3 pathway. 3318 64