| 1. |
- Bankvall, Maria, et al.
(author)
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The engagement of oral-associated lymphoid tissues during oral versus gastric antigen administration
- 2016
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In: Immunology. - : Wiley. - 0019-2805. ; 149:1, s. 98-110
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Journal article (peer-reviewed)abstract
- The role of oral-associated lymphoid tissues during induction of oral tolerance still remains elusive. Therefore, the aim was to compare T-cell activation and induction of tolerance to ovalbumin (OVA) presented through either of two routes; deposited into the oral cavity, or the stomach, thereby bypassing the oral cavity. OVA was administered by the oral or gastric route to BALB/c mice that had received OVA-specific DO11.10+ CD4(+) T cells, stained with CellTrace Violet dye, through intravenous injection. Proliferating OVA-specific T cells were detected in the nose-associated lymphoid tissues (NALT) and the cervical, mesenteric and peripheral lymph nodes at different time-points following OVA exposure. OVA-specific T-cell proliferation was initially observed in the NALT 1hr after oral, but not gastric, administration. However, at day 1, proliferation at this site was also detected after gastric administration and profound proliferation was observed at all sites by day 4. For the oral route the degree of proliferation observed was lower in the peripheral lymph nodes by day 4 compared with the other sites. These results demonstrate a similar activation pattern achieved by the two routes. However, the NALT distinguishes itself as a site of rapid T-cell activation towards fed antigens irrespective of feeding regimen. To evaluate induction of tolerance a semi-effective OVA dose was used, to detect differences in the degree of tolerance achieved. This was performed in a model of OVA-induced airway hypersensitivity. No differences in tolerance induction were observed between the two administration routes.
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| 2. |
- Flach, Carl-Fredrik, 1977, et al.
(author)
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Pro-inflammatory cytokine gene expression in the stomach correlates with vaccine-induced protection against Helicobacter pylori infection in mice: an important role for interleukin-17 during the effector phase. : Immune correlates to H. pylori protection
- 2011
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In: Infection and immunity. - 1098-5522. ; 79:2, s. 879-886
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Journal article (peer-reviewed)abstract
- CD4(+) T cells have been shown to be essential for vaccine-induced protection against Helicobacter pylori infection in mice. Less is known about relative contributions of individual cell subpopulations, such as TH1 and TH17 cells, and their associated cytokines. The aim of the present study was to find immune correlates to vaccine-induced protection and further study their role in protection against H. pylori infection. Immunized and unimmunized mice were challenged with H. pylori and immune responses were compared. Vaccine-induced protection was assessed by measuring H. pylori colonization in the stomach. Gastric gene expression of TH1- and/or TH17-associated cytokines was analyzed by quantitative PCR and contributions of individual cytokines to protection were evaluated by antibody-mediated in vivo neutralization. By analyzing immunized and unimmunized mice a significant inverse correlation could be demonstrated between levels of interleukin (IL)-12p40, tumor necrosis factor α (TNF), interferon γ (IFNγ) and IL-17 gene expression and number of H. pylori in the stomach of individual animals after challenge. In a kinetic study, up-regulation of TNF, IFNγ and IL-17 coincided with vaccine-induced protection 7 days after H. pylori challenge and was sustained for at least 21 days. In vivo neutralization of these cytokines during the effector phase of the immune response revealed a significant role for IL-17, but not for IFNγ or TNF, in vaccine-induced protection. In conclusion, although both TH1- and TH17-associated gene expression in the stomach correlate with vaccine-induced protection against H. pylori infection, our study indicates that mainly TH17 effector mechanisms are of critical importance to protection.
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| 3. |
- Ostberg, Anna Karin, et al.
(author)
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Inflammatory cytokine release is affected by surface morphology and chemistry of titanium implants.
- 2015
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In: Journal of materials science. Materials in medicine. - : Springer Science and Business Media LLC. - 1573-4838 .- 0957-4530. ; 26:4
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Journal article (peer-reviewed)abstract
- To investigate in vitro cellular cytokine expression in relation to commercially pure titanium discs, comparing a native surface to a fluorinated oxide nanotube surface. Control samples pure titanium discs with a homogenous wave of the margins and grooves and an often smeared-out surface structure. Test samples pure titanium discs with a fluorinated titanium oxide chemistry and surface morphology with nanopore/tube geometry characterized by ordered structures of nanotubes with a diameter of ≈120nm, a spacing of ≈30nm, and a wall thickness of ≈10nm. Cross-section view showed vertically aligned nanotubes with similar lengths of ≈700nm. Peripheral blood mononuclear leucocytes were cultured for 1, 3, and 6days according to standard procedures. BioPlex Pro™ assays were used for analysis and detection of cytokines. Selected inflammatory cytokines are reported. A pronounced difference in production of the inflammatogenic cytokines was observed. Leucocytes exposed to control coins produced significantly more TNF-α, IL-1ß, and IL-6 than the test nanotube coins. The effect on the TH2 cytokine IL-4 was less pronounced at day 6 compared to days 1 and 3, and slightly higher expressed on the control coins. The morphology and surface chemistry of the titanium surface have a profound impact on basic cytokine production in vitro. Within the limitations of the present study, it seems that the fluorinated oxide nanotube surface results in a lower inflammatory response compared to a rather flat surface that seems to favour inflammation.
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| 4. |
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| 5. |
- Raghavan, Sukanya, 1974, et al.
(author)
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Sublingual immunization protects against Helicobacter pylori infection and induces T and B cell responses in the stomach. : Sublingual immunization against H. pylori infection
- 2010
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In: Infection and immunity. - 1098-5522. ; 78:10, s. 4251-60
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Journal article (peer-reviewed)abstract
- Sublingual (SL) immunization has been described as an effective novel way to induce mucosal immune responses in the respiratory and genital tracts. We examined the potential of SL immunization against Helicobacter pylori to stimulate immune responses in the gastrointestinal mucosa and protect against H. pylori infection. Mice received two SL immunizations with H. pylori lysate antigens and cholera toxin as an adjuvant, and after challenge with live H. pylori bacteria, their immune responses and protection were evaluated, as were immune responses prior to challenge. SL immunization induced enhanced proliferative responses to H. pylori antigens in cervicomandibular lymph nodes and provided at least the same level of immune responses and protection as corresponding intragastric immunization. Protection in SL-immunized mice was associated with strong H. pylori-specific serum IgG and IgA antibody responses in the stomach and intestine, with strong proliferation and gamma interferon (IFN-γ) and interleukin-17 (IL-17) production by spleen and mesenteric lymph node T cells stimulated with H. pylori antigens in vitro, and with increased IFN-γ and IL-17 gene expression in the stomach compared to levels in infected unimmunized mice. Immunohistochemical studies showed enhanced infiltration of CD4(+) T cells and CD19(+) B cells into the H. pylori-infected stomach mucosa of SL-immunized but not unimmunized H. pylori-infected mice, which coincided with increased expression of the mucosal addressin cell adhesion molecule (MAdCAM-1) and T and B cell-attracting chemokines CXCL10 and CCL28. We conclude that, in mice, SL immunization can effectively induce protection against H. pylori infection in association with strong T and B cell infiltration into the stomach.
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| 7. |
- Wihlborg, Anna-Karin, et al.
(author)
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ADP Receptor P2Y12 Is Expressed in Vascular Smooth Muscle Cells and Stimulates Contraction in Human Blood Vessels.
- 2004
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In: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636. ; 24:10, s. 1810-1815
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Journal article (peer-reviewed)abstract
- Objective - ADP plays an important role in platelet aggregation by activating P2Y(12) receptors. We assessed the hypothesis that P2Y(12) receptors are expressed in vascular smooth muscle cells (VSMC). Methods and Results - P2Y(12) receptor mRNA was found to have a high expression among the P2 receptors in human VSMC, significantly higher than the other 2 ADP receptors (P2Y(1) and P2Y(13), real-time polymerase chain reaction). Western blots gave a band of 50 kD, similar to that in platelets. To unmask a P2Y(12) receptor-mediated vasoconstriction by simulating the in vivo situation, vessels were precontracted to a submaximal level. 2-MeSADP stimulated contractions in vessel segments from internal mammary artery (IM), IM branches and small veins (E-max = 15 +/- 6% of 60 mmol/L K+ contraction, pEC(50) = 5.6 +/- 0.6, E-max = 21 +/- 1%, pEC(50) = 6.8 +/- 0.1, and E-max = 48 +/- 9%, pEC(50) = 6.6 +/- 0.4). The selective P2Y(12) antagonist AR-C67085 blocked 2-MeSADP contractions. The contraction was not reduced in patients using clopidogrel, a drug inhibiting ADP-induced platelet aggregation by blocking the P2Y(12) receptor. This may be explained by the high instability of the active clopidogrel metabolite that never reaches the systemic circulation. Conclusion - ADP acting on P2Y(12) receptors not only is important for platelet activation but also stimulates vasoconstriction. Stable drugs with antagonistic effects on P2Y(12) receptors, affecting both platelets and VSMC, could be of double therapeutic benefit in their prevention of both thrombosis and vasospasm.
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