Interleukin-23 Receptor Gene Polymorphism May Enhance Expression of the IL-23 Receptor, IL-17, TNF-α and IL-6 in Behcet’s Disease

<div><p>Purpose</p><p>Recent studies identified an association between Behcet’s disease (BD) and the IL-23R gene polymorphism (rs17375018) in different populations. This study examined whether this IL-23R gene polymorphism is associated with enhanced inflammatory responses.</p><p>Methods</p><p>We recruited 27 BD patients and 32 controls with three genotypes. Peripheral blood mononuclear cells (PBMCs) were seeded with or without anti-CD3 and CD28. Cells were incubated for 24 hours, and then supernatants were collected and stored at −20◦C until analyzed. Levels of interferon (IFN)-γ, tissue necrosis factor (TNF)-α, interleukin (IL)-17 and IL-6 were detected by ELISA. IL-23R expression was assessed by quantitative real-time polymerase chain reaction (RT-PCR).</p><p>Results</p><p>The expression of IL-23R was significantly higher in both BD patients and healthy controls with the GG genotype compared to the AG and AA genotype with anti-CD3 and CD28 stimulation (all P-value < 0.05). Among the PBMCs cultured with anti-CD3 and CD28 stimulation, there was an elevated secretion of TNF-α, IL-6 and IL-17 in BD patients and healthy controls with the GG genotype. However, there was no significant change in secretion of IFN- γ in BD patients and healthy controls among the genotype of this IL-23R gene polymorphism.</p><p>Conclusions</p><p>The results suggest that the GG genotype of the rs17375018 variant in the IL-23R gene enhances pro-inflammatory cytokine responses.</p></div

The IL-17, IFN-γ, TNF-α and IL-6 expression levels of peripheral blood mononuclear cells (PBMC) obtained from healthy individuals and patients with Behcet’s disease with the rs17375018 AA, AG and GG genotypes.

<p>The IL-17, IFN-γ, TNF-α and IL-6 expression levels of peripheral blood mononuclear cells (PBMC) obtained from healthy individuals and patients with Behcet’s disease with the rs17375018 AA, AG and GG genotypes.</p

Clinical characteristic of study participants.

<p>Clinical characteristic of study participants.</p

Additional file 1: of Housing type and myopia: the mediating role of parental myopia

The National Eye Care Study Questionnaire (Parental Questionnaire for Grade 1–3 Children). (DOC 67 kb

5′-<i>Epi</i>-SPA-6952A, a new insecticidal 24-membered macrolide produced by S<i>treptomyces diastatochromogenes</i> SSPRC-11339

<p>A new 24-membered macrolide, 5′-<i>epi</i>-SPA-6952A (<b>1</b>), was isolated from the cultured broth of <i>Streptomyces diastatochromogenes</i>. The structure was elucidated by means of spectroscopic methods and comparing with literature data of the known 24-membered macrolide SPA-6952A. Compound <b>1</b> was found to show significant insecticidal activity against oriental armyworm(<i>Mythimna separata</i> Walker) with LC₅₀ value of 10.26 mg/L.</p

Association of TLR4 and Treg in <i>Helicobacter pylori</i> Colonization and Inflammation in Mice

<div><p>The host immune response plays an important role in the pathogenesis of <i>Helicobacter pylori</i> infection. The aim of this study was to clarify the immune pathogenic mechanism of <i>Helicobacter pylori</i> infection via TLR signaling and gastric mucosal Treg cells in mice. To discover the underlying mechanism, we selectively blocked the TLR signaling pathway and subpopulations of regulatory T cells in the gastric mucosa of mice, and examined the consequences on <i>H</i>. <i>pylori</i> infection and inflammatory response as measured by MyD88, NF-κB p65, and Foxp3 protein expression levels and the levels of Th1, Th17 and Th2 cytokines in the gastric mucosa. We determined that blocking TLR4 signaling in <i>H</i>. <i>pylori</i> infected mice decreased the numbers of Th1 and Th17 Treg cells compared to controls (P < 0.001–0.05), depressed the immune response as measured by inflammatory grade (P < 0.05), and enhanced <i>H</i>. <i>pylori</i> colonization (P < 0.05). In contrast, blocking CD25 had the opposite effects, wherein the Th1 and Th17 cell numbers were increased (P < 0.001–0.05), immune response was enhanced (P < 0.05), and <i>H</i>. <i>pylori</i> colonization was inhibited (P < 0.05) compared to the non-blocked group. In both blocked groups, the Th2 cytokine IL-4 remained unchanged, although IL-10 in the CD25 blocked group was significantly decreased (P < 0.05). Furthermore, MyD88, NF-κB p65, and Foxp3 in the non-blocked group were significantly lower than those in the TLR4 blocked group (P < 0.05), but significantly higher than those of the CD25 blocked group (P < 0.05). Together, these results suggest that there might be an interaction between TLR signaling and Treg cells that is important for limiting <i>H</i>. <i>pylori</i> colonization and suppressing the inflammatory response of infected mice.</p></div

Western blot detection conditions for MyD88 and Foxp3.

<p>Western blot detection conditions for MyD88 and Foxp3.</p

Grade of gastritis after <i>H</i>. <i>pylori</i> infection.

<p>(A) The grade of gastritis with TLR4 blocked; (B) The grade of gastritis with CD25 blocked; (C) HE staining of the gastric mucosa of the control group; (D) HE staining of the gastric mucosa of the <i>H</i>. <i>pylori</i> infection group; (E) HE staining of the gastric mucosa of the TLR4 blocked control group; (F) HE staining of the gastric mucosa of the TLR4 blocked <i>H</i>. <i>pylori</i> infection group; (G) HE staining of the gastric mucosa of the CD25 blocked control group; (H) HE staining of the gastric mucosa of the CD25 blocked <i>H</i>. <i>pylori</i> infection group. ^a<i>P</i> < 0.001 between <i>H</i>. <i>pylori</i> and control or TLR4 blocked control groups; ^b<i>P</i> < 0.01 between TLR4 blocked <i>H</i>. <i>pylori</i> and control or TLR4 blocked control groups; ^c<i>P</i> < 0.05 between <i>H</i>. <i>pylori</i> and TLR4 blocked <i>H</i>. <i>pylori</i> groups (Fig 2A). ^a<i>P</i> < 0.001 <i>vs</i>. control and CD25 blocked control groups; ^b<i>P</i> < 0.05 between <i>H</i>. <i>pylori</i> and CD25 blocked <i>H</i>. <i>pylori</i> groups (Fig 2B).</p

Expression of Th1, Th17, and Th2 cytokines in the gastric mucosa after <i>H</i>. <i>pylori</i> infection.

<p>(A) The expression of Th1 and Th17 with TLR4 blocked; (B) The expression of Th1 and Th17 with CD25 blocked; (C) The expression of Th2 with TLR4 blocked; (D) The expression of Th2 with CD25 blocked. ^a<i>P</i> < 0.05–0.001 <i>vs</i>. the control or TLR4 blocked control groups; ^b<i>P</i> < 0.001–0.05 between TLR4 blocked <i>H</i>. <i>pylori</i> and <i>H</i>. <i>pylori</i> groups (Fig 3A); ^a<i>P</i> < 0.001 <i>vs</i>. the control and CD25 blocked control groups; ^b<i>P</i> < 0.001–0.05 between CD25 blocked <i>H</i>. <i>pylori</i> and <i>H</i>. <i>pylori</i> groups (Fig 3B). ^a<i>P</i> < 0.01 <i>vs</i>. control and TLR4 blocked control groups (Fig 3C); ^a<i>P</i> < 0.01–0.001 <i>vs</i>. control and CD25 blocked control groups; ^b<i>P</i> < 0.05 between CD25 blocked and non-blocked <i>H</i>. <i>pylori</i> groups (Fig 3D).</p

Expression of MyD88 and Foxp3 in the gastric mucosa after <i>H</i>. <i>pylori</i> infection by western blot.

<p>(A) The expression of MyD88 and Foxp3 with TLR4 blocked; (B) The expression of MyD88 and Foxp3 with CD25 blocked; (C, D) The expression of MyD88 and Foxp3 by western blotting. ^a<i>P</i> < 0.001 <i>vs</i>. control and TLR4 blocked control groups; ^b<i>P</i> < 0.001–0.05 <i>vs</i>. control and TLR4 blocked control groups and the <i>H</i>. <i>pylori</i> group (Fig 5A). ^a<i>P</i> < 0.01–0.001 <i>vs</i>. control and CD25 blocked control groups; ^b<i>P</i> < 0.05 between CD25 blocked <i>H</i>. <i>pylori</i> and <i>H</i>. <i>pylori</i> groups (Fig 5B).</p