No abstract

Objective. Nuclear factor-B (NF-B) has been implicated as a therapeutic target for the treatment of rheumatoid arthritis (RA). The purpose of this study was to determine whether A20, a universal inhibitor of NF-B, might have antiarthritic effects.Methods. An adenovirus containing A20 complementary DNA (AdA20) was used to deliver A20 to human rheumatoid fibroblast-like synoviocytes (FLS) in vitro as well as to mice with collagen-induced arthritis (CIA) in vivo via intraarticular injection into the ankle joints bilaterally.Results. In vitro experiments demonstrated that AdA20 suppressed NF-B activation, chemokine production, and matrix metalloproteinase secretion induced by tumor necrosis factor ␣ in FLS. Mice with CIA that were treated with AdA20 had a lower cumulative disease incidence and severity of arthritis, based on hind paw thickness, radiologic and histopathologic findings, and inflammatory cytokine levels, than did control virus-injected mice. The protective effects of AdA20 were mediated by the inhibition of the NF-B signaling pathway. The severity of arthritis was also significantly decreased in the untreated front paws, indicating a beneficial systemic effect of local suppression of NF-B. Surprisingly, mice treated with AdA20 after the onset of CIA had significantly decreased arthritis severity from the onset of clinical signs to the end of the study.Conclusion. These results suggest that using A20 to block the NF-B pathway in rheumatoid joints reduces both the inflammatory response and the tissue destruction. The development of an immunoregulatory strategy based on A20 may therefore have therapeutic potential in the treatment of RA.

The antibiotic resistance rates of H. pylori in Jinju had a different pattern to other regions. The antibiotic resistance rates of H. pylori showed geographic variation, and local data should be provided as a guideline for treating H. pylori infection.

Helicobacter pylori causes gastroduodenal disease, which is mediated in part by its outer membrane proteins (OMPs). To identify OMPs of H. pylori strain 26695, we performed a proteomic analysis. A sarcosine-insoluble outer membrane fraction was resolved by two-dimensional electrophoresis with immobilized pH gradient strips. Most of the protein spots, with molecular masses of 10 to 100 kDa, were visible on the gel in the alkaline pI regions (6.0 to 10.0). The proteome of the OMPs was analyzed by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. Of the 80 protein spots processed, 62 spots were identified; they represented 35 genes, including 16 kinds of OMP. Moreover, we identified 9 immunoreactive proteins by immunoblot analysis. This study contributes to the characterization of the H. pylori strain 26695 proteome and may help to further elucidate the biological function of H. pylori OMPs and the pathogenesis of H. pylori infection.Helicobacter pylori is a spiral-shaped, microaerophilic gramnegative bacterium that causes acute and chronic gastritis, gastroduodenal ulcers, and gastric cancer (3,7,21,40). More than half of the world's population has suffered from H. pylori infection (4, 5, 46). Surface proteins, including flagella, urease, and adhesin, are known to be involved in the pathogen-host relationship between H. pylori and the human gastric mucosa. A correlation between the motility state of some H. pylori isolates, and their ability to colonize the gastric epithelium has been established in experiments with gnotobiotic piglets (18). Urease enables H. pylori to survive in the acidic environment of the stomach (13) and plays a key role in colonizing the gastric mucosa (17). Adhesins, including BabA (25), AlpA/AlpB (42), HopZ (43), and SabA (26), are known to adhere to gastric epithelial cells.The genomes of two H. pylori strains have been sequenced (2, 49) and extensively compared (1). Of 64 theoretically predicted outer membrane proteins (OMPs), at least 8, including adhesins and porins, have been confirmed experimentally. However, it is unclear whether all of the predicted OMPs are expressed.Several methodological approaches have been applied to the identification of H. pylori surface proteins, including OMPs. Sarbarth et al. (48) selectively biotinylated intact H. pylori with the hydrophilic reagent sulfosuccinimidyl-6-(biotinamido)-hexanoate and purified the labeled proteins by membrane isolation, solubilization, and affinity chromatography. Exner et al. (19) purified OMP fractions by sucrose gradient centrifugation and identified heat-mobile OMPs, which may be porins, by using two-dimensional (2-DE) gel electrophoresis. Doig et al. (15) identified six OMPs in a sarcosine-insoluble OMP fraction and by using monoclonal antibodies, demonstrated that these proteins are located within or are associated with the outer membrane. In addition, by comparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of outer membrane fractions isolated by different isol...

These results indicated that quantitative analysis of proteome components is a feasible method for examining disease-associated proteins and clustering clinical strains of H. pylori.