ABSTRACT
@#Cyclophilin A (CypA) is the first foldable enzyme in human cells that has peptidyl proliferase-trans isomerase activity and has a strong proinflammatory effect. CD147 can act as the signal receptor of CypA. The interaction of the two through cell-surface heparin binding activates extracellular regulated protein kinases (ERK1/2) and nuclear factor kappa-B (NF-κB) signaling pathways in macrophages and increases the expression of MMPs and other inflammatory factors. The CypA/CD147 interaction regulates inflammation, promotes the inflammatory response and bone resorption and is involved in the pathological processes of a variety of systemic diseases. CypA and CD147 may take part in the chemotaxis of inflammatory cells, increase white blood cell infiltration in tissues, and increase CypA and CD147 expression in periodontitis gum tissue and gingival groove liquid with inflammation, prompting their interaction to promote the progression of periodontitis. However, the specific function of the signaling pathways in the periodontitis mechanism still requires further elucidation.
ABSTRACT
For improving epitope immunogenicity and achieving the co-immunization, late protein 1 (L1) of HPV type 16 (HPV16L1) was selected as the vector to carry the dominant epitope of Toxoplasma gondii because of the shared common population between Toxoplasma gondii and human papillomavirus (HPV). RSepitope-HPV16L1 (RSepitope fused at the "N-terminus" of HPV16L1) and HPV16L1-RSepitope (RSepitope fused at the "C-terminus" of HPV16L1) chimeras were constructed. After transfection of COS-7 cells with the recombinants, Western blot, RT-PCR, and immunofluorescence experiments confirmed that RSepitope-HPV16L1 could successfully express the corresponding mRNA and protein of RSepitope and HPV16L1, but the HPV16L1-RSepitope construct could not. A "prime-boost" immunization program was applied in mice to further evaluate the immune response elicited by the constructs, and the RSepitope-HPV16L1 immunization group produced the most significantly increased humoral and cellular immune responses (the highest RSepitope-specific IgG antibody level and the highest IFN-γ production, respectively), in which both elevated Th1 and Th2 immune responses were obtained. Moreover, the advantage of HPV16L1 as an epitope carrier was remarkable for RSepitope-HPV16L1, which induced a more prominent immunological response than RSepitope alone (without fusion with HPV16L1). Our research indicated that the N-terminus of HPV16L1 could be a better insertion site for enhancing target epitope immunogenicity, and our study offers a design for epitope vaccine of reasonable combination.
Subject(s)
Animals , Mice , Antibody Formation , Epitopes , Immunization , Mice, Inbred BALB C , Toxoplasma , Vaccination , Vaccines, DNAABSTRACT
@#BACKGROUND: High mobility group box 1 protein (HMGB1) is a highly conserved, ubiquitous protein in the nuclei and cytoplasm of nearly all cell types. HMGB1 is secreted into the extracellular milieu and acts as a proinflammatory cytokine. In this article we reviewed briefly the cellular immune response mediated by HMGB1 in inflammation and sepsis. METHODS: This systemic review is mainly based on our own work and other related reports. RESULTS: HMGB1 can actively affect the immune functions of many types of cells including T lymphocytes, regulatory T cells (Tregs), dendritic cells (DCs), macrophages, and natural killer cells (NK cells). Various cellular responses can be mediated by HMGB1 which binds to cell-surface receptors [e.g., the receptor for advanced glycation end products (RAGE), Toll-like receptor (TLR)2, and TLR4]. Anti-HMGB1 treatment, such as anti-HMGB1 polyclonal or monoclonal antibodies, inhibitors (e.g., ethyl pyruvate) and antagonists (e.g., A box), can protect against sepsis lethality and give a wider window for the treatment opportunity. CONCLUSION: HMGB1 is an attractive target for the development of new therapeutic strategies in the treatment of patients with septic complications.
ABSTRACT
A large number of negative air ions have been detected in forests, at spas, and near waterfalls. The air ion had been reported to improve the feelings of comfort, feelings of fatigue and occupational efficiency. Almost all the studies were reported by the short-term exposure of the air ions (2-5 hours) on human. We analyzed the physiological effects and laboratory findings of the long-term exposure of negative air ion (ca. 5000/cc, 5 hours/day, 3 weeks) in double-blind methods.<br>For this study, we made the negative air ion producing machines, in which the steam was combined with electric discharge by high-voltage electrodes. The machines could constantly produce high amount of negative ions (ca. 5, 000 counts/cc). We set these machines in the rest rooms of ten volunteer and programmed to spout negative air ions when they were sleeping at midnight (AM1:00-6:00) for 3 weeks. After 3 weeks exposure of negative air ions or sham condition, we checked the physical and mental tests and sampled the blood.<br>In the exposure of negative air ions, some of the depressive scales and subjective feelings (scores from Arthritis Impact Measurement Scales (AIMS2)) were better than in those in the sham condition, and the local perspiration of palm, which reflected sympathetic nerve function, also decreased by mental and physical stress in the exposure ions more than in the sham condition. This showed that the negative air ion decreased the stress of the sympathetic nerve function. In laboratory findings, there were no significant differences between the clinical data with ions and without ions, and it was shown that ion was harmless in the range of 5, 000 counts/cc 5 hours/day. The percentage of natural killer (NK) cells with the exposure of the ions was lower than without ions. This also indicated the air ion decreased the stress of human.<br>It was shown that the negative air ion might improve human activities and remove the stress. The mechanism of the negative air ions for human is not clear, so that further studies will be needed.