Ginger extract inhibits LPS induced macrophage activation and function

<p>Abstract</p> <p>Background</p> <p>Macrophages play a dual role in host defence. They act as the first line of defence by mounting an inflammatory response to antigen exposure and also act as antigen presenting cells and initiate the adaptive immune response. They are also the primary infiltrating cells at the site of inflammation. Inhibition of macrophage activation is one of the possible approaches towards modulating inflammation. Both conventional and alternative approaches are being studied in this regard. Ginger, an herbal product with broad anti inflammatory actions, is used as an alternative medicine in a number of inflammatory conditions like rheumatic disorders. In the present study we examined the effect of ginger extract on macrophage activation in the presence of LPS stimulation.</p> <p>Methods</p> <p>Murine peritoneal macrophages were stimulated by LPS in presence or absence of ginger extract and production of proinflammatory cytokines and chemokines were observed. We also studied the effect of ginger extract on the LPS induced expression of MHC II, B7.1, B7.2 and CD40 molecules. We also studied the antigen presenting function of ginger extract treated macrophages by primary mixed lymphocyte reaction.</p> <p>Results</p> <p>We observed that ginger extract inhibited IL-12, TNF-α, IL-1β (pro inflammatory cytokines) and RANTES, MCP-1 (pro inflammatory chemokines) production in LPS stimulated macrophages. Ginger extract also down regulated the expression of B7.1, B7.2 and MHC class II molecules. In addition ginger extract negatively affected the antigen presenting function of macrophages and we observed a significant reduction in T cell proliferation in response to allostimulation, when ginger extract treated macrophages were used as APCs. A significant decrease in IFN-γ and IL-2 production by T cells in response to allostimulation was also observed.</p> <p>Conclusion</p> <p>In conclusion ginger extract inhibits macrophage activation and APC function and indirectly inhibits T cell activation.</p

High tibial osteotomy in Sweden, 1998–2007: A population-based study of the use and rate of revision to knee arthroplasty

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Most studies on high tibial osteotomies (HTOs) have been hospital-based and have included a limited number of patients. We evaluated the use and outcome-expressed as rate of revision to knee arthroplasty-of HTO performed in Sweden with 9 million inhabitants, 1998-2007. 3, 161 HTO procedures on patients 30 years or older (69% men) who were operated on for knee osteoarthritis in Sweden, 1998-2007, were identified through the inpatient and outpatient care registers of the Swedish National Board of Health and Welfare. Pertinent data were verified through surgical records. Conversions of HTO to knee arthroplasty before 2010 were identified through the Swedish Knee Arthroplasty Register (SKAR). The 10-year survival was determined using revision to an arthroplasty as the endpoint. The number of HTOs decreased by one third between 1998 and 2007, from 388 operations a year to 257 a year. Most of the HTOs were performed with open wedge osteotomy using external fixation. The cumulative revision rate at 10 years was 30% (95% CI: 28-32). The risk of revision increased with increasing age and was higher in women than in men (RR = 1.3, CI: 1.1-1.5). If being without an artificial joint implant is considered to be beneficial, then HTO is an excellent alternative to knee arthroplasty in younger and/or physically active patients suffering from knee osteoarthritis.Swedish Research Council Swedish Rheumatism Association King Gustaf V 80-year Birthday Fund Faculty of Medicine, Lund University Region Skan

Phenotypic and functional analysis of lymphocytes infiltrating osteolytic tumors: use as a possible therapeutic approach of osteosarcoma

BACKGROUND: Osteosarcoma is the most common type of primary bone tumor. The use of aggressive chemotherapy has drastically improved the prognosis of the patients with non-metastatic osteosarcomas, however the prognosis of the patients with metastasis is still very poor. Then, new and more effective treatments for curing osteosarcoma, such as immunotherapy are needed. Tumor-infiltrating lymphocytes (TIL) have been involved in the control of tumor development and already assessed with success for the treatment of several cancers including melanoma. While TIL represent a fascinating therapeutic approach in numerous malignant pathologies, there is few report concerning adult bone-associated tumors including osteosarcoma. METHODS: Human TIL were isolated and characterized (phenotype, lytic activity) from twenty-seven patients with bone-associated tumors (osteosarcoma, Ewing's sarcoma, giant cell tumor, chondrosarcoma, plasmocytoma and bone metastases). Similar experiments were performed using rat osteosarcoma model. RESULTS: While TIL with a main CD4(+ )profile were easily isolated from most of the tumor samples, only TIL extracted from osteosarcoma were cytotoxic against allogeneic tumor cells. In all cases, TIL lytic activity was significantly higher compared to autologous peripheral blood leukocytes. Similar data were observed in rat osteosarcoma model where TIL were characterized by a main CD4(+ )profile and high lytic activity against allogeneic and autologous tumor cells. Moreover, rat TIL expansion was not accompanied by refractoriness to further activation stimulus mainly by tumor antigens. CONCLUSION: These results demonstrated that TIL therapy could be a very efficient strategy for the treatment of adult osteosarcoma

Association of microsomal epoxide hydrolase polymorphisms and lung cancer risk

lung cancer ris

Beta-Amyloid Peptides Enhance the Proliferative Response of Activated CD4+CD28+ Lymphocytes from Alzheimer Disease Patients and from Healthy Elderly

Alzheimer's disease (AD) is the most frequent form of dementia among elderly. Despite the vast amount of literature on non-specific immune mechanisms in AD there is still little information about the potential antigen-specific immune response in this pathology. It is known that early stages of AD include β-amyloid (Aβ)- reactive antibodies production and inflammatory response. Despite some evidence gathered proving cellular immune response background in AD pathology, the specific reactions of CD4+ and CD8+ cells remain unknown as the previous investigations yielded conflicting results. Here we investigated the CD4+CD28+ population of human peripheral blood T cells and showed that soluble β-amyloids alone were unable to stimulate these cells to proliferate significantly, resulting only in minor, probably antigen-specific, proliferative response. On the other hand, the exposure of in vitro pre-stimulated lymphocytes to soluble Aβ peptides significantly enhanced the proliferative response of these cells which had also lead to increased levels of TNF, IL-10 and IL-6. We also proved that Aβ peptide-enhanced proliferative response of CD4+CD28+ cells is autonomous and independent from disease status while being associated with the initial, ex vivo activation status of the CD4+ cells. In conclusion, we suggest that the effect of Aβ peptides on the immune system of AD patients does not depend on the specific reactivity to Aβ epitope(s), but is rather a consequence of an unspecific modulation of the cell cycle dynamics and cytokine production by T cells, occurring simultaneously in a huge proportion of Aβ peptide-exposed T lymphocytes and affecting the immune system performance

Expression of cytoplasmic and nuclear Survivin in primary and secondary human glioblastoma

Clinically, human glioblastoma (GBM) may develop de novo or from a low-grade glioma (secondary GBM), and molecular alterations in the two pathways may differ. This study examined the status of Survivin expression and apoptosis in 30 primary and 26 secondary GBMs. Our results show that cytoplasmic Survivin positivity was significantly (P<0.001) more frequent in primary GBMs (83%) than that in secondary GBMs (46%). In addition, an inverse correlation of cytoplasmc Survivin positivity with GBM apoptotic index, and a positive association between cytoplasmic Survivin and size of the tumours were observed. These results suggest that cytoplasmic Survivin, via its antiapoptotic function, may be involved in the tumorigenesis of many primary GBMs, but only in a small fraction of secondary GBMs. Furthermore, the overall progression times from low-grade precursor lesions to secondary GBMs were significantly shorter (P<0.05) in cytoplasmic Survivin-positive cases (mean, 15.6 months) than those in Survivin-negative cases (mean, 23.8 moths), and the positive expression level of Survivin in cytoplasm was upregulated in most secondary GBMs when compared to matched pre-existing low-graded lesions. These results suggest that the increased accumulation of Survivin in the cytoplasm of more malignant glioma cells may prove to be a selective advantage, thus accelerating progression to a more aggressive phenotype

Heat shock proteins in chronic kidney disease

Heat shock proteins (HSP) form a heterogenous, evolutionarily conserved group of molecules with high sequence homology. They mainly act as intracellular chaperones, protecting the protein structure and folding under stress conditions. The extracellular HSP, released in the course of damage or necrosis, play a pivotal role in the innate and adaptive immune responses. They also take part in many pathological processes. The aim of this review is to update the recent developments in the field of HSP in chronic kidney disease (CKD), in regard to three different aspects. The first is the assessment of the role of HSP, either positive or deleterious, in the pathogenesis of CKD and the possibilities to influence its progression. The second is the impact of dialysis, being a potentially modifiable stressor, on HSP and the attempt to assess the value of these proteins as the biocompatibility markers. The last area is that of kidney transplantation and the potential role of HSP in the induction of the immune tolerance in kidney recipients