Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adjuvant arthritis in Lewis rats is induced by the subcutaneous injection of Mycobacterium tuberculosis in mineral oil, and the predominant T cell immune reactivity is against the heat shock protein 65 derived peptide 176-190. We treated Lewis rats with human recombinant G-CSF followed by (i.v) administration of peptide 176-190 after induction of adjuvant arthritis (AA), and observed decreased disease severity, joint destruction, new bone formation and joint ankylosis. Treatment with G-CSF alone was also effective, but to a lesser extent. In addition, we found that splenocytes from rats treated with G-CSF had reduced antigen presenting capacity compared with splenocytes from vehicle treated rats. Primed lymph node cells from G-CSF plus peptide treated rats showed a marked reduction in proliferation and secretion of IFN-gamma after stimulation with the heat shock protein peptide in vitro as compared to controls.
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PMID:Treatment of adjuvant arthritis with granulocyte-colony stimulating factor and peptide derived from heat shock protein 65. 1274 77

Adjuvant arthritis (AA) is induced by immunizing Lewis rats with Mycobacterium tuberculosis suspended in adjuvant. The mycobacterial 65-kDa heat shock protein (HSP65) contains at least one epitope associated with the pathogenesis of AA: T cell clones that recognize an epitope formed by aa 180-188 of HSP65 react with self-cartilage and can adoptively transfer AA. Nevertheless, vaccination with HSP65 or some of its T cell epitopes can prevent AA by a mechanism that seems to involve cross-reactivity with the self-60-kDa HSP60. We recently demonstrated that DNA vaccination with the human hsp60 gene can inhibit AA. In the present work, we searched for regulatory epitopes using DNA vaccination with HSP60 gene fragments. We now report that specific HSP60 DNA fragments can serve as effective vaccines. Using overlapping HSP60 peptides, we identified a regulatory peptide (Hu3) that was specifically recognized by the T cells of DNA-vaccinated rats. Vaccination with Hu3, or transfer of splenocytes from Hu3-vaccinated rats, inhibited the development of AA. Vaccination with the mycobacterial homologue of Hu3 had no effect. Effective DNA or peptide vaccination was associated with enhanced T cell proliferation to a variety of disease-associated Ags, along with a Th2/3-like shift (down-regulation of IFN-gamma secretion and enhanced secretion of IL-10 and/or tumor growth factor beta1) in response to peptide Mt176-190 (the 180-188 epitope of HSP65). The regulatory response to HSP60 or its Hu3 epitope included both Th1 (IFN-gamma) and Th2/3 (IL-10/tumor growth factor beta1) secretors. These results show that regulatory mechanisms can be activated by immunization with relevant self-HSP60 epitopes.
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PMID:DNA fragments of the human 60-kDa heat shock protein (HSP60) vaccinate against adjuvant arthritis: identification of a regulatory HSP60 peptide. 1450 Jun 49

T-cell responses to heat shock proteins (Hsp) have been suggested to play a role not only in inflammatory conditions, but also in various human autoimmune diseases and in the allograft response. Previous data from our group suggested that during the early posttransplantation (post-Tx) period (<6 months post-Tx), the anti-Hsp60 T-cell repertoires in renal transplant recipients were predominantly proinflammatory. In the later period, they were predominantly regulatory. In agreement with our results, diversification of the T-cell responses toward the carboxy-terminal determinants of Hsp60, related to the resolution of the inflammatory process, was shown in an experimental model of adjuvant arthritis. It has not been clarified whether this diversification is also present in transplantation. In this context, our objective was to analyze cytokine production against autologous Hsp60 peptides from different regions of the protein, using peripheral blood mononuclear cells of 9 renal transplant recipients at 2 timepoints after transplantation: early (<6 months) and late (>1 year). IFN gamma production induced by Hsp60 peptides was observed in 71% and 75% of the patients in the early and late post-Tx periods, respectively. Interleukin (IL)-10 production induced by Hsp60 peptides was observed in 28% of the patients in the early period and in 62% in the late period. Interestingly, the production of IL-10 was induced mainly by peptides of the intermediate and the C-terminal regions. This suggests a predominance of autoreactive regulatory anti-Hsp T-cell repertoire in the late post-Tx period, which predominantly recognize peptides from the intermediate and C-terminal regions of the protein.
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PMID:T-cell response to self HSP60 peptides in renal transplant recipients: a regulatory role? 1519 86

Extracellular heat shock protein 60 (HSP60) has been considered a proinflammatory danger signal. Yet, HSP60 can also down-regulate experimental immune arthritis and diabetes models by specific inhibition of Th1-like responses. We now report that HSP60 in vitro differentially modulates the expression of Th1/Th2 transcription factors in human T cells: HSP60 down-regulates T-bet, NF-kappaB, and NFATp and up-regulates GATA-3, leading to decreased secretion of TNF-alpha and IFN-gamma and enhanced secretion of IL-10. These effects depended on TLR2 signaling and could not be attributed to LPS or to other contaminants. In BALB/c mice, HSP60 in vivo inhibited the clinical, histological, and serological manifestations of Con A-induced hepatitis associated with up-regulated T cell expression of suppressor of cytokine signaling 3 and GATA-3 and down-regulated T-bet expression. These results provide a molecular explanation for the effects of HSP60 treatment on T cell inflammation via innate regulation of the inflammatory response.
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PMID:Heat shock protein 60 inhibits Th1-mediated hepatitis model via innate regulation of Th1/Th2 transcription factors and cytokines. 1574 53

T cells have an important role during the development of autoimmune diseases. In adjuvant arthritis, a model for rheumatoid arthritis, we found that the percentage of CD4+ T cells expressing the activation marker CD134 (OX40 antigen) was elevated before disease onset. Moreover, these CD134+ T cells showed a specific proliferative response to the disease-associated epitope of mycobacterial heat shock protein 60, indicating that this subset contains auto-aggressive T cells. We studied the usefulness of CD134 as a molecular target for immune intervention in arthritis by using liposomes coated with a CD134-directed monoclonal antibody as a drug targeting system. Injection of anti-CD134 liposomes subcutaneously in the hind paws of pre-arthritic rats resulted in targeting of the majority of CD4+CD134+ T cells in the popliteal lymph nodes. Furthermore, we showed that anti-CD134 liposomes bound to activated T cells were not internalized. However, drug delivery by these liposomes could be established by loading anti-CD134 liposomes with the dipalmitate-derivatized cytostatic agent 5'-fluorodeoxyuridine. These liposomes specifically inhibited the proliferation of activated CD134+ T cells in vitro, and treatment with anti-CD134 liposomes containing 5'-fluorodeoxyuridine resulted in the amelioration of adjuvant arthritis. Thus, CD134 can be used as a marker for auto-aggressive CD4+ T cells early in arthritis, and specific liposomal targeting of drugs to these cells via CD134 can be employed to downregulate disease development.
Arthritis Res Ther 2005
PMID:CD134 as target for specific drug delivery to auto-aggressive CD4+ T cells in adjuvant arthritis. 1589 47

The presence of anti-heat shock protein 60 (Hsp60) antibodies in healthy individuals and the association of these antibodies with diseases such as arthritis and atherosclerosis are well documented. However, there is limited population-level data on interindividual variation in anti-Hsp60 levels. We investigated the influence of early-life factors on IgG reactivity to human Hsp60 at age 18 years. A population-based prospective birth cohort study included 5914 births in the city of Pelotas, Brazil, in 1982. Early-life exposures were documented during home visits in childhood. In 2000, 79% of all males in the cohort were traced. Sera from a systematic 20% sample (411 subjects) were analyzed. Anti-Hsp60 total IgG reactivity was determined by ELISA. Data were analyzed using analysis of variance and generalized linear models. Anti-Hsp60 reactivity was lognormally distributed and showed a significant direct correlation with low birthweight (p=0.039) and total duration of breastfeeding (p=0.018), of which only the latter remained significant after adjustment for potential confounders. Reactivity was not associated with asthma, pneumonia, diarrhea, or early-life malnutrition. Mother-child immunological interactions, rather than infection/disease factors seem to be associated with reactivity to Hsp60 later in life. This is in agreement with the hypothesis that maternal antibodies influence future antibody profile.
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PMID:Mother-child immunological interactions in early life affect long-term humoral autoreactivity to heat shock protein 60 at age 18 years. 1752 83

Using Western blotting, we investigated IgG antibodies against Mycobacterium bovis heat shock protein 65 (MB-Hsp65) fragments produced by cleavage with cyanogen bromide (CNBr) in 10 healthy controls, 11 patients with juvenile idiopathic arthritis (JIA), and 10 children with various diseases before haematopoietic stem cell transplantation (HSCT). CNBr cleaved MB-Hsp65 to three larger fragments: P1-163, P191-285, and P290-534. Sera of JIA patients and those before HSCT reacted with individual MB-Hsp65 fragments P1-163 and P290-534 significantly more frequently when compared with healthy controls. These results suggested that the key B-cell epitopes of MB-Hsp65 might be located on the aforementioned sequences.
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PMID:Humoral response against Mycobacterium bovis Hsp65 derived fragments in children and young people with various disorders. 1856 76

Largely due to better control of infectious diseases and significant advances in biomedical research, life expectancy worldwide has increased dramatically in the last three decades. However, as the average age of the population has risen, the incidence of chronic age-related diseases such as arthritis, Alzheimer's, Parkinson's, cardiovascular disease, cancer, osteoporosis, benign prostatic hyperplasia, and late-onset diabetes have increased and have become serious public health problem, as well. The etiology of these disorders is still incompletely understood, therefore, neither preventive strategies nor long-term effective treatment modalities are available for these disorders. In keeping with the aforementioned, the ultimate goal in cardiovascular research is to prevent the onset of cardiovascular episodes and thereby allow successful ageing without morbidity and cognitive decline. Herein, I argue that cardiovascular episodes could be contained with relatively simple approaches. Cardiovascular disorder is characterized by cellular and molecular changes that are commonplace in age-related diseases in other organ system, such alterations include increased level of oxidative stress, perturbed energy metabolism, and "horror autotoxicus" largely brought about by the perturbation of ubiquitin -proteasome system, and excessive oxidative stress damage to the cardiac muscle cells and tissues, and cross-reactions of specific antibodies against human heat shock protein 60 with that of mycobacterial heat shock protein 65. "Horror autotoxicus", a Latin expression, is a term coined by Paul Ehrlich at the turn of the last century to describe autoimmunity to self, or the attack of "self" by immune system, which ultimately results to autoimmune condition. Based on the currently available data, the risk of cardiovascular episodes and several other age-related disorders, including cancer, Alzheimer's disease and diabetes, is known to be influenced by the nature and level of food intake. Now, a wealth of scientific data from studies of rodents and monkeys has documented the significant beneficial effects of calorie restriction (CR) or dietary restriction (DR), and multiple antioxidant agents in extending life span and reducing the incidence of progeroid-related diseases. Reduced levels of cellular oxidative stress, protection of genome from deleterious damage, detoxification of toxic molecules, and enhancement of energy homeostasis, contribute to the beneficial effects of dietary restriction and multiple antioxidant agents. Recent findings suggest that employment of DR and multiple antioxidant agents (including, catalase, glutathione peroxidase, CuZn superoxide dismutase, and Mn superoxide dismutase = enzymes forming the primary defense against oxygen toxicity), and ozone therapy may mount an effective resistance to pathogenic factors relevant to the pathogenesis of cardiovascular episodes. Hence, while further studies will be needed to establish the extent to which CR and multiple antioxidant agents will reduce incidence of cardiovascular episodes in humans, it would seem prudent to recommend CR and multiple antioxidant agents as widely applicable preventive approach for cardiovascular disorders and other progeroid-related disorders.
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PMID:Cardiovascular disease could be contained based on currently available data! 1864 94

Heat-shock proteins are molecules with extensive data showing their potential as immunomodulators of different types of diseases. The gene of HSP65 from Mycobacterium leprae has shown prophylactic and immunotherapeutic effects against a broad arrays of experimental models including tuberculosis, leishmaniasis, arthritis and diabetes. With this in mind, we tested the DNAhsp65 vaccine using an experimental model of Paraccocidiodomycosis, an important endemic mycosis in Latin America. The intramuscular immunization with DNAhsp65 induced, in BALB/c mice, an increase of Th1-levels cytokines and a reduction of fungal burdens resulted in a marked reduction of collagen and lung remodeling. DNAhsp65 may be an attractive candidate for prevention, therapy and as an adjuvant for mycosis treatment.
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PMID:DNAhsp65 vaccination induces protection in mice against Paracoccidioides brasiliensis infection. 1902 37

Chlamydia trachomatis (CT) infection is one of the most common causes of reproductive tract diseases and infertility. CT-Hsp60 is synthesized during infection and is released in the bloodstream. As a consequence, immune cells will produce anti-CT-Hsp60 antibodies. Hsp60, a ubiquitous and evolutionarily conserved chaperonin, is normally sequestered inside the cell, particularly into mitochondria. However, upon cell stress, as well as during carcinogenesis, the chaperonin becomes exposed on the cell surface (sf-Hsp60) and/or is secreted from cells into the extracellular space and circulation. Reports in the literature on circulating Hsp and anti-Hsp antibodies are in many cases short on details about Hsp60 concentrations, and about the specificity spectra of the antibodies, their titers, and their true, direct, pathogenetic effects. Thus, more studies are still needed to obtain a definitive picture on these matters. Nevertheless, the information already available indicates that the concurrence of persistent CT infection and appearance of sf-Hsp60 can promote an autoimmune aggression towards stressed cells and the development of diseases such as autoimmune arthritis, multiple sclerosis, atherosclerosis, vasculitis, diabetes, and thyroiditis, among others. At the same time, immunocomplexes composed of anti-CT-Hsp60 antibodies and circulating Hsp60 (both CT and human) may form deposits in several anatomical locations, e.g., at the glomerular basal membrane. The opposite side of the coin is that pre-tumor and tumor cells with sf-Hsp60 can be destroyed with participation of the anti-Hsp60 antibody, thus stopping cancer progression before it is even noticed by the patient or physician.
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PMID:Chlamydia trachomatis infection and anti-Hsp60 immunity: the two sides of the coin. 1971 22


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