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Cytokine Activity (cytokine + activity)
Selected AbstractsCrystal Structure of an EMAP-II-Like Cytokine Released from a Human tRNA SynthetaseHELVETICA CHIMICA ACTA, Issue 4 2003Xiang-Lei Yang Aminoacyl-tRNA synthetases catalyze the first step of protein synthesis by aminoacylation of tRNAs. Remarkably, biological fragments of two human enzymes , tyrosyl-tRNA synthetase (TyrRS) and tryptophanyl-tRNA synthetase , are active cytokines produced by proteolysis or alternative splicing. One is a C-terminal fragment of TyrRS (C-TyrRS) that has potent activity for chemotaxis of leukocytes and monocytes and for stimulating production of other cytokines. Significantly, the cytokine activity of C-TyrRS is absent in the context of the full-length native protein. Unknown is the mechanism by which domain-release from the dimeric native protein activates the cytokine. Here, the crystal structure of C-TyrRS is presented at 2.2,Å resolution. This structure is similar to that of endothelial monocyte-activating protein II (EMAP-II), with critical residues of a heptapeptide element important for chemotaxis activity exposed on the first strand of a , -barrel of the monomeric unit. In contrast, the same residues of C-TyrRS are buried in an operational model for native TyrRS. Importantly, C-TyrRS is shown here to be monomeric when released from dimeric native TyrRS. Further analysis suggests that the critical residues are exposed when tRNA is bound. Thus, tRNA binding to native TyrRS may be an additional or alternative way to activate cytokine signaling. [source] Differential cytokine activity and morphology during wound healing in the neonatal and adult rat skinJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 6 2007W. Wagner Abstract Wound-healing mechanisms change during transition from prenatal to postnatal stage. Cytokines are known to play a key role in this process. The current study investigated the differential cytokine activity and healing morphology during healing of incisional skin wounds in rats of the ages neonatal (p0), 3 days old (p3) and adult, after six different healing times (2 hrs to 30 days). All seven tested cytokines (Transforming Growth Factor (TGF) ,, TGF,1, ,,2 and ,,3, IGF 1, Platelet Derived Growth Factor A (PDGF A), basic Fibroblast Growth Factor (bFGF) exhibited higher expression in the adult wounds than at the ages p0 and p3. Expression typically peaked between 12 hrs and 3 days post-wounding, and was not detectable any more at days 10 and 30. The neonate specimen showed more rapid re-epithelialization, far less inflammation and scarring, and larger restitution of original tissue architecture than their adult counterparts, resembling a prenatal healing pattern. The results may encourage the use of neonatal rat skin as a wound-healing model for further studies, instead of the more complicated prenatal animal models. Secondly, the data may recommend inhibition of PDGF A, basic FGF or TGF-,1 as therapeutic targets in efforts to optimize wound healing in the adult organism. [source] Assessment of periodontal conditions and systemic disease in older subjectsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 9 2002I. Focus on osteoporosis Abstract Background: Osteoporosis (OPOR) is a common chronic disease, especially in older women. Patients are often unaware of the condition until they experience bone fractures. Studies have suggested that OPOR and periodontitis are associated diseases and exaggerated by cytokine activity. Panoramic radiography (PMX) allows studies of mandibular cortical index (MCI), which is potentially diagnostic for OPOR. Aims: i) To study the prevalence of self-reported history of OPOR in an older, ethnically diverse population, ii) to assess the agreement between PMX/MCI findings and self-reported OPOR, and iii) to assess the likelihood of having both a self-reported history of OPOR and a diagnosis of periodontitis. Materials and methods: PMX and medical history were obtained from 1084 subjects aged 60,75 (mean age 67.6, SD ± 4.7). Of the films, 90.3% were useful for analysis. PMXs were studied using MCI. The PMXs were used to grade subjects as not having periodontitis or with one of three grades of periodontitis severity. Results: A positive MCI was found in 38.9% of the subjects, in contrast to 8.2% self-reported OPOR. The intraclass correlation between MCI and self-reported OPOR was 0.20 (P < 0.01). The likelihood of an association between OPOR and MCI was 2.6 (95%CI: 1.6, 4.1, P < 0.001). Subjects with self-reported OPOR and a positive MCI had worse periodontal conditions (P < 0.01). The Mantel-Haentzel odds ratio for OPOR and periodontitis was 1.8 (95%CI: 1.2, 2.5, P < 0.001). Conclusions: The prevalence of positive MCI was high and consistent with epidemiological studies, but only partly consistent with a self-reported history of osteoporosis with a higher prevalence of positive MCI in Chinese women. Horizontal alveolar bone loss is associated with both positive self-reported OPOR and MCI. [source] Rebamipide enema therapy as a treatment for patients with active distal ulcerative colitisJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2007Ryuichi Furuta Background:, The clinical efficacy of corticosteroids in the treatment of ulcerative colitis (UC) is well-established. However, prolonged usage of these drugs can result in serious complications. Rebamipide {2-(4-chlorobenzoylamino)-3[2-(1H)-quinolinon-4-yl] propionic acid}, a cytoprotective agent, has been reported to have anti-inflammatory activity and to repair mucosal injury in animal colitis models. The aim of the present study was to assess the clinical efficacy and safety of a novel Rebamipide enema therapy in UC patients. Methods:, Twenty patients with the active distal type of UC in whom corticosteroid treatment had been unsuccessful were treated with rectal administration of Rebamipide twice a day for 3 weeks, during which corticosteroid dosage was kept constant. The efficacy of treatment was assessed from clinical symptoms and endoscopic findings. The anti-inflammatory effect of Rebamipide was also examined by monitoring changes in the intensity of histological inflammation and levels of cytokine activity in the rectal mucosa. Results:, At 3 weeks after the initiation of Rebamipide enema therapy, 11 patients (55%) achieved clinical remission. Sixteen (80%) were colonoscopically judged to be responders, with decreased levels of interleukin (IL)-1, but not of IL-8, and an increased ratio of IL-1 receptor antagonist/IL-1, in organ cultures of mucosal tissues. The change in the number of infiltrating neutrophils was not significantly correlated with the clinical response to this therapy. No side-effects were noted in any patients. Conclusion:, Rebamipide enema therapy proved to be safe and useful in corticosteroid-refractory patients with the active distal type of UC. [source] The effect of hyaluronic acid on IL-1,-induced chondrocyte apoptosis in a rat model of osteoarthritisJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 12 2008Pang-Hu Zhou Abstract The purpose of this article was to study the effect of hyaluronic acid (HA) on chondrocyte apoptosis in a rat osteoarthritis in vitro model (exposure to IL-1,) and explore its mechanism. A rat in vitro model of osteoarthritis (OA) was established using 10 ng/mL IL-1, as a modulating and chondrocyte apoptosis inducing agent. Different doses of HA (10, 20, and 40 µg/mL) were added 1 h prior to the addition of IL-1, to a monolayer culture of freshly isolated juvenile rat chondrocytes. The ratio of apoptotic cell death was surveyed by Annexin V-FITC and propidium iodide double-labeling FACS analysis. The mitochondrial membrane potential of chondrocytes was evaluated by rhodamine-123 fluorescence. The mitochondrial function was evaluated through detecting the ATP production by a luciferase assay. The reverse transcription polymerase chain reaction (RT-PCR) was performed to measure mRNA expression levels of inducible oxide synthase (iNOS). HA could inhibit IL-1,-induced chondrocyte apoptosis in our cell culture model system. It was showed that addition of HA to the medium was able in a dose-dependent way to reduce the impairment of the mitochondrial membrane potential and to restore mitochondrial ATP production. This study shows that HA could suppress in a dose-dependent way chondrocyte apoptosis in our IL-1,-induced osteoarthritis model. The suppression of inflammatory cytokine activity within the joint might be one important mechanism of the clinical action of intraarticular injection of HA in the treatment of OA. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [source] Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndromePSYCHOPHYSIOLOGY, Issue 4 2010Andrea T. White Abstract Chronic fatigue syndrome (CFS) patients often report symptom flare (SF) for >24 h after moderate exercise (post-ex). We hypothesized that SF is linked to increases in circulating cytokines and CD40 Ligand (CD40L). In 19 CFS patients and 17 controls, mental and physical fatigue and pain symptom ratings were obtained together with serum for 11 cytokines and CD40L before and at 0.5, 8, 24, and 48 h post-ex. Before exercise, CFS had lower CD40L (p<.05) but similar cytokines versus controls. In subgroups based on SF at 48 h, high SF patients (n=11) increased in IL-1,, IL-12, IL-6, IL-8, IL-10, and IL-13 (p<.05) 8 h post-ex. Low SF patients (n=8) showed post-ex decreases in IL-10, IL-13, and CD40L, and controls decreased in IL-10, CD40L, and TNF, (p<.05). Thus, in CFS, cytokine activity may vary directly with SF, which may explain prior inconsistent findings. [source] Enhancement of natural killer (NK) cell cytotoxicity and induction of NK cell-derived interferon-gamma (IFN- ,) display different kinetics during experimental infection with Trypanosoma cruziCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2000C. Une Early immunological activation involves an initial phase of cytokine activity and involvement of cell types such as NK cells. Such early immune responses are often decisive in resolution of microbial infection. NK cells reduce parasitaemia and enhance survival in experimental Trypanosoma cruzi infection, although the nature of these protective effects is not well understood. In this study, a detailed analysis of innate cytokine induction in the absence and presence of NK cells during the first 8 days of infection was performed. Following intraperitoneal infection with a high dose of parasites, reverse transcriptase-polymerase chain reaction showed that splenic mRNA for IFN- , appeared as a peak 24 h after infection and then reappeared 2,3 days later. In NK-depleted animals the first peak of IFN- , was absent and the second wave was slightly delayed. mRNA for IL-12 and tumour necrosis factor-alpha (TNF- ,) as well as IFN- , protein in serum was only recorded 24 h after infection, at the same time as the IFN- , peak. NK depletion resulted in a small decrease of IL-12 mRNA levels, whereas TNF- , and IFN- , were not affected. NK cytotoxicity remained elevated throughout the 8 days and thus did not parallel the expression of IFN- , production by NK cells. We conclude that NK cell cytokine production and cytolytic activity play different roles in response to challenge with T. cruzi. [source] | ||||||||||