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IL-10 Expression (il-10 + expression)
Selected AbstractsIL-10 promoter haplotype influence on interferon treatment response in multiple sclerosisEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2005S. Wergeland The level of interleukin-10 (IL-10) expression is related to polymorphisms -1082 (G/A), -819 (T/C) and -592 (A/C) in the promoter region of the IL-10 gene, which constitute three haplotypes, GCC, ATA, and ACC. The ATA (a non-GCC) haplotype, which is associated with low IL-10 expression, has been shown to improve interferon (IFN) treatment response in hepatitis C. We analysed the distribution of IL-10 promoter haplotype combinations to determine whether they could influence initial IFN treatment response in 63 patients with relapsing-remitting multiple sclerosis (MS). The patients were grouped into non-GCC or GCC haplotypes, and the clinical and magnetic resonance imaging (MRI) disease activity was compared in the two groups. During the first 6 months of treatment, MS patients with non-GCC haplotypes experienced fewer new MRI T1-contrast enhancing lesions [0.77 ± 0.36 (SEM)] than patients with the GCC haplotype (2.45 ± 0.57) (P = 0.05, Mann-Whitney U test). No differences were detected on clinical disease activity. The results suggest an influence of IL-10 promoter polymorphisms on IFN treatment response in MS. [source] Response of lung ,, T cells to experimental sepsis in miceIMMUNOLOGY, Issue 1 2004Mark Hirsh Summary ,, T cells link innate and adaptive immune systems and may regulate host defence. Their role in systemic inflammation induced by trauma or infection (sepsis) is still obscured. The present study was aimed to investigate functions of lung ,, T cells and their response to experimental sepsis. Mice were subjected to caecal ligation and puncture (CLP) to induce sepsis and acute lung injury (ALI), or to the sham operation. Animals were killed 1, 4, and 7 days postoperatively; lungs were examined by histology, and isolated cells were studied by flow cytometry. Absolute number of ,, T cells progressively increased in lungs during sepsis, and reached a seven-fold increase at day 7 after CLP (3·84 ± 0·41 × 105/lung; P,=,0·0002 versus sham). A cellular dysfunction was revealed one day after CLP, as manifested by low cytolytic activity (22·3 ± 7·1%; P,<,0·05 versus sham), low interferon-, (IFN-,; 8·5 ± 2·5%; P,<,0·05 versus control) and interleukin-10 (IL-10) expression, and high tumour necrosis factor-, expression (19·5 ± 1·7%; P,<,0·05 versus control). The restoration of cytotoxicity, and increase in IFN-, and IL-10 expression was observed at day 7 of CLP-induced sepsis. In summary, our results demonstrate significant progressive accumulation of ,, T cells in lungs during CLP-induced ALI. The temporary functional suppression of lung ,, T cells found early after CLP may influence the outcome of sepsis, possibly being associated with uncontrolled inflammatory lung damage. [source] Interleukin-10 expression significantly correlates with minor CD8+ T-cell infiltration and high microvessel density in patients with gastric cancerINTERNATIONAL JOURNAL OF CANCER, Issue 8 2006Teruhisa Sakamoto Abstract We aimed to investigate the relationships between interleukin-10 (IL-10) expression and both the clinicopathological findings and prognoses in patients with gastric cancer and to compare IL-10 expression with microvessel (MV) density and CD8+ T lymphocyte infiltration to evaluate its effects on angiogenesis and immune responses in gastric cancer. IL-10 expression was determined in gastric cancer patients by reverse transcription-polymerase chain reaction (RT-PCR) or immunohistochemical procedures. Two of 7 normal gastric tissues showed IL-10 mRNA expression, while its expressions were confirmed in all advanced gastric carcinoma tissues examined (n = 11) by RT-PCR. Immunohistochemical staining demonstrated that IL-10 expression was detected in 52 (47.7%) of 109 cases. There was a close correlation between IL-10 expression and MV density. IL-10 expression inversely correlated with CD8+ T-lymphocyte infiltration. The prognoses of patients whose tumors expressed IL-10 were significantly worse than those of patients whose tumors did not express IL-10. Multivariate analysis indicated IL-10 expression was an independent prognostic factor. IL-10 might be associated with tumor progression by stimulating angiogenesis and suppressing immune responses in gastric cancer. © 2005 Wiley-Liss, Inc. [source] Inhibition of the p38 pathway upregulates macrophage JNK and ERK activities, and the ERK, JNK, and p38 MAP kinase pathways are reprogrammed during differentiation of the murine myeloid M1 cell lineJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2002J. Perry Hall Abstract Mitogen-activated protein (MAP) kinases have been implicated as important mediators of the inflammatory response. Here we report that c-Jun NH2 -terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 MAP kinase activities are reprogrammed during the IL-6 induced macrophage-like differentiation of the murine myeloid M1 cell line. Moreover, p38 inhibition upregulates JNK and ERK activity in M1 cells and in thioglycollate-elicited peritoneal exudate macrophages. IL-6-induced M1 differentiation also induces expression of the anti-inflammatory cytokine IL-10, and p38 inhibition potentiates this increase in IL-10 expression in an ERK-dependent manner. Thus, we speculate that during inflammatory conditions in vivo macrophage p38 may regulate JNK and ERK activity and inhibit IL-10 expression. These data highlight the importance of p38 in the molecular mechanisms of macrophage function. J. Cell. Biochem. 86: 1,11, 2002. © 2002 Wiley-Liss, Inc. [source] Suppression of proinflammatory cytokines and induction of IL-10 in human monocytes after coxsackievirus B3 infectionJOURNAL OF MEDICAL VIROLOGY, Issue 4 2001P. Hofmann Abstract Coxsackievirus B3 (CVB3) causes acute and chronic myocarditis, which is accompanied by an intense mononuclear leukocyte infiltration. Because myocardial tissue damage may either result from viral infections or from a dysregulated immune response, the susceptibility of human monocytes and macrophages to CVB3 was examined in this study with regard to virus replication, virus persistence, and release of cytokines. Monocytes were infected by CVB3 as shown by the intracellular appearance of plus- and minus-strand viral RNA, which was also capable of persisting for more than 10 days. Fresh monocytes were not permissive for full virus replication whereas monocyte-derived macrophages yielded a low amount of new viruses, which led to cell death. Although CVB3 infection induced the mRNA for the proinflammatory cytokines tumor necrosis factor-alpha (TNF-,), interleukin (IL)-1, and IL-6, only little cytokine production occurred. When infected monocytes were stimulated in addition by lipopolysaccharides (LPS), cytokine production was partially suppressed. In striking contrast, IL-10 expression was strongly and persistently induced by CVB3 on the mRNA and the protein level. These data show a dysregulated cytokine response in CVB3-exposed human monocytes and macrophages, which is characterized by a suppression of proinflammatory cytokines and a dominance of IL-10. This viral strategy may aid CVB3, causing chronic myocardiopathy. J. Med. Virol. 64:487,498, 2001. © 2001 Wiley-Liss, Inc. [source] Combined effect of IL-10 and TGF-,1 promoter polymorphisms as a risk factor for aspirin-intolerant asthma and rhinosinusitisALLERGY, Issue 8 2009S.-H. Kim Background:, It has been known that interleukin (IL)-10 promoter polymorphisms at ,1082A/G, ,819T/C and ,592A/C, may influence IL-10 expression and associate with asthma. Interleukin-10 facilitates the regulatory function of transforming growth factor (TGF)-,. The goal of this study was to investigate a gene,gene interaction between IL-10 and TGF-,1 polymorphisms in Korean asthmatics with aspirin hypersensitivity. Methods:, Single-nucleotide polymorphism genotyping of IL-10 and TGF-,1 genes was performed and the functional effect of the IL-10 polymorphisms was analysed applying a luciferase reporter assay and an electrophoretic mobility shift assay. Results:, Among the patients with asthma, polymorphism at ,1082A/G was significantly associated with the phenotype of aspirin-intolerant asthma, AIA (P = 0.007, Pc = 0.021). Moreover, a synergistic effect between the TGF-,1,509C/T and IL-10,1082A/G polymorphisms on the phenotype of AIA was noted; when stratified by the presence of rhinosinusitis, the frequency of rare alleles (the CT or TT genotype of TGF-,1,509C/T and AG or GG genotype of IL-10,1082A/G) was significantly higher in the patients with AIA (15.2%) when compared with those with ATA (6.3%, P = 0.031; odds ratio 4.111; 95% confidence interval 1.504,11.235). In an in vitro functional assay, the ,1082G reporter plasmid exhibited significantly greater promoter activity when compared with the ,1082A construct in Jurkat T cells (P = 0.011). Moreover, we found that the transcription factor Myc-associated zinc-finger protein preferentially bound the ,1082G allele. Conclusion:, Our results suggest that IL-10 promoter polymorphisms contribute to the development of AIA and that rhinosinusitis may interact genetically with TGF-,1. [source] Nasal endothelial interleukin-10 expression is negatively correlated with nasal symptoms after allergen provocationALLERGY, Issue 5 2009B. Muller Background:, Despite major efforts, factors that predict or correspond to the level of allergic symptoms remain elusive. Given our previous observations of mucosal interleukin-10 (IL-10) expression by local tissue cells and its described role as immune modulator, we hypothesized that, in allergic rhinitis, nasal mucosal IL-10 expression could influence the severity of symptoms. Methods:, In this study, we investigated endothelial IL-10 expression in nasal mucosa of healthy- and house dust mite allergic patients, both before and after provocation, and under nasal steroid therapy. Nasal turbinate biopsies were taken from healthy individuals as well as from house dust mite allergic patients, both before and after provocation. Allergic patients received fluticasone proprionate aqueous nasal spray or control treatment. In the allergic patients, endothelial IL-10 scores based on immunohistochemical stainings were correlated with allergic symptoms, measured by visual analog scores. Results:, At baseline, variable levels of endothelial IL-10 were detected in nasal biopsies. After nasal provocation, but not at baseline, endothelial IL-10 expression corresponded very closely to the allergic symptoms after allergen provocation. Low symptom scores were correlated with high endothelial IL-10 scores. This correlation disappeared after fluticason propionate treatment. Conclusions:, There is a large variation in the level of endothelial IL-10 expression both in healthy individuals and in house dust mite allergic patients. Endothelial IL-10 expression may affect local immune reactions resulting in reduced levels of allergic symptoms. [source] IL-10 Does not Play a Role in Cutaneous Photofrin® Photodynamic Therapy-induced Suppression of the Contact Hypersensitivity Response,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 6 2001Sandra O. Gollnick ABSTRACT Photodynamic therapy (PDT) treatment of both malignant and benign skin diseases has proven to be effective, and its use is increasing worldwide. However, preclinical studies using murine models have shown that PDT of the skin inhibits cell-mediated immune reactions, as measured by the suppression of the contact hypersensitivity (CHS) reaction. We have previously demonstrated that PDT enhances IL-10 expression in treated skin, and that the kinetics of induction of IL-10 is similar to the kinetics of suppression of systemic CHS reactions by cutaneous PDT. In the following report we have expanded upon these studies to demonstrate that cutaneous PDT, using Photofrin®, induces elevated levels of systemic IL-10 that persist for at least 28 days following treatment. The increase in systemic IL-10 correlates to a prolonged suppression of CHS of at least 28 days following cutaneous PDT. IL-10 has been implicated as the causative agent in the suppression of cell-mediated immune reactions by UVB and transdermal PDT. However, in the studies reported here we demonstrate that the suppression of CHS by cutaneous PDT occurs via an IL-10 independent mechanism, as administration of anti,IL-10 antibodies had no effect on the ability of PDT to induce CHS suppression. These results were further confirmed using IL-10 knockout (KO) mice. Cutaneous PDT of IL-10 KO mice resulted in CHS suppression that was not significantly different from suppression induced in wild-type mice. Thus, it appears as though IL-10 does not play a role in CHS suppression by cutaneous PDT. Suppression of cell-mediated immune reactions by UVB and transdermal PDT is reversible by IL-12, which is critical for the development of these reactions. We show that administration of exogenous IL-12 is also able to reverse CHS suppression induced by cutaneous PDT, suggesting that whereas suppression of cell-mediated immune reactions by UVB, transdermal PDT and cutaneous PDT occurs via different mechanisms, a common regulatory point exists. [source] ORIGINAL ARTICLE: The Role of TSP-1 on Decidual Macrophages Involved in the Susceptibility to Unexplained Recurrent Spontaneous AbortionAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2009Yan Jin Problem, To investigate the role of TSP-1 on decidual macrophages (DM,) in unexplained recurrent spontaneous abortion (RSA). Method of study, A total of 20 women undergoing artificial abortion in the first trimester and 10 patients with RSA were selected. (i) The expression of TSP-1 mRNA in deciduas was detected by real-time polymerase chain reaction; (ii) Flow cytometry was used to detect the percentage of positive TSP-1, CD36, CD47 markers on macrophages. (iii) Cytokine expression was measured by enzyme-linked immunosorbent spot-forming (ELISPOT) cell assay. Results, (i) The expression of TSP-1 mRNA on DM, in RSA was significantly decreased (P < 0.05). (ii) The increased expression of CD36 (P < 0.01) and the decreased expression of TSP1 (P < 0.01) were found on DM, of RSA. No different CD47 expression level on DM, was observed between two groups. (iii)The expression of IL-10 in DM, of RSA patients was decreased significantly compared with that of controls (P < 0.05). When adding TSP1 into culture medium, there was no change in IFN-, expression, but increased IL-10 (P < 0.05) expression in DM, of RSA patients was observed. The expression of IL-10 was decreased significantly in DM, from controls when adding anti-TSP-1 antibody to culture medium (P < 0.05). Conclusion, TSP-1 on DM, could influence IL-10 expression as Th2 cytokines. The abnormal expression of TSP-1 could make some women undergo pregnancy loss. [source] Long,term culture of multibacillary leprosy macrophages isolated from skin lesions: a new model to study Mycobacterium leprae,human cell interactionBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2007D.F. Moura Summary Background, Leprosy is characterized by a disease spectrum having two polar clinical forms dependent on the presence or not of cell-mediated immunity. In the tuberculoid forms, granuloma-activated macrophages kill Mycobacterium leprae in conjunction with a Th1 response while, in multibacillary (MB) lesions, M. leprae nonactivated macrophages infiltrate the nerves and internal organs together with a Th2 response. The functional properties and activation pathways of macrophages isolated from patients with MB leprosy remain only partially understood. Objectives, To establish an ex vivo methodology capable of evaluating the activation pathways, grade and fate of cultured macrophages isolated from MB lesions. Methods, Skin biopsies from patients with borderline tuberculoid, bordeline lepromatous and lepromatous leprosy (LL) were characterized by immunohistochemistry and transcriptional analysis. To isolate inflammatory cells, a portion of the samples was submitted to enzymatic digestion. These same cells, maintained in culture for a minimum 7-day period, were characterized morphologically and via flow cytometry at different culture time points. Cytokine [interferon (IFN)-,, tumour necrosis factor (TNF)-, and interleukin (IL)-10] mRNA levels were quantified by real-time polymerase chain reaction and protein secretion in the culture supernatants was measured by enzyme-linked immunosorbent assay and the nitric oxide levels by Griess reagent. Results, RNA expression in tuberculoid and MB lesions showed the profile expected of characteristic Th1 and Th2 responses, respectively. The inflammatory cells in all biopsies were successfully isolated. Although the number of cells varied between biopsies, it was highest in LL biopsies. The frequency of isolated CD14+ and CD3+ cells measured by flow cytometry correlated with the percentages of macrophages and lymphocytes in the lesions. Throughout the culture period, CD68+ macrophages showed morphological changes. A progressive increase in cell number and reduction of infected cells were perceptible in the cultures. In contrast to the biopsies, TNF-,, IFN-, and IL-10 expression in the tuberculoid and MB leprosy cells in 24-h culture and the cytokine levels in the supernatants did not differ significantly. During the culture period, cytokine expression in the MB cells progressively declined, whereas, from days 1 to 7, nitrite levels progressively increased. After day 40, the remaining macrophages were able to ingest fluorescein isothiocyanate-labelled M. leprae. These data need to be confirmed. Conclusions, This study confirmed the feasibility of obtaining ex vivo macrophages from leprosy lesions and keeping them in long-term culture. This procedure may open new pathways to studying the interaction between M. leprae and human macrophages, which might, in turn, lead to the development of therapeutic tools capable of overcoming the specific anergy found in patients with MB leprosy. [source] Surfactant protein D deficiency influences allergic immune responsesCLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2004B. Schaub Summary Background The collectin surfactant protein D (SP-D) confers protection against pulmonary infection and inflammation. Recent data suggest a role for SP-D in the modulation of allergic inflammation. Objective The aim of this study is to characterize the immune responses of SP-D-deficient (SP-D,/,) mice in a kinetic model of allergic inflammation. We determined whether allergic parameters were enhanced in SP-D,/, mice in vivo. Further, we examined whether functional immune responses in vitro such as lymphocyte proliferation (LP) and cytokine production were modulated in the absence of SP-D. Methods In vivo, wild-type (WT) and SP-D,/, mice were sensitized and challenged with the allergen ovalbumin (OVA) and assessed for allergic parameters (bronchoalveolar lavage (BAL) eosinophils, IL-13 production, pulmonary IFN-,, IL-10 expression) at early time points (1 and 3 days of challenge) in comparison with late time points (7 days of challenge). In vitro, spleen cells from WT and SP-D,/, mice were stimulated with the mitogen concanavalin A (ConA) and lipid A (LpA) and analysed for LP, IL-13 and IFN-, production. Toll-like receptor 4 (TLR4), ligand for LpA, was assessed by mRNA expression and immunohistochemistry in vivo. Results Following allergen exposure in vivo, SP-D,/, mice expressed higher BAL eosinophils and IL-13 concentrations and lower IFN-, expression at early time points compared with WT mice. IL-10 expression was increased at early time points in SP-D,/, compared with WT mice. Allergen-induced TLR4 expression was increased in WT, but not in SP-D,/, mice. After stimulation with LpA and ConA in vitro LP was increased and IFN-, concentration was decreased in SP-D,/, mice. Conclusion SP-D may be critical for the modulation of early stages of allergic inflammation in vivo. [source] | |||||||||||||||||||||||||