scholarly journals Ets-1, a functional cofactor of T-bet, is essential for Th1 inflammatory responses

2005 ◽  
Vol 201 (4) ◽  
pp. 615-626 ◽  
Author(s):  
Roland Grenningloh ◽  
Bok Yun Kang ◽  
I-Cheng Ho
Keyword(s):  
Inflammatory Responses ◽  
Interleukin 10 ◽  
Interferon Γ ◽  
Th1 Cells ◽  
Reciprocal Regulation ◽  
Unique Role ◽  
High Level ◽  
Very High

To mount an effective type 1 immune response, type 1 T helper (Th1) cells must produce inflammatory cytokines and simultaneously suppress the expression of antiinflammatory cytokines. How these two processes are coordinately regulated at the molecular level is still unclear. In this paper, we show that the proto-oncogene E26 transformation–specific-1 (Ets-1) is necessary for T-bet to promote interferon-γ production and that Ets-1 is essential for mounting effective Th1 inflammatory responses in vivo. In addition, Ets-1–deficient Th1 cells also produce a very high level of interleukin 10. Thus, Ets-1 plays a crucial and unique role in the reciprocal regulation of inflammatory and antiinflammatory Th responses.

scholarly journals Inhibition of Interleukin 10 Signaling after Fc Receptor Ligation and during Rheumatoid Arthritis

2003 ◽  
Vol 197 (11) ◽  
pp. 1573-1583 ◽  
Author(s):  
Jong-Dae Ji ◽  
Ioannis Tassiulas ◽  
Kyung-Hyun Park-Min ◽  
Ani Aydin ◽  
Ingrid Mecklenbräuker ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Complexes ◽  
Inflammatory Responses ◽  
Fc Receptors ◽  
Interleukin 10 ◽  
Interferon Γ ◽  
Fc Receptor ◽  
Receptor Expression ◽  
Inflammatory Factors

Interleukin-10 (IL-10) is a potent deactivator of myeloid cells that limits the intensity and duration of immune and inflammatory responses. The activity of IL-10 can be suppressed during inflammation, infection, or after allogeneic tissue transplantation. We investigated whether inflammatory factors suppress IL-10 activity at the level of signal transduction. Out of many factors tested, only ligation of Fc receptors by immune complexes inhibited IL-10 activation of the Jak-Stat signaling pathway. IL-10 signaling was suppressed in rheumatoid arthritis joint macrophages that are exposed to immune complexes in vivo. Activation of macrophages with interferon-γ was required for Fc receptor–mediated suppression of IL-10 signaling, which resulted in diminished activation of IL-10–inducible genes and reversal of IL-10–dependent suppression of cytokine production. The mechanism of inhibition involved decreased cell surface IL-10 receptor expression and Jak1 activation and was dependent on protein kinase C delta. These results establish that IL-10 signaling is regulated during inflammation and identify Fc receptors and interferon-γ as important regulators of IL-10 activity. Generation of macrophages refractory to IL-10 can contribute to pathogenesis of inflammatory and infectious diseases characterized by production of interferon-γ and immune complexes.

scholarly journals Role of Vitamin D in Premature Atherosclerosis in Adolescents Type 1 Diabetes through Transforming Growth Factor-β1, Interferon-γ, Interleukin-10, and Interleukin-17

2020 ◽  
Vol 8 (B) ◽  
pp. 738-746
Author(s):  
Haryudi Aji Cahyono ◽  
Wisnu Barlianto ◽  
Dian Handayani ◽  
Handono Kalim
Keyword(s):  
Vitamin D ◽  
Type 1 Diabetes ◽  
Transforming Growth Factor ◽  
Interleukin 10 ◽  
Interferon Γ ◽  
Transforming Growth Factor Β1 ◽  
Premature Atherosclerosis ◽  
Ifn Γ ◽  
Tgf Β1

BACKGROUND: Cardiovascular disease (CVD) is one the cause of mortality in patients with type 1 diabetes (T1D). The development of CVD is mainly triggered by atherosclerosis, which is associated with the inflammatory process. AIM: The current study was aimed to investigate the association of Vitamin D level and premature atherosclerosis in adolescents with T1D, mainly through the regulation of various cytokines (interferon-γ [IFN-γ], IL-17, interleukin-10 [IL-10], and transforming growth factor-β1 [TGF-β1]). METHODS: This study was designed as a cross-sectional study involving 40 T1D and 40 healthy control who came to the outpatient clinic, Saiful Anwar Hospital, Malang, Indonesia, within the study period (January 2019-July 2019). RESULTS: Our data demonstrated that the IFN-γ and IL-17 levels were significantly higher (p < 0.001), whereas the TGF-β1 and IL-10 levels were significantly lower (p < 0.001) in T1D group compared with control. Furthermore, T1D also has higher carotid intima-media thickness (cIMT) value and lower flow-mediated dilatation (FMD) value compared to the control group (p < 0.001). Level of 25(OH)D3 was strongly associated with reduced cIMT and elevated FMD (p < 0.005). The direct effect of 25(OH)D3 on cIMT and FMD was higher than the indirect effect of Vitamin D through TGF-β1, IL-10, IL-17, and IFN-γ. The cutoff value of 25(OH)D3 levels for the risk of atherosclerosis was 12.8 ng/dL (sensitivity 85.7% and specificity 86.7%). CONCLUSION: The level of Vitamin D in the T1D group was significantly lower than those in healthy children and Vitamin D deficiency substantially influences the formation of premature atherosclerosis.

scholarly journals Resolution of a chronic viral infection after interleukin-10 receptor blockade

2006 ◽  
Vol 203 (11) ◽  
pp. 2461-2472 ◽  
Author(s):  
Mette Ejrnaes ◽  
Christophe M. Filippi ◽  
Marianne M. Martinic ◽  
Eleanor M. Ling ◽  
Lisa M. Togher ◽  
...  
Keyword(s):  
T Cells ◽  
Viral Infections ◽  
Neutralizing Antibody ◽  
Interleukin 10 ◽  
Interferon Γ ◽  
Lymphocytic Choriomeningitis ◽  
Persistently Infected ◽  
Functional Inactivation ◽  
Cellular Immune

A defining characteristic of persistent viral infections is the loss and functional inactivation of antiviral effector T cells, which prevents viral clearance. Interleukin-10 (IL-10) suppresses cellular immune responses by modulating the function of T cells and antigen-presenting cells. In this paper, we report that IL-10 production is drastically increased in mice persistently infected with lymphocytic choriomeningitis virus. In vivo blockade of the IL-10 receptor (IL-10R) with a neutralizing antibody resulted in rapid resolution of the persistent infection. IL-10 secretion was diminished and interferon γ production by antiviral CD8+ T cells was enhanced. In persistently infected mice, CD8α+ dendritic cell (DC) numbers declined early after infection, whereas CD8α− DC numbers were not affected. CD8α− DCs supported IL-10 production and subsequent dampening of antiviral T cell responses. Therapeutic IL-10R blockade broke the cycle of IL-10–mediated immune suppression, preventing IL-10 priming by CD8α− DCs and enhancing antiviral responses and thereby resolving infection without causing immunopathology.

scholarly journals Defining tissue- and disease-associated macrophages using a transcriptome-based classification model

2019 ◽  
Author(s):  
Hung-Jen Chen ◽  
Andrew Y.F. Li Yim ◽  
Guillermo R. Griffith ◽  
Wouter J. de Jonge ◽  
Marcel M.A.M. Mannens ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Interleukin 10 ◽  
Interferon Γ ◽  
Classification Model ◽  
Chronic Obstructive ◽  
Activated Macrophages ◽  
Obstructive Pulmonary Disease ◽  
Disease Specific

AbstractMacrophages are heterogeneous multifunctional leukocytes which are regulated in a tissue-and disease-specific context. Many different studies have been published using in vitro macrophage models to study disease. Here, we aggregated public expression data to define consensus expression profiles for eight commonly-used in vitro macrophage models. Altogether, we observed well-known but also novel markers for different macrophage subtypes. Using these data we subsequently built the classifier macIDR, capable of distinguishing macrophage subsets with high accuracy (>0.95). This classifier was subsequently applied to transcriptional profiles of tissue-isolated and disease-associated macrophages to specifically define macrophage characteristics in vivo. Classification of these in vivo macrophages showed that alveolar macrophages displayed high resemblance to interleukin-10 activated macrophages, whereas macrophages from patients with chronic obstructive pulmonary disease patients displayed a drop in interferon-γ signature. Adipose tissue-derived macrophages were classified as unstimulated macrophages, but resembled LPS-activated macrophages more in diabetic-obese patients. Finally, rheumatoid arthritic synovial macrophages showed characteristics of both interleukin-10 or interferon-γ signatures. Altogether, our results suggest that macIDR is capable of identifying macrophage-specific changes as a result of tissue-and disease-specific stimuli and thereby can be used to better define and model populations of macrophages that contribute to disease.

scholarly journals Effect of the synthesis of rice non-symbiotic hemoglobins 1 and 2 in the recombinant Escherichia coli TB1 growth

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 1053
Author(s):  
Emma Álvarez-Salgado ◽  
Raúl Arredondo-Peter
Keyword(s):  
Tertiary Structure ◽  
Biological Function ◽  
Equilibrium Constants ◽  
Dissociation Rate ◽  
Growth Effect ◽  
Soybean Leghemoglobin ◽  
Very High

Non-symbiotic hemoglobins (nsHbs) are widely distributed in land plants, including rice. These proteins are classified into type 1 (nsHbs-1) and type 2. The O2-affinity of nsHbs-1 is very high mostly because of an extremely low O2-dissociation rate constant resulting in that nsHbs-1 apparently do not release O2 after oxygenation. Thus, it is possible that the in vivo function of nsHbs-1 is other than O2-transport. Based on the properties of multiple Hbs it was proposed that nsHbs-1 could play diverse roles in rice organs, however the in vivo activity of rice nsHbs-1 has been poorly analyzed. An in vivo analysis for rice nsHbs-1 is essential to elucidate the biological function(s) of these proteins. Rice Hb1 and Hb2 are nsHbs-1 that have been generated in recombinant Escherichia coli TB1. The rice Hb1 and Hb2 amino acid sequence, tertiary structure and rate and equilibrium constants for the reaction of O2 are highly similar. Thus, it is possible that rice Hb1 and Hb2 function similarly in vivo. As an initial approach to test this hypothesis we analyzed the effect of the synthesis of rice Hb1 and Hb2 in the recombinant E. coli TB1 growth. Effect of the synthesis of the O2-carrying soybean leghemoglobin a, cowpea leghemoglobin II and Vitreoscilla Hb in the recombinant E. coli TB1 growth was also analyzed as an O2-carrier control. Our results showed that synthesis of rice Hb1, rice Hb2, soybean Lba, cowpea LbII and Vitreoscilla Hb inhibits the recombinant E. coli TB1 growth and that growth inhibition was stronger when recombinant E. coli TB1 synthesized rice Hb2 than when synthesized rice Hb1. These results suggested that rice Hb1 and Hb2 could function differently in vivo.

scholarly journals Interleukin-10 and Antigen-Presenting Cells Actively Suppress Th1 Cells in BALB/c Mice Infected with the Filarial Parasite Brugia pahangi

1999 ◽  
Vol 67 (4) ◽  
pp. 1599-1605 ◽  
Author(s):  
Julie Osborne ◽  
Eileen Devaney
Keyword(s):  
Interleukin 10 ◽  
Interleukin 4 ◽  
Th1 Cells ◽  
Spleen Cells ◽  
Third Stage ◽  
Antigen Presenting ◽  
Th1 Cytokines

ABSTRACT Infection with the third-stage larvae (L3) of the filarial nematodeBrugia results in a Th2-biased immune response in mice and humans. Previously we have shown that the production of interleukin 4 (IL-4) is critical for down-regulating polyclonal Th1 responses in L3-infected mice. However, the in vitro neutralization of IL-4 did not fully recover the defective polyclonal Th1 responses, nor did it result in the production of any antigen (Ag)-specific Th1 cytokines, suggesting that perhaps infection with L3 does not result in priming of Th1 cells in vivo. In this study, we analyzed the role of IL-10 and Ag-presenting cells (APCs) in the spleen as additional factors controlling the Th2 bias in infected mice. Our data show that IL-10 and APCs also contribute to the suppression of mitogen-driven Th1 responses of spleen cells from infected mice. In addition, the neutralization of IL-10 or the replacement of the resident APC population from spleen cell cultures resulted in the production of Ag-specific Th1 cytokines. Irradiated spleen cells from either L3-infected or uninfected mice were able to restore Ag-specific Th1 responses in vitro. Therefore, it appears that Brugia-reactive Th1 cells are primed following infection with L3, but are actively suppressed in vivo by a mechanism that involves IL-10 and the resident APC population, but not IL-4. These results indicate that a complex interplay of cytokines and cell populations underscores the Th2-polarized response in L3-infected mice.

scholarly journals Association of interferon-γ and interleukin 10 genotypes and serum levels with partial clinical remission in type 1 diabetes

2006 ◽  
Vol 145 (3) ◽  
pp. 480-484 ◽  
Author(s):  
B. Z. Alizadeh ◽  
P. Hanifi-Moghaddam ◽  
P. Eerligh ◽  
A. R. van der Slik ◽  
H. Kolb ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Clinical Remission ◽  
Serum Levels ◽  
Interleukin 10 ◽  
Interferon Γ

scholarly journals Heat-killed Tsukamurella inchonensis reduces lipopolysaccharide-induced inflammatory responses in activated murine peritoneal macrophages

2017 ◽  
Vol 62 (No. 12) ◽  
pp. 668-673 ◽  
Author(s):  
K. Nofouzi ◽  
M. Aghapour ◽  
B. Baradaran ◽  
GH Hamidian ◽  
P. Zare ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Peritoneal Macrophages ◽  
Interferon Γ ◽  
No Production ◽  
Griess Reaction ◽  
Indirect Technique ◽  
Factor Α ◽  
Mouse Peritoneal Macrophages

Tsukamurella inchonensis (T. inchonensis) is an aerobic species of Actinomycetales which has immunomodulatory activities when used as a suspension of killed bacilli. Here, the effects of T. inchonensis on lipopolysaccharide-induced inflammatory responses in mouse peritoneal macrophages have been examined. Peritoneal macrophages were harvested by lavaging with ice cold phosphate-buffered saline. Macrophages acquired from mice treated with different doses of T. inchonensis for seven days were cultured with 20 U/ml interferon-γ and 10 µg/ml lipopolysaccharide for in vivo assays. Nitrite levels were measured by using the diazotization method based on the Griess reaction, an indirect technique to determine nitric oxide (NO) production. T. inchonensis inhibited lipopolysaccharide-stimulated NO production in mouse peritoneal macrophages from mice previously exposed to concentrations of 108 and 5 × 10<sup>7</sup> CFU per flask. Also, T. inchonensis decreased lipopolysaccharide-induced production of pro-inflammatory cytokines, including interleukin-6 and tumor necrosis factor-α. Thus, it can be concluded that T. inchonensis is a powerful inhibitor of lipopolysaccharide-induced NO production in activated murine macrophages, and T. inchonensis may be useful as a novel agent for chemoprevention in inflammatory diseases.

Cardioprotective actions of endogenous IL-10 are independent of iNOS

2001 ◽  
Vol 281 (1) ◽  
pp. H48-H52 ◽  
Author(s):  
Steven P. Jones ◽  
Steven D. Trocha ◽  
David J. Lefer
Keyword(s):  
Myocardial Ischemia ◽  
Inflammatory Responses ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Myocardial Necrosis ◽  
Interleukin 10 ◽  
Wild Type ◽  
Tissue Samples ◽  
Cardioprotective Effects

Myocardial ischemia-reperfusion (I/R) is a well-known stimulus for acute inflammatory responses that promote cell death and impair pump function. Interleukin-10 (IL-10) is an endogenous, potent anti-inflammatory cytokine. Recently, it has been proposed that IL-10 inhibits inducible nitric oxide synthase (iNOS) activity after myocardial I/R and consequently exerts cardioprotective effects. However, whether this actually occurs remains unclear. To test this hypothesis, we utilized iNOS-deficient (−/−), IL-10 −/−, and IL-10/iNOS −/− mice to examine the potential mechanism of IL-10-mediated cardioprotection after myocardial I/R. Wild-type, iNOS −/−, IL-10 −/−, and IL-10/iNOS −/− mice were subjected to in vivo myocardial ischemia (30 min) and reperfusion (24 h). Deficiency of iNOS alone did not significantly alter the extent of myocardial necrosis compared with wild-type mice. We found that deficiency of IL-10 resulted in a significantly ( P < 0.05) larger infarct size than that in wild-type hearts. Interestingly, deficiency of both IL-10 and iNOS yielded significantly ( P < 0.01) larger myocardial infarct sizes compared with wild-type animals. Histological examination of myocardial tissue samples revealed augmented neutrophil infiltration into the I/R myocardium of IL-10 −/− and IL-10/iNOS −/− mice compared with hearts of wild-type mice. These results demonstrate that 1) deficiency of endogenous IL-10 exacerbates myocardial injury after I/R; 2) the cardioprotective effects of IL-10 are not dependent on the presence or absence of iNOS; and 3) deficiency of IL-10 enhances the infiltration of neutrophils into the myocardium after I/R.

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