Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 502
Filtrar
1.
J Immunol ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38949522

RESUMO

The Krebs cycle enzyme aconitate decarboxylase 1 (ACOD1) mediates itaconate synthesis in monocytes and macrophages. Previously, we reported that administration of 4-octyl itaconate to lupus-prone mice abrogated immune dysregulation and clinical features. In this study, we explore the role of the endogenous ACOD1/itaconate pathway in the development of TLR7-induced lupus (imiquimod [IMQ] model). We found that, in vitro, ACOD1 was induced in mouse bone marrow-derived macrophages and human monocyte-derived macrophages following TLR7 stimulation. This induction was partially dependent on type I IFN receptor signaling and on specific intracellular pathways. In the IMQ-induced mouse model of lupus, ACOD1 knockout (Acod1-/-) displayed disruptions of the splenic architecture, increased serum levels of anti-dsDNA and proinflammatory cytokines, and enhanced kidney immune complex deposition and proteinuria, when compared with the IMQ-treated wild-type mice. Consistent with these results, Acod1-/- bone marrow-derived macrophages treated in vitro with IMQ showed higher proinflammatory features. Furthermore, itaconate serum levels in systemic lupus erythematosus patients were decreased compared with healthy individuals, in association with disease activity and specific perturbed cardiometabolic parameters. These findings suggest that the ACOD1/itaconate pathway plays important immunomodulatory and vasculoprotective roles in systemic lupus erythematosus, supporting the potential therapeutic role of itaconate analogs in autoimmune diseases.

2.
Rev Esp Geriatr Gerontol ; 59(6): 101527, 2024 Jul 03.
Artigo em Espanhol | MEDLINE | ID: mdl-38964263

RESUMO

BACKGROUND AND OBJECTIVES: The objective is to describe the demographic, clinical, functional characteristics and outcomes of older adult patients hospitalized in the acute unit of the San Ignacio University Hospital (HUSI). METHODS: Descriptive, cross-sectional observational study, based on the review of the medical records of patients hospitalized in the Geriatrics Unit of the HUSI during the period 2019-2021. VARIABLES: Demographics, comorbidities, baseline situation, main cause of entry and outcomes. The diagnosis of geriatric syndromes was made through the Barthel index, the Lawton and Brody scale, FRAIL scale, mini nutritional assessment short form and Confusion Assessment Method criteria. RESULTS: A total of 4601 patients were analyzed, whose average age was 83years (56.2% women). 72.4% had some degree of dependency for basic activities of daily living, 90.8% had some degree of dependency for instrumental activities of daily living, 32.2% had malnutrition, 15. 7% falls, 9.9% oropharyngeal dysphagia, 32.2% frailty, 28.1% delirium, 54.1% previous dementia. The main comorbidities presented were arterial hypertension, chronic obstructive pulmonary disease and diabetes. 2.9% had some complication during their hospitalization, 10.8% died, and the hospital stay was 5days. CONCLUSION: Older adult patients admitted to the acute unit of the HUSI have a high frequency of dependency, dementia and nutritional disturbances.

3.
Insects ; 15(6)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38921131

RESUMO

Hybrid rice results from crossing a male-sterile line (the A line) with a pollen doner (the restorer or R line). In 3-line hybrid breeding systems, a fertile B line is also required to maintain A line populations. Heterosis is defined as a condition of traits whereby the hybrid exceeds the average of the parental lines. Heterobeltiosis is where the hybrid exceeds both parents. Hybrid rice may display heterosis/heterobeltiosis for growth, yield and resistance to herbivores, among other traits. In a greenhouse experiment, we assessed the frequency of heterosis for resistance to the brown planthopper (Nilaparvata lugans (BPH)), whitebacked planthopper (Sogatella furcifera (WBPH)) and yellow stemborer (Scirpophaga incertulas (YSB)) in eight hybrids under varying soil nitrogen conditions. We also assessed plant biomass losses due to herbivore feeding as an approximation of tolerance (the plant's capacity to compensate for damage). Nitrogen reduced resistance to all three herbivores but was also associated with tolerance to WBPH and YSB based on improved plant survival, growth and/or yields. Plant biomass losses per unit weight of WBPH also declined under high nitrogen conditions for a number of hybrids, and there were several cases of overcompensation in rice for attacks by this herbivore. There was one case of nitrogen-related tolerance to BPH (increased grain yield) for a hybrid line with relatively high resistance, likely due to quantitative traits. Heterosis and heterobeltiosis were not essential to produce relatively high herbivore resistance or tolerance across hybrids.

5.
Nat Methods ; 21(5): 846-856, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38658646

RESUMO

CD4+ T cells recognize peptide antigens presented on class II major histocompatibility complex (MHC-II) molecules to carry out their function. The remarkable diversity of T cell receptor sequences and lack of antigen discovery approaches for MHC-II make profiling the specificities of CD4+ T cells challenging. We have expanded our platform of signaling and antigen-presenting bifunctional receptors to encode MHC-II molecules presenting covalently linked peptides (SABR-IIs) for CD4+ T cell antigen discovery. SABR-IIs can present epitopes to CD4+ T cells and induce signaling upon their recognition, allowing a readable output. Furthermore, the SABR-II design is modular in signaling and deployment to T cells and B cells. Here, we demonstrate that SABR-IIs libraries presenting endogenous and non-contiguous epitopes can be used for antigen discovery in the context of type 1 diabetes. SABR-II libraries provide a rapid, flexible, scalable and versatile approach for de novo identification of CD4+ T cell ligands from single-cell RNA sequencing data using experimental and computational approaches.


Assuntos
Linfócitos T CD4-Positivos , Epitopos de Linfócito T , Antígenos de Histocompatibilidade Classe II , Linfócitos T CD4-Positivos/imunologia , Epitopos de Linfócito T/imunologia , Animais , Antígenos de Histocompatibilidade Classe II/imunologia , Antígenos de Histocompatibilidade Classe II/química , Camundongos , Humanos , Diabetes Mellitus Tipo 1/imunologia , Peptídeos/imunologia , Peptídeos/química , Apresentação de Antígeno/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Camundongos Endogâmicos NOD , Análise de Célula Única/métodos
6.
medRxiv ; 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38605883

RESUMO

Objective: The Krebs cycle enzyme Aconitate Decarboxylase 1 (ACOD1) mediates itaconate synthesis in myeloid cells.. Previously, we reported that administration of 4-octyl itaconate abrogated lupus phenotype in mice. Here, we explore the role of the endogenous ACOD1/itaconate pathway in the development of murine lupus as well as their relevance in premature cardiovascular damage in SLE. Methods: We characterized Acod1 protein expression in bone marrow-derived macrophages and human monocyte-derived macrophages, following a TLR7 agonist (imiquimod, IMQ). Wild type and Acod1-/- mice were exposed to topical IMQ for 5 weeks to induce an SLE phenotype and immune dysregulation was quantified. Itaconate serum levels were quantified in SLE patients and associated to cardiometabolic parameters and disease activity. Results: ACOD1 was induced in mouse bone marrow-derived macrophages (BMDM) and human monocyte-derived macrophages following in vitro TLR7 stimulation. This induction was partially dependent on type I Interferon receptor signaling and specific intracellular pathways. In the IMQ-induced mouse model of lupus, ACOD1 knockout (Acod1-/-) displayed disruptions of the splenic architecture, increased serum anti-dsDNA and proinflammatory cytokine levels, enhanced kidney immune complex deposition and proteinuria, when compared to the IMQ-treated WT mice. Consistent with these results, Acod1-/- BMDM exposed to IMQ showed higher proinflammatory features in vitro. Itaconate levels were decreased in SLE serum compared to healthy control sera, in association with specific perturbed cardiometabolic parameters and subclinical vascular disease. Conclusion: These findings suggest that the ACOD1/itaconate pathway plays important immunomodulatory and vasculoprotective roles in SLE, supporting the potential therapeutic role of itaconate analogs in autoimmune diseases.

7.
Small Methods ; : e2301215, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38678536

RESUMO

Tailoring a material's surface with hierarchical structures from the micro- to the nanoscale is key for fabricating highly sensitive detection platforms. To achieve this, the fabrication method should be simple, inexpensive, and yield materials with a high density of surface features. Here, using benchtop fabrication techniques, gold surfaces with hierarchically structured roughness are generated for sensing applications. Hierarchical gold electrodes are prepared on pre-stressed polystyrene substrates via electroless deposition and amperometric pulsing. Electrodes fabricated using 1 mm H[AuCl4] and roughened with 80 pulses revealed the highest electroactive surface area. These electrodes are used for enzyme-free detection of glucose in the presence of bovine serum albumin and achieved a limit of detection of 0.36 mm, below glucose concentrations in human blood. The surfaces nanoroughened with 100 pulses also showed excellent surface-enhanced Raman scattering (SERS) response for the detection of rhodamine 6G, with an enhancement factor of ≈2 × 106 compared to detection in solution, and for the detection of a self-assembled monolayer of thiophenol, with an enhancement factor of ≈30 compared to the response from microstructured gold surfaces. It is envisioned that the simplicity and low fabrication cost of these gold-roughened structures will expedite the development of electrochemical and SERS sensing devices.

9.
Int J Phytoremediation ; : 1-8, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38529629

RESUMO

Many contaminated tailings throughout the world cause environmental and human-health related problems due to air and water drift. Tailing phytostabilization is a promising solution, but only certain plant species may tolerate and grow in these contaminated areas. We analyzed the chemical properties of a vegetated and unvegetated area in a tailing site in Central Chile. In addition, in the vegetated area we analyzed the metals content of roots, stems, and foliage in 41-years old plantations of Pinus radiata, Acacia dealbata, and Eucalyptus globulus (the only three species that survived from a total of 34 species planted), and determined height (H), and diameter at breast height (DBH). The results indicated that, except for pH, Se, Pb, and organic matter, all components (nutrients and metals) were two- to three- fold lower in the vegetated tailing compared to that of the unvegetated tailing. The analysis of plant tissues indicated that Cu was higher in the roots of P. radiata (2,073 mg kg-1) and lower in the stems of the same species (4.1 mg kg-1). However, the ability to take up and transport Cu to the shoots was higher in A. dealbata and lower in P. radiata (bioaccumulation factor of 0.19 and 0.06, respectively).


Here we present results for the first long-term phytostabilization project of copper mine tailings in Chile. From the 34 native and exotic species established in 1980 in a mine tailing disposal site with 1,000 mg Cu kg−1, only the exotic Pinus radiata, Acacia dealbata and Eucalyptus globulus were able to survive and adapt to the tailing conditions the last 41 years. This corroborates their potential for the future phytostabilization of copper mine wastes.

10.
Insects ; 15(3)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38535360

RESUMO

Three-line hybrid rice is produced by crossing male sterile (A line) rice with a fertility-restorer (R line). Fertile lines (B lines) are also required to maintain A line seed for breeding programs. We used a range of hybrids and their parental lines to assess the frequency and nature of heterosis for resistance to the whitebacked planthopper (Sogatella furcifera), brown planthopper (Nilaparvata lugens) and yellow stemborer (Scirpophaga incertulas). Heterosis is defined as trait improvement above the average of the parental lines as a result of outbreeding. Based on the results from a greenhouse study that challenged hybrids and their parental lines with each herbivore species, we found that susceptibility to planthoppers was associated with one of the eight A lines tested, but resistance was improved by crossing with a relatively resistant restorer. Higher frequencies of heterosis for susceptibility in comparisons between hybrids and their B lines suggest that susceptibility was not related to the cytoplasmic genomes of the associated sterile A lines. Furthermore, because none of the parental lines possessed currently effective resistance genes, improved resistance against planthoppers was probably due to quantitative resistance. In a related field trial, hybrids had generally higher yields than their fertile parents and often produced larger grain; however, they were often more susceptible to stemborers, leaffolders (Cnaphalocrocis medinalis) and other caterpillars (Rivula atimeta). This was largely a consequence of hybrid heterosis for plant biomass and was strongly affected by crop duration. We make a series of recommendations to improve hybrid breeding to reduce the risks of herbivore damage.

12.
Sports Med Int Open ; 8: a21876974, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38312927

RESUMO

Brown adipose tissue (BAT) helps control body weight and is inversely correlated with body fat, but it is unclear whether it is subcutaneous adipose tissue (SAT) or visceral adipose tissue (VAT) that is related to BAT activation. The presented study aimed to verify the relation of SAT and VAT on BAT activation through infrared thermography (IRT) and cold stimulation in adult women. Forty women were evaluated in body composition and skin temperature (Tskin) acquisition by IRT. Student's independent t-test, Pearson's correlation, and two-way repeated measures ANOVA with Tukey post-hoc were applied. Women with low amounts of SAT and VAT had a significant increase in supraclavicular Tskin (SCVT). Medium negative degrees of linear variation were found before and after cold stimulation between SCVT, SAT and VAT. A significant effect of the moment factor and the group factor on the SCVT between subjects divided into the groups were pointed out. No difference was found in the relation between SAT, VAT, and BAT in adult women, pointing out that both types of fat are equally related. These results can help clinical practice understand clearly, through IRT, that the high accumulation of SAT and VAT can impair the activation of BAT and hinder the loss of weight in women.

13.
Adv Healthc Mater ; 13(13): e2303288, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38349615

RESUMO

Cardiovascular diseases are a leading cause of mortality and pose a significant burden on healthcare systems worldwide. Despite remarkable progress in medical research, the development of effective cardiovascular drugs has been hindered by high failure rates and escalating costs. One contributing factor is the limited availability of mature cardiomyocytes (CMs) for accurate disease modeling and drug screening. Human induced pluripotent stem cell-derived CMs offer a promising source of CMs; however, their immature phenotype presents challenges in translational applications. This review focuses on the road to achieving mature CMs by summarizing the major differences between immature and mature CMs, discussing the importance of adult-like CMs for drug discovery, highlighting the limitations of current strategies, and exploring potential solutions using electro-mechano active polymer-based scaffolds based on conductive polymers. However, critical considerations such as the trade-off between 3D systems and nutrient exchange, biocompatibility, degradation, cell adhesion, longevity, and integration into wider systems must be carefully evaluated. Continued advancements in these areas will contribute to a better understanding of cardiac diseases, improved drug discovery, and the development of personalized treatment strategies for patients with cardiovascular disorders.


Assuntos
Miócitos Cardíacos , Polímeros , Humanos , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Polímeros/química , Células-Tronco Pluripotentes Induzidas/citologia , Animais , Alicerces Teciduais/química , Diferenciação Celular , Doenças Cardiovasculares/terapia , Engenharia Tecidual/métodos
14.
Front Cell Infect Microbiol ; 14: 1327299, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38343890

RESUMO

In this study, two distinct in vitro infection models of Aspergillus fumigatus, using murine macrophages (RAW264.7) and human lung epithelial cells (A549), were employed to identify the genes important for fungal adaptation during infection. Transcriptomic analyses of co-incubated A. fumigatus uncovered 140 fungal genes up-regulated in common between both models that, when compared with a previously published in vivo transcriptomic study, allowed the identification of 13 genes consistently up-regulated in all three infection conditions. Among them, the maiA gene, responsible for a critical step in the L-phenylalanine degradation pathway, was identified. Disruption of maiA resulted in a mutant strain unable to complete the Phe degradation pathway, leading to an excessive production of pyomelanin when this amino acid served as the sole carbon source. Moreover, the disruption mutant exhibited noticeable cell wall abnormalities, with reduced levels of ß-glucans within the cell wall but did not show lack of chitin or mannans. The maiA-1 mutant strain induced reduced inflammation in primary macrophages and displayed significantly lower virulence in a neutropenic mouse model of infection. This is the first study linking the A. fumigatus maiA gene to fungal cell wall homeostasis and virulence.


Assuntos
Aspergillus fumigatus , Proteínas Fúngicas , Animais , Humanos , Camundongos , Aspergillus fumigatus/metabolismo , Parede Celular/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Homeostase , Virulência/genética
15.
Med Sci Sports Exerc ; 56(7): 1337-1344, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38376997

RESUMO

PURPOSE: The objective of this study is to assess the influence of "super-shoes" on metabolic cost and joint mechanics in competitive female runners and to understand how foot strike pattern may influence the footwear effects. METHODS: Eighteen competitive female runners ran four 5-min bouts on a force instrumented treadmill at 12.9 km·h -1 in 1) Nike Vaporfly Next% 2™ (SUPER) and 2) Nike Pegasus 38™ (CON) in a randomized and mirrored order. RESULTS: Metabolic power was improved by 4.2% ( P < 0.001; d = 0.43) and metatarsophalangeal (MTP) negative work ( P < 0.001; d = 1.22), ankle negative work ( P = 0.001; d = 0.67), and ankle positive work ( P < 0.001; d = 0.97) were all smaller when running in SUPER compared with CON. There was no correlation between foot strike pattern and the between-shoe (CON to SUPER) percentage change for metabolic power ( r = 0.093, P = 0.715). CONCLUSIONS: Metabolic power improved by 4.2% in "super-shoes" (but only by ~3.2% if controlling for shoe mass differences) in this cohort of competitive female runners, which is a smaller improvement than previously observed in men. The reduced mechanical demand at the MTP and ankle in "super-shoes" are consistent with previous literature and may explain or contribute to the metabolic improvements observed in "super-shoes"; however, foot strike pattern was not a moderating factor for the metabolic improvements of "super-shoes." Future studies should directly compare the metabolic response among different types of "super-shoes" between men and women.


Assuntos
Metabolismo Energético , , Corrida , Sapatos , Humanos , Feminino , Corrida/fisiologia , Fenômenos Biomecânicos , Metabolismo Energético/fisiologia , Adulto , Pé/fisiologia , Adulto Jovem , Articulação do Tornozelo/fisiologia , Marcha/fisiologia , Consumo de Oxigênio/fisiologia
16.
Chemphyschem ; 25(4): e202400056, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38350712

RESUMO

The front cover artwork is provided by Prof. Jose Moran-Mirabal's group at McMaster University in Hamilton, Ontario, Canada. The image shows a 3D rendering and electron microscopy images of micro/nanostructured electrodes, fabricated through thermal shrinking of a shape memory polymer. Read the full text of the Review at 10.1002/cphc.202300535.

17.
Adv Respir Med ; 92(1): 58-65, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38247552

RESUMO

(1) Background: The breathing pattern is defined as the relationship between the tidal volume (VT) and breathing frequency (BF) for a given VE. The aim of this study was to evaluate whether inspiratory muscle training influenced the response of the breathing pattern during an incremental effort in amateur cyclists. (2) Methods: Eighteen amateur cyclists completed an incremental test to exhaustion, and a gas analysis on a cycle ergometer and spirometry were conducted. Cyclists were randomly assigned to two groups (IMTG = 9; CON = 9). The IMTG completed 6 weeks of inspiratory muscle training (IMT) using a PowerBreathe K3® device at 50% of the maximum inspiratory pressure (Pimax). The workload was adjusted weekly. The CON did not carry out any inspiratory training during the experimental period. After the 6-week intervention, the cyclists repeated the incremental exercise test, and the gas analysis and spirometry were conducted. The response of the breathing pattern was evaluated during the incremental exercise test. (3) Results: The Pimax increased in the IMTG (p < 0.05; d = 3.1; +19.62%). Variables related to the breathing pattern response showed no differences between groups after the intervention (EXPvsCON; p > 0.05). Likewise, no differences in breathing pattern were found in the IMTG after training (PREvsPOST; p > 0.05). (4) Conclusions: IMT improved the strength of inspiratory muscles and sport performance in amateur cyclists. These changes were not attributed to alterations in the response of the breathing pattern.


Assuntos
Exercício Físico , Modalidades de Fisioterapia , Humanos , Teste de Esforço , Músculos , Respiração
18.
Diabetes Care ; 47(2): 295-303, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38241499

RESUMO

BACKGROUND: The optimal dose or type of physical activity to control glycosylated hemoglobin (HbA1c) in people with diabetes remains unknown. Current guidelines do not include consideration of baseline HbA1c for activity prescription. PURPOSE: To examine the dose-response relationship between physical activity and HbA1c (%) in individuals with type 2 diabetes. DATA SOURCES: A systematic search was performed in Embase, MEDLINE, Scopus, CINAHL, SPORTDiscus, and Web of Science. STUDY SELECTION: We included trials that involved participants diagnosed with type 2 diabetes that included any type of physical activity as intervention. DATA EXTRACTION: Pre- and postintervention HbA1c data, population and interventions characteristics, and descriptive statistics were collected to calculate change scores for each study arm. DATA SYNTHESIS: We used Bayesian random-effects meta-analyses to summarize high-quality evidence from 126 studies (6,718 participants). The optimal physical activity dose was 1,100 MET min/week, resulting in HbA1c reductions, ranging from -1.02% to -0.66% in severe uncontrolled diabetes, from -0.64% to -0.49% in uncontrolled diabetes, from -0.47% to -0.40% in controlled diabetes, and from -0.38% to -0.24% in prediabetes. LIMITATIONS: The time required to achieve these HbA1c reductions could not be estimated due to the heterogeneity between interventions' duration and protocols and the interpersonal variability of this outcome. CONCLUSIONS: The result of this meta-analysis provide key information about the optimal weekly dose of physical activity for people with diabetes with consideration of baseline HbA1c level, and the effectiveness of different types of active interventions. These results enable clinicians to prescribe tailored physical activity programs for this population.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Hemoglobinas Glicadas , Controle Glicêmico , Teorema de Bayes , Exercício Físico
19.
Chemphyschem ; 25(4): e202300535, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38060839

RESUMO

Since their discovery in the 1940s, shape memory polymers (SMPs) have been used in a broad spectrum of applications for research and industry.[1] SMPs can adopt a temporary shape and promptly return to their original form when submitted to an external stimulus. They have proven useful in fields such as wearable and stretchable electronics,[2] biomedicine,[3] and aerospace..[4] These materials are attractive and unique due to their ability to "remember" a shape after being submitted to elastic deformation. By combining the properties of SMPs with the advantages of electrochemistry, opportunities have emerged to develop structured sensing devices through simple and inexpensive fabrication approaches. The use of electrochemistry for signal transduction provides several advantages, including the translation into inexpensive sensing devices that are relatively easy to miniaturize, extremely low concentration requirements for detection, rapid sensing, and multiplexed detection. Thus, electrochemistry has been used in biosensing,[5] pollutant detection,[6] and pharmacological[7] applications, among others. To date, there is no review that summarizes the literature addressing the use of SMPs in the fabrication of structured electrodes for electrochemical sensing. This review aims to fill this gap by compiling the research that has been done on this topic over the last decade.

20.
Int Immunol ; 36(3): 111-128, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38066638

RESUMO

Nurr1 is a member of the orphan nuclear receptor family NR4A (nuclear receptor subfamily 4 group A) that modulates inflammation in several cell lineages, both positively and negatively. Macrophages are key regulators of inflammatory responses, yet information about the role of Nurr1 in human macrophages is scarce. Here we examined Nurr1 expression and activity in steady state and activated human macrophages. Pro- and anti-inflammatory macrophages were generated in vitro by culture of blood monocytes with granulocyte/macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF), respectively. Nurr1 expression was predominant in macrophages with the pro-inflammatory phenotype. Nurr1 activation with the agonists 1,1-bis(3'-indolyl)-1-(p-chlorophenyl) methane (C-DIM12) or isoxazolo-pyridinone 7e (IP7e) did not globally modify the polarization status of pro-inflammatory macrophages, but they decreased their production of TNF, IL-1ß, IL-6, IL-8, IL-12 p40, CCL2, IFN-ß, and reactive oxygen species, with variable potencies. Conversely, Nurr1 deficient macrophages increased the expression of transcripts encoding inflammatory mediators, particularly that of IL6, IFNB1, and CCL2. Mechanistically, endogenous Nurr1 interacted with NF-κB p65 in basal conditions and upon lipopolysaccharide (LPS)-mediated activation. C-DIM12 stabilized those complexes in cells exposed to LPS and concurrently decreased NF-κB transcriptional activity and p65 nuclear translocation. Expression of high levels of Nurr1 was associated with a subset of dermal macrophages that display enhanced levels of TNF and lower expression of the anti-inflammatory marker CD163L1 in skin lesions from patients with bullous pemphigoid (BP), a chronic inflammatory autoimmune blistering disorder. These results suggest that Nurr1 expression is linked with the pro-inflammatory phenotype of human macrophages, both in vivo and in vitro, where it may constitute a brake to attenuate the synthesis of inflammatory mediators.


Assuntos
Fator Estimulador de Colônias de Macrófagos , NF-kappa B , Humanos , NF-kappa B/metabolismo , Fator Estimulador de Colônias de Macrófagos/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Anti-Inflamatórios/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA