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1.
Int J Mol Sci ; 22(9)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34066927

RESUMO

Anandamide (AEA) is one of the best characterized members of the endocannabinoid family and its involvement in many pathophysiological processes has been well documented in vertebrates and invertebrates. Here, we report the biochemical and functional characterization of key elements of the endocannabinoid system in hemocytes isolated from the Mediterranean mussel Mytilus galloprovincialis. We also show the effects of exogenous AEA, as well as of capsaicin, on the cell ability to migrate and to activate the respiratory burst, upon in vitro stimulation of phagocytosis. Interestingly, our findings show that both AEA and capsaicin suppress the hemocyte response and that the use of selective antagonists of CB2 and TRPV1 receptors revert their inhibitory effects. Overall, present data support previous evidence on the presence of endocannabinoid signaling in mollusks and advance our knowledge about the evolutionary origins of this endogenous system and its role in the innate response of mollusks.


Assuntos
Endocanabinoides/metabolismo , Mytilus/imunologia , Sequência de Aminoácidos , Animais , Ácidos Araquidônicos/farmacologia , Capsaicina/farmacologia , Endocanabinoides/farmacologia , Hemócitos/efeitos dos fármacos , Hemócitos/metabolismo , Mytilus/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Filogenia , Alcamidas Poli-Insaturadas/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Canabinoides/química , Receptores de Canabinoides/genética , Receptores de Canabinoides/metabolismo , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismo
2.
Front Immunol ; 12: 618569, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34046029

RESUMO

Glucocorticoids are effective drugs for treating immune-related diseases, but prolonged therapy is associated with an increased risk of various infectious diseases, including tuberculosis. In this study, we have used a larval zebrafish model for tuberculosis, based on Mycobacterium marinum (Mm) infection, to study the effect of glucocorticoids. Our results show that the synthetic glucocorticoid beclomethasone increases the bacterial burden and the dissemination of a systemic Mm infection. The exacerbated Mm infection was associated with a decreased phagocytic activity of macrophages, higher percentages of extracellular bacteria, and a reduced rate of infected cell death, whereas the bactericidal capacity of the macrophages was not affected. The inhibited phagocytic capacity of macrophages was associated with suppression of the transcription of genes involved in phagocytosis in these cells. The decreased bacterial phagocytosis by macrophages was not specific for Mm, since it was also observed upon infection with Salmonella Typhimurium. In conclusion, our results show that glucocorticoids inhibit the phagocytic activity of macrophages, which may increase the severity of bacterial infections like tuberculosis.


Assuntos
Glucocorticoides/efeitos adversos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Infecções por Mycobacterium não Tuberculosas/imunologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium marinum/efeitos dos fármacos , Mycobacterium marinum/imunologia , Fagocitose/efeitos dos fármacos , Fagocitose/imunologia , Animais , Carga Bacteriana , Beclometasona/metabolismo , Imunofenotipagem , Imunossupressores/efeitos adversos , Ativação de Macrófagos/efeitos dos fármacos , Ativação de Macrófagos/genética , Ativação de Macrófagos/imunologia , Macrófagos/metabolismo , Infecções por Mycobacterium não Tuberculosas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores de Glucocorticoides/metabolismo , Peixe-Zebra
3.
Int J Biol Macromol ; 183: 972-981, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-33965492

RESUMO

Polysaccharide is one of the necessary macromolecules in life activities, and it is also a very promising natural product for tumor prevention and treatment. In this study, two homogeneous polysaccharides (APS-4I and APS-4II) were isolated from Angelica sinensis (Oliv.) Diels. APS-4I was a linear glucan with molecular weight of 16.1 kDa, which was composed of 88.4% α-1,6-Glcp, 4.1% α-1,2-Glcp, 3.9% α-1,3-Glcp, and 2.8% α-T-Glcp. APS-4II was a novel polysaccharide with molecular weight of 11.1 kDa, which consisted of 55.4% α-1,6-Glcp, 10.4% α-1,3,5-Araf, 8.7% α-T-Araf, 9.2% α-1,5-Araf, 4.0% α-1,3-Araf, 3.6% α-1,4-Galp, and 9.1% ß-1,3-Galp. NMR results demonstrated that APS-4II has a backbone composed of →6)-α-Glcp-(1 → 6)-α-Glcp-(1 → 5)-α-Araf-. (1 → 5)-α-Araf-(1 → 3,5)-α-Araf-(1 → 3)-ß-Galp-(1 → 3)-ß-Galp-(1 → 4)-α-Galp-(1 → 3)-α-Araf-(1 → 3,5)-α-Araf-(1→. Both APS-4I and APS-4II inhibited the tumor growth of B16-bearing mice, and the suppressive effect of APS-4II reached 64.7 ± 7.3%. Meanwhile, there were higher lymphocyte numbers and the levels of IL-2, IFN-γ, and TNF-α in peripheral blood of APS-4II-treated mice than those in APS-4I-treated mice. Furthermore, APS-4II showed a higher inhibitory effect on the proliferation of B16 cells and stronger promoting effects on the proliferation of splenocytes, the phagocytosis of peritoneal macrophages, and the cytotoxicity of NK cells. These results demonstrated that APS-4II could be a promising therapeutic agent for melanoma.


Assuntos
Angelica sinensis/química , Polissacarídeos/química , Polissacarídeos/uso terapêutico , Animais , Proliferação de Células/efeitos dos fármacos , Interferon gama/sangue , Interleucina-2/sangue , Melanoma/sangue , Melanoma/tratamento farmacológico , Camundongos , Peso Molecular , Fagocitose/efeitos dos fármacos , Polissacarídeos/farmacologia , Fator de Necrose Tumoral alfa/sangue
4.
Nat Commun ; 12(1): 3142, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34035264

RESUMO

Transthyretin amyloid (ATTR) cardiomyopathy is a debilitating disease leading to heart failure and death. It is characterized by the deposition of extracellular ATTR fibrils in the myocardium. Reducing myocardial ATTR load is a therapeutic goal anticipated to translate into restored cardiac function and improved patient survival. For this purpose, we developed the selective anti-ATTR antibody NI301A, a recombinant human monoclonal immunoglobulin G1. NI301A was cloned following comprehensive analyses of memory B cell repertoires derived from healthy elderly subjects. NI301A binds selectively with high affinity to the disease-associated ATTR aggregates of either wild-type or variant ATTR related to sporadic or hereditary disease, respectively. It does not bind physiological transthyretin. NI301A removes ATTR deposits ex vivo from patient-derived myocardium by macrophages, as well as in vivo from mice grafted with patient-derived ATTR fibrils in a dose- and time-dependent fashion. The biological activity of ATTR removal involves antibody-mediated activation of phagocytic immune cells including macrophages. These data support the evaluation of safety and tolerability of NI301A in an ongoing phase 1 clinical trial in patients with ATTR cardiomyopathy.


Assuntos
Neuropatias Amiloides Familiares/tratamento farmacológico , Anticorpos Monoclonais/farmacologia , Cardiomiopatias/tratamento farmacológico , Macrófagos/imunologia , Pré-Albumina/antagonistas & inibidores , Idoso de 80 Anos ou mais , Neuropatias Amiloides Familiares/genética , Neuropatias Amiloides Familiares/patologia , Animais , Anticorpos Monoclonais/uso terapêutico , Cardiomiopatias/patologia , Ensaios Clínicos Fase I como Assunto , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Mutação , Miocárdio/patologia , Fagocitose/efeitos dos fármacos , Fagocitose/imunologia , Pré-Albumina/genética , Pré-Albumina/metabolismo , Agregados Proteicos/efeitos dos fármacos , Agregados Proteicos/imunologia , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Transplante Heterólogo
5.
Int J Biol Macromol ; 182: 743-749, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33831450

RESUMO

The development of high-end targeted drugs and vaccines against modern pandemic infections, such as COVID-19, can take a too long time that lets the epidemic spin up and harms society. However, the countermeasures must be applied against the infection in this period until the targeted drugs became available. In this regard, the non-specific, broad-spectrum anti-viral means could be considered as a compromise allowing overcoming the period of trial. One way to enhance the ability to resist the infection is to activate the nonspecific immunity using a suitable driving-up agent, such as plant polysaccharides, particularly our drug Panavir isolated from the potato shoots. Earlier, we have shown the noticeable anti-viral and anti-bacterial activity of Panavir. Here we demonstrate the pro-inflammation activity of Panavir, which four-to-eight times intensified the ATP and MIF secretion by HL-60 cells. This effect was mediated by the active phagocytosis of the Panavir particles by the cells. We hypothesized the physiological basis of the Panavir proinflammatory activity is mediated by the indol-containing compounds (auxins) present in Panavir and acting as a plant analog of serotonin.


Assuntos
Antivirais , COVID-19/tratamento farmacológico , Portadores de Fármacos , Nanopartículas , Plantas/química , Polissacarídeos , Probucol , Adolescente , Adulto , Antivirais/química , Antivirais/farmacocinética , Antivirais/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Células HL-60 , Humanos , Masculino , Nanopartículas/química , Nanopartículas/uso terapêutico , Fagocitose/efeitos dos fármacos , Polissacarídeos/química , Polissacarídeos/farmacologia , Probucol/química , Probucol/farmacocinética , Probucol/farmacologia
6.
Int J Biol Macromol ; 182: 207-216, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33831453

RESUMO

Arca subcrenata Lischke is a seafood with high nutritional value. In this study, we purified and characterized a novel water-soluble polysaccharide (ASPG-2) from Arca subcrenata with significant immunoregulatory effects and no apparent cell toxicity. ASPG-2 is a class of mixed-linkage α,ß-d-glucan backbones with α-linked side chains with a molecular weight of 4.39 × 105 Da. Its structure was characterized as a repeating unit consisting of (1 → 3)-ß-d-Glcp, (1 → 4)-α-d-Glcp, (1 → 4,6)-α-d-Glcp and (1 → 6)-α-d-Glcp. Using mouse RAW264.7 macrophages, we demonstrated that ASPG-2 exerted marked immunoregulatory effects by promoting the secretion of NO and increasing the phagocytosis of RAW264.7 cells in vitro. Moreover, flow cytometry analysis of the expression of the cell surface molecule CD86 revealed that ASPG-2 could polarize RAW264.7 cells into the M1 type. The immunomodulatory mechanism of ASPG-2 in macrophages was associated with the activation of the TLR4-MAPK/Akt-NF-κB signalling pathways. These results indicated that ASPG-2 might be researched and developed as a potential immunomodulatory agent or health product from marine organisms.


Assuntos
Arcidae/química , Glucanos/isolamento & purificação , Fagocitose/efeitos dos fármacos , Alimentos Marinhos/análise , Transdução de Sinais , Animais , Sequência de Carboidratos , Glucanos/análise , Glucanos/farmacologia , Imunomodulação , Camundongos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Peso Molecular , NF-kappa B/metabolismo , Células RAW 264.7
7.
Int J Biol Macromol ; 183: 90-100, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-33872613

RESUMO

A water-soluble polysaccharide identified here as ADP80-2 was acquired from Angelica dahurica. ADP80-2 was a gluco-arabinan composed of arabinose and a trace of glucose with a molecular weight of 9950 g/mol. The backbone of ADP80-2 comprised →5)-α-L-Araf-(1→, →3, 5)-α-L-Araf-(1→, →6)-α-D-Glcp-(1→, with a terminal branch α-L-Araf-(1 → residue. In terms of immunoregulatory activity, ADP80-2 can significantly promote the phagocytosis, the production of nitric oxide (NO), and the secretion of cytokines (IL-6, IL-1ß, and TNF-α) of macrophage. In addition to the cellular immunomodulatory activities, the chemokines related to immunoregulation were significantly increased in the zebrafish model after treated with ADP80-2. These biological results indicated that ADP80-2 with immunomodulatory effects was expected to be useful for the development of new immunomodulatory agents. Simultaneously, the discovery of ADP80-2 further revealed the chemical composition of A. dahurica used as a traditional Chinese medicine and spice.


Assuntos
Angelica , Fatores Imunológicos/farmacologia , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Angelica/química , Animais , Configuração de Carboidratos , Citocinas/metabolismo , Fatores Imunológicos/isolamento & purificação , Mediadores da Inflamação/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Fagocitose/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Polissacarídeos/isolamento & purificação , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Peixe-Zebra/embriologia , Proteínas de Peixe-Zebra/metabolismo
8.
Int J Biol Macromol ; 183: 145-157, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-33878360

RESUMO

Two novel glucans named MIPB50-W and MIPB50-S-1 were obtained from edible Morchella importuna with molecular weights (Mw) of 939.2 kDa and 444.5 kDa, respectively. MIPB50-W has a backbone of α-(1 → 4)-d-glucan, which was substituted at O-6 position by α-d-Glcp-(1→. Moreover, MIPB50-S-1 has a backbone of α-(1 → 4)-d-glucan, which was substituted at O-6 position by α-d-Glcp-(1 → 6)-α-d-Glcp-(1→. This is the first report about glucan found in Morchella mushrooms. Furthermore, MIPB50-W and MIPB50-S-1 strengthened the phagocytosis function and the promoted secretion of interleukins (IL)-6/tumor necrosis factor-alpha (TNF-α) and nitric oxide (NO), which induced the activation of Toll-like receptor 2 (TLR2), TLR4 as well as mitogen activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways. Interestingly, MIPB50-S-1 performed the better immunomodulatory activity than that of MIPB50-W in almost all tests. Therefore, MIPB50-W and MIPB50-S-1 are potential immune-enhancing components of functional foods.


Assuntos
Ascomicetos/metabolismo , Carpóforos/metabolismo , Glucanos/farmacologia , Fatores Imunológicos/farmacologia , Macrófagos/efeitos dos fármacos , Animais , Glucanos/química , Glucanos/isolamento & purificação , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Interleucina-6/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Estrutura Molecular , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Fagocitose/efeitos dos fármacos , Células RAW 264.7 , Transdução de Sinais , Relação Estrutura-Atividade , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
9.
Int J Biol Macromol ; 183: 79-89, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-33901556

RESUMO

Agaricus bitorquis (QuéL.) Sacc. Chaidam is a valuable edible fungus in Qinghai-Tibet plateau and ABSP is a novel intracellular polysaccharide from its mycelia. GC and NMR analysis determined ABSP is galactoglucomannan-like polysaccharide that may have immunomodulatory effect. This study used RAW264.7 as model cell to determine immunomodulatory effect of ABSP. After ABSP treatment, viability and phagocytic ability promoted, and NO, ROS, TNF-α levels also raised which proved ABSP had immune regulation to RAW264.7. WB and qRT-PCR determined the key proteins and genes expression of TLR4, MyD88, TRAF-6 and NF-κB significantly increased while protein and gene expression of TRAM had no significant increase. Also, TNF-α level extremely decreased by adding inhibitors of TLR4 and MyD88 which confirmed ABSP could immunologically regulate RAW264.7 byTLR4-MyD88 dependent pathway. This study would provide theoretical basis for further study on ABSP and be helpful for development of beneficial functionally foods and exploitation of this resource.


Assuntos
Agaricus/química , Polissacarídeos Fúngicos/farmacologia , Fatores Imunológicos/farmacologia , Macrófagos/efeitos dos fármacos , Fator 88 de Diferenciação Mieloide/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Polissacarídeos Fúngicos/isolamento & purificação , Fatores Imunológicos/isolamento & purificação , Mediadores da Inflamação/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Fagocitose/efeitos dos fármacos , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
10.
Nutrients ; 13(3)2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33809720

RESUMO

The prevalence of acute respiratory infections and their impact on quality of life underlies the need for efficacious solutions that are safe, sustainable and economically viable. Polysaccharides in several (traditional) plant extracts have been shown to be immunostimulatory, and some studies suggest beneficial effects against respiratory infections. The aim of this study was to (i) identify the active polysaccharide constituents from affordable and renewable crops (bell pepper and carrot) using activity-guided fractionation, (ii) evaluate in vitro effects on innate immune responses (phagocytosis and cytokine secretion), microbiota modulation and production of short chain fatty acids, followed by (iii) the evaluation of effects of a bell pepper extract enriched for the active component in a human proof of concept study. We identified rhamnogalacturonan-I (RG-I) as the nutricophore responsible for the immunostimulatory activity with substantial structural and functional equivalence between bell pepper (bp) and carrot (c). The in vitro studies showed that bpRG-I and cRG-I comprise similar immune- and microbiota modulatory potential and the human study demonstrated that bpRG-I was well tolerated and enhanced innate immune responsiveness in vivo. This is an important step towards testing the efficacy of RG-I from bpRG-I or cRG-I in an infection trial in humans.


Assuntos
Capsicum/química , Daucus carota/química , Fatores Imunológicos/farmacologia , Pectinas/farmacologia , Fitoterapia/métodos , Extratos Vegetais/farmacologia , Adulto , Idoso , Citocinas/metabolismo , Método Duplo-Cego , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Fatores Imunológicos/isolamento & purificação , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/fisiologia , Masculino , Pessoa de Meia-Idade , Pectinas/isolamento & purificação , Fagocitose/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Estudo de Prova de Conceito , Adulto Jovem
11.
Int J Mol Sci ; 22(7)2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805517

RESUMO

Corylin, a flavonoid isolated from the fruit of Psoralea corylifolia, has an osteogenic effect on osteoblasts in vitro and bone micromass ex vivo. However, the effect and mechanism of corylin in regulating osteoclastogenesis remain unknown. By using murine bone marrow macrophages as the osteoclast precursor, corylin was found to inhibit the receptor activator of nuclear factor (NF) κB ligand (RANKL)-induced osteoclast differentiation via down-regulating osteoclastic marker genes. In parallel, F-actin formation and osteoclast migration were diminished in corylin-treated cultured osteoclasts, and subsequently the expressions of osteoclastic proteins were suppressed: the suppression of protein expression was further illustrated by transcriptomic analysis. Furthermore, corylin inhibited the nuclear translocation of p65, giving rise to a restraint in osteoclastic differentiation through the attenuation of transcription factors nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nuclear factor of activated T cells c1 (NFATc1). There was no obvious change in apoptosis when the RANKL-induce osteoclasts were cultured in the presence of corylin. The finding supports the potential development of corylin as an osteoclast inhibitor against osteoporosis.


Assuntos
Flavonoides/farmacologia , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Feminino , Perfilação da Expressão Gênica , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Osteoclastos/fisiologia , Osteogênese/fisiologia , Fagocitose/efeitos dos fármacos , Ligante RANK/genética , Células RAW 264.7
12.
Vet Surg ; 50(4): 858-871, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33797775

RESUMO

OBJECTIVE: To evaluate effects of Toll-like and nucleotide-binding oligomerization domain (NOD)-like receptor (TLR, NLR) ligand stimulation of equine mesenchymal stromal cells (MSCs) on antibacterial and immunomodulatory properties in vitro. STUDY DESIGN: Controlled laboratory study. SAMPLE POPULATION: Equine bone-marrow-derived MSCs (three horses). METHODS: MSCs were stimulated with TLR (polyinosinic:polycytidylic acid [pIC] and lipopolysaccharide [LPS]) and NLR agonists (γ-d-Glu-mDAP [IE-DAP]) for 2 h, and plated at 1 × 105 cells/well 24 h. MSC-conditioned media (MSC-CM) were collected and assessed for antimicrobial peptide cathelicidin/LL-37 production, bactericidal action against multidrug-resistant planktonic and biofilm Staphylococcus aureus and neutrophil phagocytosis. Bacterial growth was measured by plating bacteria and counting viable colonies, reading culture absorbance, and live-dead staining with confocal microscopy imaging. Following initial comparison of activating stimuli, TLR3-agonist pIC protocols (cell density during activation and plating, culture time, %serum) were further optimized for bactericidal activity and secretion of interleukin-8 (IL-8), monocyte-chemoattractant-protein (MCP-1), and cathelicidin/LL37. RESULTS: MSCs stimulation with pIC (p = .004) and IE-DAP (p = .03) promoted increased bactericidal activity, evidenced by reduced viable planktonic colony counts. PIC stimulation (2 × 106 cells/ml, 2 h, 10 µg/ml) further suppressed biofilm formation (p = .001), enhanced neutrophil bacterial phagocytosis (p = .009), increased MCP-1 secretion (p < .0001), and enhanced cathelicidin/LL-37 production, which was apparent when serum concentration in media was reduced to 1% (p = .01) and 2.5% (p = .05). CONCLUSION: TLR-3 pIC MSCs activation was most effective to enhance antibacterial and cytokine responses, which were affected by serum reduction. CLINICAL SIGNIFICANCE: In vitro TLR-3 activation of equine MSCs tested here may be a strategy to improve antibacterial properties of MSCs to treat antibiotic-resistant infections.


Assuntos
Peptídeos Catiônicos Antimicrobianos/biossíntese , Cavalos/imunologia , Imunomodulação/genética , Células-Tronco Mesenquimais/imunologia , Fagocitose/efeitos dos fármacos , Staphylococcus aureus/fisiologia , Receptores Toll-Like/metabolismo , Animais , Biofilmes , Citocinas/biossíntese , Farmacorresistência Bacteriana Múltipla/imunologia , Neutrófilos/efeitos dos fármacos
13.
Int J Biol Macromol ; 180: 129-142, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33676979

RESUMO

The current experiments were designed to explore the structural features and immunopotentiation activity of two homogeneous polysaccharides PCSPA and PCSPB prepared from Crocus sativus petals using DEAE-Sephadex A-50 and Sephadex G200 column chromatography. The structures of PCSPA and PCSPB were systematically characterized using extensive chemical and spectroscopic methods including colorimetry, HPGPC-RID, GC-MS, Smith degradations, methylation, solvolytic desulfation, UV, FT-IR, NMR, SEM, and AFM. The average molecular weights of PCSPA and PCSPB were 1.98 × 106 and 2.53 × 106 Da, respectively. PCSPA consisted of Gal, Rha, Ara, and Xyl in the molar ratio of 16:5:7:3, while PCSPB were composed of Gal, Glc, Man, Rha, Ara, and Xyl with molar ratio of 16:2:7:19:15:16. Both polysaccharides contained sulfonic and acetyl groups. PCSPA and PCSPB significantly activated RAW264.7 cells by enhancing the phagocytic activity, up-regulating the expression of surface molecules, promoting the production and mRNA expression of cytokines and chemokines via MAPK and NF-κB pathway.


Assuntos
Crocus/química , Flores/química , Ativação de Macrófagos/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polissacarídeos/química , Polissacarídeos/farmacologia , Animais , Configuração de Carboidratos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quimiocinas/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Ativação de Macrófagos/imunologia , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Peso Molecular , NF-kappa B/metabolismo , Fagocitose/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Polissacarídeos/isolamento & purificação , Células RAW 264.7
14.
Mar Drugs ; 19(3)2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33670856

RESUMO

Exopolysaccharides, or extracellular polysaccharides (EPS, sPS), represent a valuable metabolite compound synthesized from red microalgae. It is a non-toxic natural agent and can be applied as an immunostimulant. The toxicity test of exopolysaccharides from Porphyridium has been done in vivo using zebrafish (Danio rerio) embryonic model, or the ZET (zebrafish embryotoxicity test). The administration of extracellular polysaccharides or exopolysaccharides (EPS) from microalgae Porphyridium cruentum (synonym: P. purpureum) to shrimps Litopenaeus vannamei was investigated to determine the effect of this immunostimulant on their non-specific immune response and to test if this compound can be used as a protective agent for shrimps in relation to Vibrio infection. For immune response, exopolysaccharides were given to shrimps via the immersion method on day 1 and booster on day 8. Shrimp hemocytes were taken on day 1 (EPS administration), day 7 (no treatment), day 8 (EPS booster) and day 9 (Vibrio infection) and tested for their immune response on each treatment. The result shows that the EPS is not toxic, as represented by the normal embryonic development and the mortality data. In the Pacific white shrimps, an increase in the values of all immune parameters was shown, in line with the increasing EPS concentration, except for the differential hemocyte count (DHC). In detail, an increase was noted in total hemocytes (THC) value, phagocytotic activity (PA) and respiratory burst (RB) in line with the EPS concentration increase. These results and other previous studies indicate that EPS from Porphyridium is safe, enhances immune parameters in shrimp rapidly, and has the ability to act as an immunostimulant or an immunomodulator. It is a good modulator for the non-specific immune cells of Pacific white shrimps, and it can be used as a preventive agent against vibriosis.


Assuntos
Fatores Imunológicos/farmacologia , Polissacarídeos/farmacologia , Porphyridium/metabolismo , Vibrioses/prevenção & controle , Animais , Modelos Animais de Doenças , Hemócitos/citologia , Hemócitos/efeitos dos fármacos , Fatores Imunológicos/isolamento & purificação , Fatores Imunológicos/toxicidade , Penaeidae , Fagocitose/efeitos dos fármacos , Polissacarídeos/isolamento & purificação , Polissacarídeos/toxicidade , Explosão Respiratória/efeitos dos fármacos , Fatores de Tempo , Peixe-Zebra
15.
Nat Commun ; 12(1): 1704, 2021 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731716

RESUMO

GPR37 was discovered more than two decades ago, but its biological functions remain poorly understood. Here we report a protective role of GPR37 in multiple models of infection and sepsis. Mice lacking Gpr37 exhibited increased death and/or hypothermia following challenge by lipopolysaccharide (LPS), Listeria bacteria, and the mouse malaria parasite Plasmodium berghei. Sepsis induced by LPS and Listeria in wild-type mice is protected by artesunate (ARU) and neuroprotectin D1 (NPD1), but the protective actions of these agents are lost in Gpr37-/- mice. Notably, we found that ARU binds to GPR37 in macrophages and promotes phagocytosis and clearance of pathogens. Moreover, ablation of macrophages potentiated infection, sepsis, and their sequelae, whereas adoptive transfer of NPD1- or ARU-primed macrophages reduced infection, sepsis, and pain-like behaviors. Our findings reveal physiological actions of ARU in host cells by activating macrophages and suggest that GPR37 agonists may help to treat sepsis, bacterial infections, and malaria.


Assuntos
Macrófagos/metabolismo , Dor/prevenção & controle , Receptores Acoplados a Proteínas G/metabolismo , Sepse/prevenção & controle , Transferência Adotiva , Animais , Artesunato/metabolismo , Artesunato/farmacologia , Artesunato/uso terapêutico , Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/metabolismo , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Docosa-Hexaenoicos/uso terapêutico , Lipopolissacarídeos/toxicidade , Listeria monocytogenes/patogenicidade , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Macrófagos/transplante , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Simulação de Acoplamento Molecular , Dor/imunologia , Dor/mortalidade , Fagocitose/efeitos dos fármacos , Plasmodium berghei/patogenicidade , Receptores Acoplados a Proteínas G/deficiência , Sepse/imunologia , Sepse/mortalidade , Sepse/terapia
16.
Int J Mol Sci ; 22(4)2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33673336

RESUMO

The mammalian immune system senses foreign antigens by mechanisms that involve the interplay of various kinds of immune cells, culminating in inflammation resolution and tissue clearance. The ability of the immune cells to communicate (via chemokines) and to shift shape for migration, phagocytosis or antigen uptake is mainly supported by critical proteins such as aquaporins (AQPs) that regulate water fluid homeostasis and volume changes. AQPs are protein channels that facilitate water and small uncharged molecules' (such as glycerol or hydrogen peroxide) diffusion through membranes. A number of AQP isoforms were found upregulated in inflammatory conditions and are considered essential for the migration and survival of immune cells. The present review updates information on AQPs' involvement in immunity and inflammatory processes, highlighting their role as crucial players and promising targets for drug discovery.


Assuntos
Aquaporinas/imunologia , Movimento Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Desenvolvimento de Medicamentos , Fagocitose/efeitos dos fármacos , Animais , Transporte Biológico/efeitos dos fármacos , Transporte Biológico/imunologia , Movimento Celular/imunologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/imunologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/patologia
17.
Carbohydr Polym ; 260: 117796, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33712144

RESUMO

The polysaccharide (DRP) was gained from dandelion roots by ultrasonic-assisted enzymatic extraction (UAEE) followed by two-step column purification. Then selenylation of DRP has been accomplished by HNO3-Na2SeO3 method. sDRP-1 and sDRP-2 with the selenium content of 170 ± 1.13 and 710 ± 4.00 µg/g were prepared for further structural characterization and bioactivity determination. DRP, sDRP-1, and sDRP-2 were composed of the same monosaccharides in different molar ratios, and the molecular weights of DRP, sDRP-1 and sDRP-2 were 8700, 7900, and 5600 Da, respectively. Fourier transform infrared (FT-IR) spectra confirmed that DRP, sDRP-1, and sDRP-2 possessed similar functional groups. The results of Congo red test, X-ray diffraction (XRD) and scanning electron microscopy (SEM) showed that DRP, sDRP-1, and sDRP-2 had no three helix structure, did not form single crystal, and all belonged to amorphous morphology. sDRP-1 and sDRP-2 possessed greater antioxidant activities in vitro than the native polysaccharide DRP. At the same time, the selenized polysaccharides showed better immunomodulatory ability and could be used as new-type immunoenhancer. The present conclusions provided theoretical basis for the new application of dandelion polysaccharides and the development of dandelion resources.


Assuntos
Antioxidantes/química , Polissacarídeos/química , Selênio/química , Taraxacum/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Fatores Imunológicos/química , Fatores Imunológicos/metabolismo , Fatores Imunológicos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Peso Molecular , Fagocitose/efeitos dos fármacos , Raízes de Plantas/metabolismo , Polissacarídeos/metabolismo , Polissacarídeos/farmacologia , Células RAW 264.7
18.
Med Sci Monit ; 27: e929004, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33684094

RESUMO

BACKGROUND Selenium and peroxynitrite are known to support the growth and activity of immune cells, including T cells, B cells and macrophages. However, the role of these factors in the immune function of human immature dendritic cells (imDCs) is not clear. MATERIAL AND METHODS Monocytes from a mixture of blood samples were isolated using Ficoll density gradient centrifugation and purified with immunomagnetic beads before being induced into imDCs. Cells then either received no treatment (control group), or treatment with sodium selenite (Na2SeO3, Se), 3-morpholinosydnonimine (SIN1, which decomposes into peroxynitrite), or Se+SIN1. Cell viability, migration, and antiphagocytic abilities, oxidative stress, and protein expression of extracellular signal-regulated kinases (ERK) and MMP2 were assessed using a CCK8 assay, cell counter and flow cytometry, microplate spectrophotometer, and Western blot analysis, respectively. RESULTS Viability of imDCs was unaffected by 0.1 µmol/L of Na2SeO3, although 1 mmol/L of SIN1 decreased it significantly (P<0.05). Chemotactic migration and antiphagocytic abilities were inhibited and enhanced, respectively, by treatment with Na2SeO3 and SIN1 (P<0.05). Activities of superoxide dismutase and glutathione peroxidase were increased by Na2SeO3 and Se+SIN1 (P<0.001). Glutathione content decreased with exposure to Na2SeO3 and SIN1 (P<0.05), but increased after treatment with Se+SIN1 (P<0.05). Levels of reactive oxygen species only increased with SIN1 treatment (P<0.05). Treatment with Na2SeO3, SIN1 and Se+SIN1 increased ERK phosphorylation and decreased MMP2 protein expression (P<0.05). CONCLUSIONS Selenium and peroxynitrite can influence immune function in imDCs by regulating levels of reactive oxygen species or glutathione to activate ERK and promote antigen phagocytosis, as well as by decreasing MMP2 expression to inhibit chemotactic migration.


Assuntos
Células Dendríticas/efeitos dos fármacos , Ácido Peroxinitroso/farmacologia , Selênio/farmacologia , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Dendríticas/metabolismo , Glutationa Peroxidase/metabolismo , Humanos , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ácido Peroxinitroso/imunologia , Fagocitose/efeitos dos fármacos , Fosforilação , Espécies Reativas de Oxigênio/metabolismo , Selênio/imunologia , Superóxido Dismutase/metabolismo
19.
Int Immunopharmacol ; 95: 107502, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33690000

RESUMO

BACKGROUND: Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease with a low platelet count. CD44 is a pivotal component involved in phagocytosis and inflammation, and monoclonal antibodies (mAbs) against CD44 have been shown to be beneficial in several autoimmune diseases. In the present study, we investigated the correlation between CD44 levels and disease severity in patients with ITP and explored the immunomodulatory mechanisms of the antihuman CD44 mAb BJ18 on platelet phagocytosis mediated by monocytes/macrophages. METHODS: Plasma was collected from 45 participants to measure the circulating concentration of CD44 using ELISA. Peripheral blood mononuclear cells from patients and controls were isolated and induced to differentiate into monocytes/macrophages utilizing cytokines and drugs. CD44 expression on circulating cells and the effects of BJ18 on platelet phagocytosis, Fcɣ receptor (FcɣR) expression and M1/M2 polarization of macrophages were evaluated using flow cytometry and qPCR. RESULTS: CD44 levels of both the soluble form found in plasma and the form expressed on the surface of circulating monocytes/macrophages were significantly elevated in ITP patients. Linear correlations were verified between the CD44 levels and major clinical characteristics. In an in vitro study, BJ18 successfully inhibited platelet phagocytosis by monocytes/macrophages obtained from ITP patients. Further studies indicated that BJ18 corrected abnormal FcγR expression on monocytes/macrophages. Moreover, the polarization of proinflammatory M1 macrophages could also be regulated by BJ18. CONCLUSIONS: Our data indicated that the CD44 level has potential predictive value for disease severity and that the antihuman CD44 mAb BJ18 may be a promising therapy for ITP patients.


Assuntos
Anticorpos Monoclonais/farmacologia , Plaquetas , Receptores de Hialuronatos/sangue , Fatores Imunológicos/farmacologia , Macrófagos/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Púrpura Trombocitopênica Idiopática/imunologia , Receptores de IgG/imunologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Receptores de Hialuronatos/imunologia , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Fagocitose/efeitos dos fármacos , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/genética , Receptores de IgG/genética , Adulto Jovem
20.
Int Immunopharmacol ; 94: 107445, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33592405

RESUMO

Studies have demonstrated that the modification of selenylation can improve the activity of polysaccharides. Lilium davidii var. unicolor Salisb (known as "lily bulb") is the dried succulent bulb of the genus Lilium in the family Liliaceae. We wished to investigate the immunoregulatory activities of the selenized polysaccharides of lily bulb (sLP). We undertook experiments in vitro and in vivo taking the unmodified polysaccharides of lily bulb (LP) as controls. The results of in vitro studies showed that sLP could promote the phagocytosis of RAW 264.7 cells significantly, increase the content of interleukin (IL)-1ß and IL-2, enhance the activity of acid phosphatase, and increase the surface molecular expression of CD86 and CD80. The results of in vivo studies showed that sLP could improve the index of immune organs, increase the contents of interferon-γ, IL-6, immunoglobulin (Ig)G and IgM in serum, and promote lymphocyte proliferation. The immunoregulatory activities of sLP were significantly more robust than those of LP in vitro and in vivo. These results indicated that selenylation could enhance the immune-enhancement activity of LP significantly.


Assuntos
Fatores Imunológicos/farmacologia , Lilium , Polissacarídeos/farmacologia , Animais , Linfócitos B/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citocinas/sangue , Citocinas/imunologia , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Camundongos , Fagocitose/efeitos dos fármacos , Raízes de Plantas , Células RAW 264.7 , Linfócitos T/efeitos dos fármacos
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