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1.
Clin Oral Investig ; 27(8): 4433-4446, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37285102

RESUMO

BACKGROUND: Single-blind 9 case comparative studies were conducted to evaluate salivary fluoride concentrations following toothbrushing using experimental toothpaste containing surface pre-reacted glass-ionomer (S-PRG) fillers. Preliminary tests were conducted in order to determine the volume of usage as well as the concentrations (wt %) of S-PRG filler. Based on the results given these experiments, we compared the salivary fluoride concentrations following toothbrushing with 0.5 g of 4 different types of toothpastes: 5 wt % S-PRG filler, 1400 ppm F AmF (amine fluoride), 1500 ppm F NaF (sodium fluoride), and MFP (monofluorophosphate) containing toothpaste. METHODS: Of the 12 participants, 7 participated in the preliminary study and 8 in the main study. All participants brushed their teeth using the scrubbing method for 2 min. At first, 1.0 and 0.5 g of 20 wt % S-PRG filler toothpastes were used to compare, then followed by 0.5 g of 0 (control), 1, and 5 wt % S-PRG toothpastes, respectively. The participants spat out once and rinsed with 15 mL of distilled water for 5 s. Saliva was collected for 3 min each at different time intervals of 0 (baseline), 5, 10, 15, 30, 60, 120, and 180 min after the rinsing. Fluoride concentrations were determined using a fluoride electrode, and the area under the salivary clearance - time curve (AUC: ppm‧min) of each toothpaste was calculated as the salivary fluoride retention. The main study was then conducted to evaluate the salivary fluoride concentrations as well as the AUC value using 0.5 g of 5 wt % S-PRG filler toothpaste, followed by NaF, MFP, and AmF toothpastes. RESULTS: Since there were no statistical differences between using 1.0 and 0.5 g of 20 wt % S-PRG toothpastes in salivary fluoride concentrations as well as the AUC value throughout the 180 min measurement, the volume was set as 0.5 g for the following studies. Concentrations of 5 and 20 wt % S-PRG toothpastes retained 0.09 ppm F or more in saliva even after 180 min. No statistical differences were seen in the salivary fluoride concentrations at any time intervals as well as the AUC value between 5 and 20 wt % S-PRG toothpastes. Based on these results, the concentration of 5 wt % S-PRG toothpaste was used for the main comparative study. MFP toothpaste resulted in by far the lowest salivary fluoride concentrations (0.06 ppm F at 180 min) and the AUC value (24.6 ppm‧min), whereas 5 wt % S-PRG toothpaste (0.15 ppm F at 180 min, 92.3 ppm‧min) displayed retention on par with AmF toothpaste which appeared to result in higher values (0.17 ppm F at 180 min, 103 ppm‧min), compared to NaF toothpaste (0.12 ppm F at 180 min, 49.3 ppm‧min). CONCLUSIONS: The salivary fluoride concentrations following toothbrushing with 0.5 g of 5 wt % S-PRG filler containing toothpaste showed retention similar to the best performing 1400 ppm F AmF toothpaste even 180 min after toothbrushing.


Assuntos
Fluoretos , Cremes Dentais , Humanos , Escovação Dentária/métodos , Método Simples-Cego , Fluoreto de Sódio , Cariostáticos
2.
Neurochem Int ; 140: 104848, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32920036

RESUMO

Brain edema following brain infarction affects mobility and mortality. The mechanisms underlying this process remain to be elucidated. Animal studies have shown that aquaporin-4 (AQP4) expression in astrocytes increases after stroke, and its deletion significantly reduces brain swelling. Recently, two kinds of cells, resident microglia-derived macrophage-like cells (MG-MΦ) and bone marrow-derived macrophages (BM-MΦ), have been reported to accumulate in the ischemic core and stimulate adjacent astrocytes. Therefore, we hypothesized that these cells play crucial roles in the expression of AQP4 and ultimately lead to exacerbated brain edema. To verify this hypothesis, we investigated the role of MG- or BM-MΦ in brain edema using a rat model of transient middle cerebral artery occlusion and rat astrocyte primary cultures. AQP4 expression significantly increased in the peri-infarct tissue at 3-7 days post-reperfusion (dpr) and in the core tissue at 5 and 7 dpr, which synchronized with the expression of Iba1, Il1a, Tnf, and C1qa mRNA. Interleukin (IL)-1α treatment or coculture with MG- and BM-MΦ increased AQP4 expression in astrocytes, while an IL-1 receptor type I antagonist reduced these effects. Furthermore, aggravated animals exhibited high expression of Aqp4 and Il1a mRNA in the ischemic core at 7 dpr, which led to the exacerbation of brain edema. MG-MΦ signature genes were highly expressed in the ischemic core in aggravated rats, while BM-MΦ signature genes were weakly expressed. These findings suggest that IL-1α produced by MG-MΦ induces astrocytic AQP4 expression in the peri-infarct and ischemic core tissues, thereby exacerbating brain edema. Therefore, the regulation of MG-MΦ may prevent the exacerbation of brain edema.


Assuntos
Aquaporina 4/biossíntese , Astrócitos/metabolismo , Edema Encefálico/metabolismo , Interleucina-1alfa/biossíntese , AVC Isquêmico/metabolismo , Macrófagos/metabolismo , Microglia/metabolismo , Animais , Aquaporina 4/genética , Edema Encefálico/genética , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Células Cultivadas , Expressão Gênica , Células HEK293 , Humanos , Interleucina-1alfa/genética , AVC Isquêmico/genética , Masculino , Ratos , Ratos Wistar
3.
Sci Rep ; 10(1): 1877, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-32024924

RESUMO

Numerous dark-brown-coloured small spots called "Wischnewski spots" are often observed in the gastric mucosa in the patients dying of hypothermia, but the molecular mechanisms through which they develop remain unclear. We hypothesised that hypothermia may activate the secretion of gastric acid and pepsin, leading to the development of the spots. To investigate this, we performed experiments using organotypic rat gastric tissue slices cultured at 37 °C (control) or 32 °C (cold). Cold loading for 6 h lowered the extracellular pH in the culture medium. The mRNA expression of gastrin, which regulates gastric acid secretion, increased after cold loading for 3 h. Cold loading increased the expression of gastric H+,K+-ATPase pump protein in the apical canalicular membrane and resulted in dynamic morphological changes in parietal cells. Cold loading resulted in an increased abundance of pepsin C protein and an elevated mRNA expression of its precursor progastricsin. Collectively, our findings clarified that cold stress induces acidification by activating gastric H+,K+-ATPase pumps and promoting pepsin C release through inducing progastricsin expression on the gastric mucosa, leading to tiny haemorrhages or erosions of the gastric mucosa that manifest as Wischnewski spots in fatal hypothermia.


Assuntos
Mucosa Gástrica/patologia , Hipotermia/mortalidade , Células Parietais Gástricas/metabolismo , Púrpura/patologia , Animais , Membrana Celular/metabolismo , Temperatura Baixa/efeitos adversos , Modelos Animais de Doenças , Mucosa Gástrica/citologia , Mucosa Gástrica/metabolismo , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Humanos , Hipotermia/etiologia , Hipotermia/patologia , Masculino , Células Parietais Gástricas/citologia , Pepsina A/metabolismo , Pepsinogênio C/metabolismo , Púrpura/etiologia , Ratos
4.
Am J Respir Cell Mol Biol ; 37(3): 322-9, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17507665

RESUMO

Glutathione is the major intracellular redox buffer. We have shown that glutathione redox status, which is the balance between intracellular reduced (GSH) and oxidized (GSSG) glutathione, in antigen-presenting cells (APC) regulates the helper T cell type 1 (Th1)/Th2 balance due to the production of IL-12. Bronchial asthma is a typical Th2 disease. Th2 cells and Th2 cytokines are characteristic of asthma and trigger off an inflammation. Accordingly, we studied the effects of the intracellular glutathione redox status on airway hyperresponsiveness (AHR) and allergen-induced airway inflammation in a mouse model of asthma. We used gamma-Glutamylcysteinylethyl ester (gamma-GCE), which is a membrane-permeating GSH precursor, to elevate the intracellular GSH level and GSH/GSSG ratio of mice. In vitro, gamma-GCE pretreatment of human monocytic THP-1 cells elevated the GSH/GSSG ratio and enhanced IL-12(p70) production induced by LPS. In the mouse asthma model, intraperitoneal injection of gamma-GCE elevated the GSH/GSSG ratio of lung tissue and reduced AHR. gamma-GCE reduced levels of IL-4, IL-5, IL-10, and the chemokines eotaxin and RANTES (regulated on activation, normal T cell expressed and secreted) in bronchoalveolar lavage fluid, whereas it enhanced the production of IL-12 and IFN-gamma. Histologically, gamma-GCE suppressed eosinophils infiltration. Interestingly, we also found that gamma-GCE directly inhibited chemokine-induced eosinophil chemotaxis without affecting eotaxin receptor chemokine receptor 3 (CCR3) expressions. Taken together, these findings suggest that changing glutathione redox balance, increase in GSH level, and the GSH/GSSG ratio by gamma-GCE, ameliorate bronchial asthma by altering the Th1/Th2 imbalance through IL-12 production from APC and suppressing chemokine production and eosinophil migration itself.


Assuntos
Glutationa/metabolismo , Inflamação/metabolismo , Sistema Respiratório/metabolismo , Animais , Asma/imunologia , Asma/metabolismo , Asma/fisiopatologia , Linhagem Celular , Quimiocinas/metabolismo , Quimiotaxia de Leucócito/efeitos dos fármacos , Citocinas/metabolismo , Dipeptídeos/farmacologia , Modelos Animais de Doenças , Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Feminino , Dissulfeto de Glutationa/metabolismo , Humanos , Inflamação/imunologia , Inflamação/fisiopatologia , Camundongos , Camundongos Endogâmicos BALB C , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Monócitos/metabolismo , Oxirredução , Receptores CCR3/metabolismo , Sistema Respiratório/efeitos dos fármacos , Sistema Respiratório/imunologia , Sistema Respiratório/fisiopatologia , Células Th1/imunologia , Células Th1/metabolismo , Células Th2/imunologia , Células Th2/metabolismo
5.
Invest Ophthalmol Vis Sci ; 45(2): 448-54, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14744884

RESUMO

PURPOSE: A Th1-type immune response was detected in allotransplanted, rejected corneas. Because the intracellular thiol redox status of antigen-presenting cells (APCs) reportedly regulates the Th1/Th2 balance through distinctive cytokine production by APCs, this study was conducted to investigate the effect of the intracellular thiol redox status of macrophages (Mps) on corneal allograft survival. METHODS: N,N'-diacetyl-L-cystine dimethylester (NACOMe)(2) was injected intraperitoneally into BALB/c (H-2(d)) mice to induce Mps with a low intracellular glutathione content (icGSH). Corneal grafts from C57BL/10 (H-2(b)), B10.D2 (H-2(d)), and DBA/2 (H-2(d)) donor mice were placed on neovascularized BALB/c graft beds for assessment. B10.D2-grafted recipients were evaluated for donor-specific delayed-type hypersensitivity (DTH), and the cytokines produced by their lymphocytes were examined (IFN-gamma, IL-4, and IL-10). In other experiments, naïve BALB/c mice, injected intravenously with Mps of low icGSH content, received B10.D2 corneal grafts. RESULTS: In (NACOMe)(2)-treated mice, 13 of 20 B10.D2 grafts and 6 of 10 DBA/2 grafts survived indefinitely. No grafts survived in the control mice (P < 0.0001). (NACOMe)(2) treatment did not enhance C57BL/10 graft survival. At 2 weeks after B10.D2 grafting, control mice exhibited DTH, but (NACOMe)(2)-treated mice did not (P < 0.01). Lymphocytes from (NACOMe)(2)-treated mice did not respond to donor splenocytes. Those of control mice showed Th1-type cytokine secretion. The intravenous transfer of peritoneal Mps from (NACOMe)(2)-treated mice prolonged corneal allograft survival (P < 0.003). CONCLUSIONS: The observed enhanced graft acceptance may be due to the suppression of alloantigen-induced Th1 polarization through the induction of Mps with reduced icGSH levels.


Assuntos
Córnea/fisiologia , Transplante de Córnea/fisiologia , Cistina/análogos & derivados , Sobrevivência de Enxerto/fisiologia , Macrófagos Peritoneais/fisiologia , Transferência Adotiva , Animais , Divisão Celular , Cistina/farmacologia , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Glutationa/metabolismo , Hipersensibilidade Tardia/imunologia , Ativação de Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Oxirredução , Células Th1/fisiologia , Transplante Homólogo
6.
J Immunol ; 171(2): 628-35, 2003 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-12847227

RESUMO

Although c-Jun N-terminal kinase (JNK) plays an important role in cytokine expression, its function in IL-12 production is obscure. The present study uses human macrophages to examine whether the JNK pathway is required for LPS-induced IL-12 production and defines how JNK is involved in the regulation of IL-12 production by glutathione redox, which is the balance between intracellular reduced (GSH) and oxidized glutathione (GSSG). We found that LPS induced IL-12 p40 protein and mRNA in a time- and concentration-dependent manner in PMA-treated THP-1 macrophages, and that LPS activated JNK and p38 mitogen-activated protein (MAP) kinase, but not extracellular signal-regulated kinase, in PMA-treated THP-1 cells. Inhibition of p38 MAP kinase activation using SB203580 dose dependently repressed LPS-induced IL-12 p40 production, as described. Conversely, inhibition of JNK activation using SP600125 dose dependently enhanced both LPS-induced IL-12 p40 production from THP-1 cells and p70 production from human monocytes. Furthermore, JNK antisense oligonucleotides attenuated cellular levels of JNK protein and LPS-induced JNK activation, but augmented IL-12 p40 protein production and mRNA expression. Finally, the increase in the ratio of GSH/GSSG induced by glutathione reduced form ethyl ester (GSH-OEt) dose dependently enhanced LPS-induced IL-12 p40 production in PMA-treated THP-1 cells. GSH-OEt augmented p38 MAP kinase activation, but suppressed the JNK activation induced by LPS. Our findings indicate that JNK negatively affects LPS-induced IL-12 production from human macrophages, and that glutathione redox regulates LPS-induced IL-12 production through the opposite control of JNK and p38 MAP kinase activation.


Assuntos
Regulação para Baixo/imunologia , Glutationa/análogos & derivados , Glutationa/metabolismo , Interleucina-12/antagonistas & inibidores , Interleucina-12/biossíntese , Lipopolissacarídeos/farmacologia , Macrófagos/enzimologia , Macrófagos/imunologia , Proteínas Quinases Ativadas por Mitógeno/fisiologia , Antracenos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Células Cultivadas , Ativação Enzimática/imunologia , Inibidores Enzimáticos/farmacologia , Glutationa/farmacologia , Humanos , Imidazóis/farmacologia , Interleucina-12/genética , Interleucina-12/metabolismo , Subunidade p40 da Interleucina-12 , Proteínas Quinases JNK Ativadas por Mitógeno , Lipopolissacarídeos/antagonistas & inibidores , Sistema de Sinalização das MAP Quinases/genética , Sistema de Sinalização das MAP Quinases/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Proteína Quinase 8 Ativada por Mitógeno , Proteína Quinase 9 Ativada por Mitógeno , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Oligonucleotídeos Antissenso/farmacologia , Oxirredução , Subunidades Proteicas/antagonistas & inibidores , Subunidades Proteicas/biossíntese , Subunidades Proteicas/genética , Piridinas/farmacologia , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/biossíntese , Células Tumorais Cultivadas , Regulação para Cima/genética , Regulação para Cima/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno
7.
Eur J Immunol ; 33(4): 1001-11, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12672066

RESUMO

The redox status of macrophages (M phi), indexed by intracellular content of glutathione (icGSH), varies sequentially along with disease progression in nonobese diabetic mice. At the stage of early insulitis, M phi skew to oxidative M phi (OM phi) with decreased icGSH, then to reductive M phi (RM phi) with elevated icGSH and to OM phi after the occurrence of diabetes. RM phi or OM phi inducing agents either delayed or accelerated the onset of diabetes in a mutually inverse manner. RM phi or OM phi adoptively transferred exacerbated or ameliorated the disease progression depending on the redox status of M phi of recipient mice. The new paradigm that the sequential conversion of redox status of M phi dictates the pathological progression may provide a new insight on the mechanism underlying autoimmune diabetes.


Assuntos
Diabetes Mellitus Tipo 1/imunologia , Macrófagos/metabolismo , Transferência Adotiva , Animais , Ciclofosfamida/farmacologia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patologia , Progressão da Doença , Feminino , Glutationa/análise , Cinética , Macrófagos/química , Macrófagos/transplante , Camundongos , Camundongos Endogâmicos NOD , Oxirredução/efeitos dos fármacos , Fenótipo , Compostos de Sulfidrila/farmacologia , Células Th1/imunologia , Células Th2/imunologia
8.
Eur J Immunol ; 32(10): 2866-73, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12355439

RESUMO

Murine mature splenic DC with elevated intracellular glutathione, pretreated with IL-18, strikingly augmented the production of IFN-gamma in response to IL-12, whereas intracellular glutathione deprivation ablated this effect of IL-18. Likewise, macrophages with elevated intracellular glutathione augmented IFN-gamma production upon LPS or IL-12+IL-18 stimulation, whereas macrophages with reduced intracellular glutathione showed the reciprocal response. Under hypoxia, macrophages displayed a functional phenotype with decreased intracellular glutathione, i.e. decreased NO and IL-12, and elevated IL-10 production. However, mature DC and macrophages produced an elevated amount of IFN-gamma under hypoxia. Taken together, our results suggest that the intracellular redox status of DC and macrophages may play a pivotal role in local innate immunity, depending on local oxygen tension.


Assuntos
Células Apresentadoras de Antígenos/metabolismo , Citocinas/biossíntese , Glutationa/metabolismo , Hipóxia/imunologia , Interferon gama/biossíntese , Animais , Células Dendríticas/metabolismo , Interleucina-10/biossíntese , Interleucina-12/biossíntese , Interleucina-18/biossíntese , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Oxirredução
9.
Int Immunol ; 14(6): 627-36, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12039914

RESUMO

The distinct thiol redox status in macrophages, either elevated or reduced intracellular content of glutathione (GSH), was confirmed during aging in IL-2 receptor (IL-2R)gamma and Janus family tyrosine kinase (JAK)3 gene-disrupted mice. Oxidative macrophages (OMp) with reduced GSH dominated initially at a younger age in both mice. OMp-dominated JAK3 or IL-2R gamma chain-deficient mice showed shortened life longevity compared with wild-type littermates. These mice elicited spontaneous onsets of inflammatory bowel disease (IBD)-like symptoms accompanied with the conversion of the redox status of macrophages to reductive phenotypes with elevated intracellular GSH. Conversion of OMp to the reductive phenotype by GSH monoethyl ester or by a beta-(1-3)-glucan accelerated the disease onset, concomitant with the skewing from T(h)2 to T(h)1 responses. On the contrary, N,N'-diacetyl cystine dimethylester, which is capable of inducing OMp, delayed the incidence of IBD-like symptoms and improved the survival rate. This implies that the conversion of OMp/T(h)2 to reductive macrophages/T(h)1 may be critical for the disease progression. The study of these mice may provide insight into the mechanisms underlying Crohn's disease and ulcerative colitis.


Assuntos
Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/metabolismo , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/metabolismo , Proteínas Tirosina Quinases/deficiência , Receptores de Interleucina-2/deficiência , Animais , Citocinas/farmacologia , Modelos Animais de Doenças , Glutationa/metabolismo , Humanos , Técnicas In Vitro , Doenças Inflamatórias Intestinais/etiologia , Doenças Inflamatórias Intestinais/patologia , Janus Quinase 3 , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oxirredução , Proteínas Tirosina Quinases/genética , Receptores de Interleucina-2/genética , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia
10.
Int Immunopharmacol ; 2(5): 673-89, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12013506

RESUMO

In vivo lentinan (LNT)-elicited peritoneal macrophages (Mps) showed the reduced release of prostaglandins (PGs), IL-10 and IL-6, while it endowed Mps with the elevated capability to produce IL-12 and nitric oxide (NO) upon in vitro triggering, due to the elevated intracellular glutathione (GSH) content in Mps. Deprivation of intracellular GSH completely ablated the production of IL-12. Conversely, lipopolysaccharide (LPS) induced peritoneal Mps with the reduced intracellular GSH content and the reciprocal profile of mediator production. Mps with the elevated intracelluar GSH is arbitrarily termed as reductive Mp (RMp) and that with reduced amount as oxidative Mp (OMp). OMp was converted to RMp when GSH was replenished with glutathione monoethylester (GSH-OEt). The IL-2 administration in combination with LNT exerted the synergistic induction of RMp, resulting in synergistic augmentation of IL-12, NO and reduction of IL-6 production. It was also confirmed that CD4+T cells derived of LNT-administered mice showed augmented IFN-gamma and reduced IL-4 production upon in vitro anti-CD3 stimulation. Taken together it is concluded that skewing of Th1/Th2 balance to Th1 by a beta-(1-3)-glucan, LNT, is directed through the distinctive production of IL-12 versus IL-6, IL-10 and prostaglandin E2 (PGE2) by Mps, depending on intracellular GSH redox status. To the efficient tumor immunotherapy, it may be one of the critical elements to induce a reductive form of Mps in tumor stromal tissues to maintain Th1 response.


Assuntos
Citocinas/biossíntese , Glutationa/biossíntese , Líquido Intracelular/efeitos dos fármacos , Lentinano/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Células Th1/efeitos dos fármacos , Animais , Feminino , Glutationa/metabolismo , Líquido Intracelular/imunologia , Líquido Intracelular/metabolismo , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Células Th1/imunologia , Células Th1/metabolismo
11.
Int Immunol ; 14(2): 201-12, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11809739

RESUMO

We have been proposing the functional discrimination of two classes of macrophages (Mp), i.e. reductive macrophages (RMp) with a high intracellular content of glutathione and oxidative macrophages (OMp) with a reduced content. In this paper we will present the evidence that the T(h)1/T(h)2 balance is regulated by the balance between RMp and OMp due to the disparate production of IL-12 versus IL-6 and IL-10. RMp were induced by in vivo application of N-acetyl-L-cysteine or glutathione monoethylester and OMp by L-cystine derivatives, diethyl maleate or L-buthionine-[S,R]-sulfoximine. The Mp arbitrarily called OMp showed elevated IL-6 and IL-10 production, and reduced NO and IL-12 production. The RMp elicited a reciprocal response, i.e. elevated IL-12 and NO production, and reduced IL-6 and IL-10 production. The cytokine propensities of OMp or RMp were inter-converted to each other. The results were also confirmed by using auto-MACS purified F4/80(+) Mp without adherence. Interestingly, IFN-gamma induced RMp and augmented NO generation with decreased production of IL-6, whilst IL-4 induced OMp and augmented IL-6 production. CD4(+)CD44(-) naive T(h)0 cells were differentiated preferentially either to T(h)l or T(h)2 cells, depending on the presence of RMp or OMp during the initial 24 h of culture, from ovalbumin-specific TCR-transgenic mouse spleen cells in the presence of IL-2. Taken together, RMp induction may generate the amplification loop of a RMp/T(h)1 circuit and OMp that of OMp/T(h)2. The findings implicate that the alteration in Mp functions because altered intracellular glutathione may play a relevant role in the pathological progression of inflammation.


Assuntos
Citocinas/biossíntese , Macrófagos/metabolismo , Compostos de Sulfidrila/metabolismo , Células Th1/fisiologia , Células Th2/fisiologia , Transferência Adotiva , Animais , Polaridade Celular , Interferon gama/farmacologia , Interleucina-10/biossíntese , Interleucina-12/biossíntese , Interleucina-4/farmacologia , Interleucina-6/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Óxido Nítrico/biossíntese , Oxirredução
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