RESUMEN
Celiac Disease (CeD) is a chronic immune-mediated enteropathy, in which dietary gluten induces an inflammatory reaction, predominantly in the duodenum. Propolis is a resinous hive product, collected by honeybees from various plant sources. Propolis is well-known for its anti-inflammatory, anti-oxidant and immunomodulatory effects, due to its major compounds, polyphenols and flavonoids. The aim of our study was to assess the ex vivo effect of ethanolic extract of propolis (EEP) upon the activity and expression of iNOS, along with IFN-γ and IL-10 production in Algerian Celiac patients. In this context, PBMCs isolated from peripheral blood of Celiac patients and healthy controls were cultured with different concentrations of EEP. NO production was measured using the Griess method, whereas quantitation of IFN-γ and IL-10 levels was performed by ELISA. Inducible nitric oxide synthase (iNOS) expression, NFκB and pSTAT-3 activity were analyzed by immunofluorescence assay. Our results showed that PBMCs from Celiac patients produced high levels of NO and IFN-γ compared with healthy controls (HC). Interestingly, EEP reduced significantly, NO and IFN-γ levels and significantly increased IL-10 levels at a concentration of 50 µg/mL. Importantly, EEP downmodulated the iNOS expression as well as the activity of NFκB and pSTAT-3 transcription factors. Altogether, our results highlight the immunomodulatory effect of propolis on NO pathway and on pro-inflammatory cytokines. Therefore, we suggest that propolis may constitute a potential candidate to modulate inflammation during Celiac Disease and has a potential therapeutic value.
Asunto(s)
Enfermedad Celíaca/tratamiento farmacológico , Factores Inmunológicos/uso terapéutico , Óxido Nítrico/fisiología , Própolis/uso terapéutico , Adolescente , Adulto , Niño , Etanol , Femenino , Flavonoides/química , Flavonoides/farmacología , Humanos , Interferón gamma/biosíntesis , Interleucina-10/biosíntesis , Masculino , Persona de Mediana Edad , FN-kappa B/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo II/biosíntesis , Polifenoles/química , Polifenoles/farmacología , Própolis/química , Factor de Transcripción STAT3/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Solventes , Adulto JovenRESUMEN
Primary Sjögren's syndrome (pSS) is a systemic autoimmune disorder with a complex pathophysiology primarily affecting exocrine glands, leading to compromised secretory function. Recent studies imply that many inflammatory mediators, such as pro-inflammatory cytokines and nitric oxide, are critical in the development and perpetuation of pSS systemic manifestations. In the current study, we aimed to investigate the ex vivo immunomodulatory effect of cardamonin (C16H14O4), on pro-inflammatory cytokines, TNF-α, IL-6 and inducible nitric oxide synthase (iNOS) expression during pSS. For this purpose, peripheral blood mononuclear cells isolated from pSS patients and healthy controls were cultured with different concentrations of cardamonin. Cytokine levels were measured by ELISA and NO production was assessed using the Griess method. Inducible nitric oxide synthase expression and NF-κB activity were analyzed by immunofluorescence staining. Our results suggest that cardamonin inhibits TNF-α, IL-6 and NO production and downregulates iNOS expression and NF-κB activation. Collectively, our results highlight the ex vivo immunomodulatory effects of cardamonin on pro-inflammatory cytokine production and NO pathway in pSS patients. Therefore, cardamonin is a potential candidate for controlling inflammation during pSS.
Asunto(s)
Chalconas/farmacología , Interleucina-6/metabolismo , Leucocitos Mononucleares/metabolismo , Óxido Nítrico/metabolismo , Síndrome de Sjögren/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Adulto , Femenino , Humanos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Leucocitos Mononucleares/patología , Masculino , Persona de Mediana Edad , Óxido Nítrico Sintasa de Tipo II/metabolismo , Síndrome de Sjögren/tratamiento farmacológico , Síndrome de Sjögren/patologíaRESUMEN
Behçet's disease (BD) is an inflammatory multisystemic disorder associated with orogenital ulcers, uveitis and skin lesions with unpredictable episodes of exacerbations and remissions. Even though several immunological and environmental factors contribute to BD progression, its ethiopathogenesis remains uncertain and elusive. Considered as one of the potent environmental factors that can increase prevalence of some autoimmune and inflammatory disorders, vitamin D deficiency has been linked to several diseases as BD. The aim of this study is to assess vitamin D status in Algerian BD patients and its relationship with disease activity. Immunomodulatory effect of this vitamin on nitric oxide (NO), inflammatory mediator, was also undertaken. Serum 25(OH) vitamin D levels were measured in healthy controls (HC), active and inactive BD patients with an electrochemiluminescence method. After treatment of HCs' and patients' peripheral blood mononuclear cells with different concentrations of vitamin D3, NO production was evaluated with Griess method, while inducible nitric oxide synthase (iNOS) and NF-κB expression with immunofluorescence test. A high decrease of vitamin D levels was noted in active BD patients compared to those of inactive stage and HC. However, a higher NO production was observed during active stage of BD compared to inactive one. In inactive BD, vitamin D levels correlates negatively with NO. Interestingly, vitamin D3 inhibits ex vivo NO production, iNOS and NF-κB expression in BD patients. In conclusion, vitamin D deficiency was associated with active BD. This vitamin down-modulates NO production in BD patients, suggesting that it may be considered as promising therapy modulating inflammation during BD.
Asunto(s)
Síndrome de Behçet/sangre , Síndrome de Behçet/inmunología , Factores Inmunológicos/inmunología , Óxido Nítrico/inmunología , Transducción de Señal/inmunología , Vitamina D/sangre , Adulto , Anciano , Femenino , Humanos , Inflamación/sangre , Inflamación/inmunología , Leucocitos Mononucleares/inmunología , Masculino , Persona de Mediana Edad , FN-kappa B/inmunología , Óxido Nítrico Sintasa de Tipo II/inmunología , Adulto JovenRESUMEN
Rheumatoid arthritis (RA) is a chronic autoimmune disease. The pathophysiology of RA implicates several mediators such as nitric oxide (NO) and cytokines such as interleukin-6 (IL-6), which is deeply involved in the main characteristics of RA. Furthermore, all-trans retinoic acid (ATRA) is an active vitamin A derivative well-known to have diverse immunomodulatory actions. In our study, we investigated first, the ex vivo immunomodulatory potential of ATRA on NO pathway by peripheral blood mononuclear cells (PBMCs) from Algerian RA patients. Then, we assessed the possible regulatory effect of ATRA on NO production induced by IL-6. PBMCs isolated from active and inactive RA patients and healthy controls were cultured with different concentrations of IL-6 or/with ATRA. NO production was assessed using the Griess method. Inducible nitric oxide synthase expression and NF-κB activity were analyzed by immunofluorescence test. Our results revealed a high NO production during active RA. We noticed that while IL-6 induced a high NO production and iNOS expression, ATRA downregulated both. ATRA also inhibited nuclear NF-κB translocation. Interestingly, it seems that NO production mediated by IL-6 on PBMCs of RA patients is downregulated by ATRA. Taken together, our results highlight the immunomodulatory effect of ATRA on NO pathway in RA patients and its possible role in regulating IL-6-mediated NO production. All these findings suggest its potential therapeutic role during RA.
Asunto(s)
Antiinflamatorios/farmacología , Artritis Reumatoide/inmunología , Interleucina-6/inmunología , Leucocitos Mononucleares/inmunología , Óxido Nítrico/inmunología , Tretinoina/farmacología , Adulto , Anciano , Argelia , Artritis Reumatoide/patología , Femenino , Humanos , Leucocitos Mononucleares/patología , Masculino , Persona de Mediana EdadRESUMEN
Alzheimer's disease (AD) is a neurodegenerative disease leading to a progressive and irreversible loss of mental functions. It is characterized by 3 stages according to the evolution and the severity of the symptoms. This disease is associated with an immune disorder, which appears with significant rise in the inflammatory cytokines and increased production of free radicals such as nitric oxide (NO). Our study aims to investigate interferon (IFN)-γ and tumor necrosis factor-α (TNF-α) involvement in NO production, in vivo and ex vivo, in peripheral blood mononuclear cells from Algerian patients (n=25), according to the different stages of the disease (mild Alzheimer's, moderate Alzheimer's, and severe Alzheimer's) in comparison to mild cognitive impairment (MCI) patients. Interestingly, we observed that in vivo IFN-γ and TNF-α levels assessed in patients with AD in mild and severe stages, respectively, are higher than those observed in patients with moderate stage and MCI. Our in vivo and ex vivo results show that NO production is related to the increased levels of IFN-γ and TNF-α, in mild and severe stages of AD. Remarkably, significant IFN-γ level is only detected in mild stage of AD. Our study suggests that NO production is IFN-γ dependent both in MCI and mild Alzheimer's patients. Further, high levels of NO are associated with an elevation of TNF-α levels in severe stage of AD. Collectively, our data indicate that the proinflammatory cytokine production seems, in part, to be involved in neurological deleterious effects observed during the development of AD through NO pathway.
Asunto(s)
Enfermedad de Alzheimer/inmunología , Disfunción Cognitiva/inmunología , Interferón gamma/inmunología , Leucocitos Mononucleares/inmunología , Óxido Nítrico/biosíntesis , Factor de Necrosis Tumoral alfa/inmunología , Anciano , Anciano de 80 o más Años , Argelia , Progresión de la Enfermedad , Femenino , Humanos , Mediadores de Inflamación/sangre , Interferón gamma/sangre , Masculino , Óxido Nítrico/metabolismo , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Uveitis, recurrent oral and genital ulcerations associated with skin lesions are the major symptoms of a chronic multisystemic inflammatory disorder known as Behçet's disease (BD). High prevalence of this dreaded disease has been observed in the Mediterranean basin, including Algeria and along the Silk Road. Although the etiologic agent of this disease remains uncertain, many hypotheses have been advanced in its pathogenesis. Our team has previously reported high levels of nitric oxide (NO) in sera of BD patients, suggesting its deleterious effect during chronic inflammation. In our current study, the aim is to investigate the ex vivo immunomodulatory effect of all-trans-retinoic acid (ATRA) on NO pathway in Algerian BD patients. First, peripheral blood mononuclear cells isolated from active and inactive BD patients and healthy controls were cultured with different concentrations of ATRA. NO production was estimated with the Griess method. To elucidate the underlying mechanisms of ATRA effect on NO production, we analyze inducible nitric oxide synthase expression and nuclear factor-κB (NF-κB) activity by immunofluorescence test. Our results revealed a higher production of NO in active BD compared with the inactive stage and healthy controls. We observed that ATRA inhibits NO production in BD both in active and inactive stages and inhibits NF-κB translocation. In conclusion, we report a relationship between NO production and the disease activity. ATRA down-regulates NO production in BD patients. This immunomodulatory effect seems to be mediated through NF-κB pathway. All these findings suggest that ATRA could be considered as a promising therapy for BD.