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      Inhibidores del NF-kB en la dieta y su papel en las enfermedades alérgicas Translated title: NF-kB inhibitors from diet and their role in allergic diseases

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          Abstract

          Resumen El NF-kB tiene un papel central como regulador de las respuestas inflamatoria e inmune. Se encuentra en forma inactiva en el citoplasma de las células. Después de la activación de estas, el NF-kB se disocia de su proteína inhibidora y se transloca al núcleo, donde participa en la transcripción de genes como los de las citoquinas inflamatorias, moléculas de adhesión, inmunoglobulinas y diversos receptores presentes en células de la respuesta inmune, entre otros. Este factor de transcripción posee un grupo de inhibidores fisiológicos y no fisiológicos. Dentro de los no fisiológicos se destacan algunos presentes en la dieta, como los carotenoides y los polifenoles, que reducen su actividad como inductor transcripcional. Diversos estudios epidemiológicos muestran que el consumo de frutas y verduras protege del desarrollo de alergias. Se ha postulado que este efecto protector se debe al contenido de polifenoles y carotenoides presentes en estos alimentos. Estos compuestos actúan en diversos niveles de la respuesta inmune de tipo alérgico. Inhibiendo las citoquinas Th2, el infiltrado de células inflamatorias en los tejidos, la síntesis de IgE y la liberación de mediadores farmacológicos, entre otras. Esto debido al efecto de estos compuestos sobre la fosforilación, ubiquitinación y degradación de diversas proteínas que participan en los procesos de inhibición y/o activación del NF-kB. En esta revisión analizamos aspectos moleculares del NF-kB y describimos inhibidores presentes en la dieta, como polifenoles y carotenoides, su papel en los procesos inflamatorios de tipo alérgico y en el desarrollo de enfermedades alérgicas.

          Translated abstract

          Abstract The NF-kB plays a central role as a regulator of the inflammatory and immune responses. It is found in inactive form in the cytoplasm of cells. After its activation, the NF-kB dissociates from an inhibitory protein and translocate to the nucleus where it participates in the transcription of genes such as inflammatory cytokines, adhesion molecules, immunoglobulins and various receptors on immune cells, among others. This transcription factor has a group of physiological and non-physiological inhibitors. Among the non-physiological, those present in the diet such as carotenoids and polyphenols reduce their activity as a transcriptional inducer. Epidemiological studies have shown that consumption of fruits and vegetables protect against development of allergies. It has been postulated that this protective effect is due to polyphenol and carotenoids present in those foods. These compounds act at various levels of the allergic immune response. Inhibiting Th2 cytokines, inflammatory cell infiltration into tissues, IgE synthesis and the release of pharmacological mediators among others. This is due to their effect on phosphorylation, ubiquitination and degradation of various proteins involved in the processes of inhibition and/or activation of NF-kB. In this review, we analyze molecular aspects of NF-kB and described inhibitors present in the diet, such as polyphenols and carotenoids, their role in allergic inflammatory process and the development of allergic diseases.

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          Most cited references61

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          Th2 Cytokines and Atopic Dermatitis.

          Atopic dermatitis (AD), a chronic relapsing inflammatory skin disease, is increasing in prevalence around the world. Intensive research is ongoing to understand the mechanisms involved in the development of AD and offer new treatment options for patients suffering from AD. In this review, we highlight the importance of allergic Th2 responses in the development of the disease and summarize relevant literature, including genetic studies, studies of human skin and mechanistic studies on keratinocytes and mouse models of AD. We discuss the importance of the skin barrier and review recent findings on the pro-Th2 cytokines TSLP, IL-25, and IL-33, notably their ability to polarize dendritic cells and promote Th2 responses. After a brief update on the contribution of different T-cell subsets to AD, we focus on Th2 cells and the respective contributions of each of the Th2 cytokines (IL-4, IL-13, IL-5, IL-31, and IL-10) to AD. We conclude with a brief discussion of the current gaps in our knowledge and technical limitations.
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            Transcriptional regulation via the NF-kappaB signaling module.

            Stimulus-induced nuclear factor-kappaB (NF-kappaB) activity, the central mediator of inflammatory responses and immune function, comprises a family of dimeric transcription factors that regulate diverse gene expression programs consisting of hundreds of genes. A family of inhibitor of kappaB (IkappaB) proteins controls NF-kappaB DNA-binding activity and nuclear localization. IkappaB protein metabolism is intricately regulated through stimulus-induced degradation and feedback re-synthesis, which allows for dynamic control of NF-kappaB activity. This network of interactions has been termed the NF-kappaB signaling module. Here, we summarize the current understanding of the molecular structures and biochemical mechanisms that determine NF-kappaB dimer formation and the signal-processing characteristics of the signaling module. We identify NF-kappaB-kappaB site interaction specificities and dynamic control of NF-kappaB activity as mechanisms that generate specificity in transcriptional regulation. We discuss examples of gene regulation that illustrate how these mechanisms may interface with other transcription regulators and promoter-associated events, and how these mechanisms suggest regulatory principles for NF-kappaB-mediated gene activation.
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              Luteolin suppresses inflammation-associated gene expression by blocking NF-κB and AP-1 activation pathway in mouse alveolar macrophages

              Luteolin, a plant flavonoid, has potent anti-inflammatory properties both in vitro and in vivo. However, the molecular mechanism of luteolin-mediated immune modulation has not been fully understood. In this study, we examined the effects of luteolin on the production of nitric oxide (NO) and prostaglandin E2 (PGE2), as well as the expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) in mouse alveolar macrophage MH-S and peripheral macrophage RAW 264.7 cells. Luteolin dose-dependently inhibited the expression and production of these inflammatory genes and mediators in macrophages stimulated with lipopolysaccharide (LPS). Semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) assay further confirmed the suppression of LPS-induced TNF- α, IL-6, iNOS and COX-2 gene expression by luteolin at a transcriptional level. Luteolin also reduced the DNA binding activity of nuclear factor-kappa B (NF-κB) in LPS-activated macrophages. Moreover, luteolin blocked the degradation of IκB-α and nuclear translocation of NF-κB p65 subunit. In addition, luteolin significantly inhibited the LPS-induced DNA binding activity of activating protein-1 (AP-1). We also found that luteolin attenuated the LPS-mediated protein kinase B (Akt) and IKK phosphorylation, as well as reactive oxygen species (ROS) production. In sum, these data suggest that, by blocking NF-κB and AP-1 activation, luteolin acts to suppress the LPS-elicited inflammatory events in mouse alveolar macrophages, and this effect was mediated, at least in part, by inhibiting the generation of reactive oxygen species. Our observations suggest a possible therapeutic application of this agent for treating inflammatory disorders in lung.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Journal
                sun
                Revista Salud Uninorte
                Salud, Barranquilla
                Fundación Universidad del Norte, División de Ciencias de la (Barranquilla, Atlantico, Colombia )
                0120-5552
                2011-7531
                December 2017
                : 33
                : 3
                : 464-476
                Affiliations
                [1] Bolívar orgnameUniversidad de Cartagena orgdiv1Instituto de Investigaciones Inmunológicas Colombia
                [2] Bolívar orgnameUniversidad de Cartagena orgdiv1Instituto de Investigaciones Inmunológicas Colombia
                Article
                S0120-55522017000300464
                d50b222d-8259-434f-978d-a03d2beceb05

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 10 October 2017
                : 20 May 2017
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 69, Pages: 13
                Product

                SciELO Colombia


                polifenoles,dieta,inhibidores,NF-kB,carotenoids,polyphenols,carotenoides,alergia,allergies,diet,inhibitor

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