RESUMO

A resposta imunológica é um processo complexo que envolve a interação e sinalização de diferentes tipos celulares e moleculares, conhecidos como biomarcadores, os quais atuam de modo coordenado para promover a defesa do organismo. Essa resposta inicia-se com a instalação do processo inflamatório, que culmina com eliminação de agentes microbianos e cicatrização do tecido afetado, podendo evoluir para uma resposta mais específica. Muitos mediadores produzidos durante essas reações, sobretudo aqueles de natureza lipídica e peptídica, podem ser originados da imunomodulação promovida por ácidos graxos insaturados fornecidos pela dieta ou sintetizados endogenamente. Ácidos graxos insaturados são constituintes das membranas celulares e reguladores da expressão gênica, atuando nas vias de sinalização, transdução de sinais e proliferação celular e gerando produtos que regulam os mecanismos da imunidade humoral e celular. Esses lipídios apresentam várias propriedades biológicas, incluindo importantes efeitos imunomoduladores sobre a inflamação e a cicatrização. Ácidos graxos insaturados regulam a ativação de diversas células envolvidas nesses processos, tais como macrófagos, neutrófilos, linfócitos, queratinócitos e células dendríticas, bem como a secreção de seus produtos, exercem efeitos sobre enzimas e fatores de transcrição gênica, estimulando ou inibindo a produção de eicosanóides, como as prostaglandinas e leucotrienos, citocinas, moléculas de adesão, fatores de crescimento e outras moléculas específicas envolvidas nas diferentes fases do reparo tecidual, além de modular o estresse oxidativo. Neste contexto, esse artigo tem como objetivo revisar o papel dos principais biomarcadores celulares e moleculares envolvidos na resposta imune-inflamatória modulada por ácidos graxos insaturados.(AU)

Immune response is a complex process that involves interaction and signaling of different cell and molecular types, known as biomarkers, which are organized to promote the defense of organism. This response begins with installation of the inflammatory process and culminates with elimination of the microbial agents, damage tissue and repair. The inflammatory response can progress to a more specific process. Many mediators are produced during inflammation, especially lipid and peptide mediators. These substances can be generated from immunomodulation promoted by unsaturated fatty acids provided by dietary or endogenously synthesized. Unsaturated fatty acids are constituents of cell membranes and regulators of gene expression and act on signaling pathways, signal transduction and cell proliferation, generating products that regulate the mechanisms of humoral and cellular immunity. These lipids have multiple biological properties, including important immunomodulatory effects on inflammation and wound healing. Unsaturated fatty acids regulate the activation of various cells involved in these processes, such as macrophages, neutrophils, lymphocytes, keratinocytes and dendritic cells, as well as secretion of their products, exert effects on enzymes and gene transcription factors by stimulating or inhibiting the production of eicosanoids as prostaglandins and leukotrienes, cytokines, adhesion molecules, growth factors and other specific molecules involved in different phases of tissue repair, and modulate oxidative stress. In this context, the aim of this paper is to review the role of main cellular and molecular biomarkers involved in immune-inflammatory response modulated by unsaturated fatty acids.(AU)

Assuntos

RESUMO

A resposta imunológica é um processo complexo que envolve a interação e sinalização de diferentes tipos celulares e moleculares, conhecidos como biomarcadores, os quais atuam de modo coordenado para promover a defesa do organismo. Essa resposta inicia-se com a instalação do processo inflamatório, que culmina com eliminação de agentes microbianos e cicatrização do tecido afetado, podendo evoluir para uma resposta mais específica. Muitos mediadores produzidos durante essas reações, sobretudo aqueles de natureza lipídica e peptídica, podem ser originados da imunomodulação promovida por ácidos graxos insaturados fornecidos pela dieta ou sintetizados endogenamente. Ácidos graxos insaturados são constituintes das membranas celulares e reguladores da expressão gênica, atuando nas vias de sinalização, transdução de sinais e proliferação celular e gerando produtos que regulam os mecanismos da imunidade humoral e celular. Esses lipídios apresentam várias propriedades biológicas, incluindo importantes efeitos imunomoduladores sobre a inflamação e a cicatrização. Ácidos graxos insaturados regulam a ativação de diversas células envolvidas nesses processos, tais como macrófagos, neutrófilos, linfócitos, queratinócitos e células dendríticas, bem como a secreção de seus produtos, exercem efeitos sobre enzimas e fatores de transcrição gênica, estimulando ou inibindo a produção de eicosanóides, como as prostaglandinas e leucotrienos, citocinas, moléculas de adesão, fatores de crescimento e outras moléculas específicas envolvidas nas diferentes fases do reparo tecidual, além de modular o estresse oxidativo. Neste contexto, esse artigo tem como objetivo revisar o papel dos principais biomarcadores celulares e moleculares envolvidos na resposta imune-inflamatória modulada por ácidos graxos insaturados.

Immune response is a complex process that involves interaction and signaling of different cell and molecular types, known as biomarkers, which are organized to promote the defense of organism. This response begins with installation of the inflammatory process and culminates with elimination of the microbial agents, damage tissue and repair. The inflammatory response can progress to a more specific process. Many mediators are produced during inflammation, especially lipid and peptide mediators. These substances can be generated from immunomodulation promoted by unsaturated fatty acids provided by dietary or endogenously synthesized. Unsaturated fatty acids are constituents of cell membranes and regulators of gene expression and act on signaling pathways, signal transduction and cell proliferation, generating products that regulate the mechanisms of humoral and cellular immunity. These lipids have multiple biological properties, including important immunomodulatory effects on inflammation and wound healing. Unsaturated fatty acids regulate the activation of various cells involved in these processes, such as macrophages, neutrophils, lymphocytes, keratinocytes and dendritic cells, as well as secretion of their products, exert effects on enzymes and gene transcription factors by stimulating or inhibiting the production of eicosanoids as prostaglandins and leukotrienes, cytokines, adhesion molecules, growth factors and other specific molecules involved in different phases of tissue repair, and modulate oxidative stress. In this context, the aim of this paper is to review the role of main cellular and molecular biomarkers involved in immune-inflammatory response modulated by unsaturated fatty acids.

Assuntos

RESUMO

Background: Inflammation is an adaptive response that is triggered by noxious stimuli and conditions, which involves interactions amongst many cell types and mediators, and underlies many pathological process. Unsaturated fatty acids (UFAs) can infl uence inflammation through a variety of mechanisms, and have been indicated as alternative anti-inflammatory agents to treat several inflammatory skin disorders. Pumpkin seed oil (PSO) is rich in UFAs, but its topical anti-inflammatory properties have not been investigated. Therefore, the aim of this paper was to evaluate the effects of PSO on acute and chronic cutaneous inflammation experimental models. Materials, Methods & Results: PSO was purchased commercially and analyzed phytochemically. The topical anti-inflammatory activity of PSO at different concentrations was evaluated on acute models (xylene- and 12-O-tetradecanoylphorbol acetate (TPA)-induced ear edema) and chronic model (multiple applications of oxazolone-induced dermatitis) in mice. Indomethacin and dexamethasone were used as reference drugs. The ear swelling was measured in both ear thickness (µm) and weight tissue (mg) at 1 and 4 h after xylene and TPA application, respectively. In the chronic model, the effectiveness of treatments was measured each 24 h post-challenge with oxazolone for 4 days. At the end of experiments, ear biopsies were assessed by histological analysis on hematoxylin-eosin- and toluidine blue-stained slides. Data were submitted to ANOVA followed Student Newman Keuls test (P < 0.05). PSO was characterized by a high content of unsaturated fatty acids (UFAs) (79.80%), including linoleic acid (ω-6, 55.83%) and oleic acid (ω-9, 23.47%). PSO caused a dose-dependent inhibition of xylene and TPA-induced ear edema in both skin thickness and weight when compared to respective positive controls (P < 0.05). This anti-inflammatory effects was maximum when PSO was applied in nature (inhibition of 69.9 ± 2.8% and 78.1 ± 7.7% for inflammation induced by xylene and TPA, respectively; P < 0.05), and was similar to, at least, one drug reference (P < 0.05). In addition, the topical treatment with PSO caused the inhibition of inflammation-induced by oxazolone in 60.9 ± 9.8% when compared to control positive (P < 0.05), which was similar to dexamethasone (68.7 ± 8.1%, P < 0.05). In histological analysis, PSO reduced the inflammatory parameters (edema, congestion, epidermal hyperplasia and cellular infiltration) in inflammation models studied. However, the number of mastocytes in cell infiltration was reduced (17.6 ± 4.0) when compared to positive control (39.4 ± 5.8 cells) in chronic model (P < 0.05), but no differences were observed in acute models. Discussion: Topical anti-inflammatory activity of plant-originated substances can be evaluated in several experimental models. In this study, we used as phlogistic agents: xylene, a promoter of neurogenic inflammation; TPA, a phorbol ester that activate protein kinase C, leading to production of lipid-derived mediators; and oxazolone, an inductor of contact delayed-type hypersensitivity. Our results suggest that PSO alter inflammatory response via modulation of cellular and molecular mediators involved in inflammatory pathways activated by theses phlogistic agents. In addition, this oil was able to resolve a persistent inflammatory lesion similar to dexamethasone, but we did not observe any cutaneous alterations caused by its topical use as related for corticosteroids. This is the first report on topical anti-inflammatory potential of PSO in acute and chronic skin inflammation. This activity may be attributed the proper balance of ω-6 and ω-9 UFAs present in PSO, suggesting this oil as alternative therapy for the treatment of inflammatory skin diseases. Further investigations are needed to support its application in clinical practice.

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