Fosfatasa alcalina intestinal: una enzima con propiedades antiinflamatorias
Resumen
Intestinal alkaline phosphatase: an enzyme with anti-inflammatory properties
Fosfatasse alcalina intestinal: uma enzima com propriedades anti-inflamatórias
Una de las principales funciones de la Fosfatasa Alcalina Intestinal (FAI) es la detoxificación de los lipopolisacáridos (LPS) bacterianos para controlar la inflamación intestinal. Recientes publicaciones indican que FAI participa en la detoxificación de otros compuestos bacterianos (flagelina y motivos CpG de DNA) y de muchos nucleótidos libres (ATP, UDP). FAI está involucrada de manera directa en la recuperación tisular de la inflamación por la Resolvina E1. La acción antiinflamatoria de FAI mejora indirectamente la función de la barrera intestinal e impacta la diversidad y la composición de la microbiota. Diversas enfermedades intestinales, incluyendo enterocolitis necrótica, enfermedad celíaca y la inflamación crónica intestinal (o inflammatory bowel disease, IBD) están relacionadas con disminuciones en la expresión y actividad de FAI. Por otro lado, una elevada actividad de FAI en colon es sinónimo de procesos inflamatorios, debido a la elevada concentración de la isoforma tisular de Fosfatasa Alcalina no específica (FANE), y a la infiltración tisular por los neutrófilos (que también contienen FANE). En algunos ensayos en humanos se ha observado que la administración exógena de FAI reduce la inflamación intestinal/sistémica (dependiendo de la vía de administración).. En conclusión, la homeóstasis intestinal y la preservación de la salud dependen en gran medida de la capacidad de FAI para detoxificar los LPS y suprimir la inflamación metabólica inducida por estos. Sin embargo, es necesario realizar investigaciones a fondo sobre como los hábitos alimenticios pueden modificar la detoxificación de los diferentes compuestos proinflamatorios bacterianos y maximizar la actividad de FAI.
Abstract:
One of the main functions of Intestinal Alkaline Phosphatase (FAI) is to detoxify bacterial lipopolysaccharides (LPS) to control intestinal inflammation. Recent data indicate that FAI participates in the detoxification of other bacterial compounds (flagellin and DNA CpG motifs) and many free nucleotides (ATP, UDP). FAI is directly involved in the resolution of tissue inflammation mediated by Resolvin E1. The anti-inflammatory action of FAI indirectly improves the intestinal barrier function and affects the diversity of microbiota. Various intestinal diseases, including necrotizing enterocolitis, celiac disease and chronic intestinal inflammation (inflammatory bowel disease) are related to a decrease in the expression and activity of FAI. Furthermore, a high FAI activity in the colon is related with inflammatory processes due to high concentration of tissue nonspecific alkaline phosphatase isoform (FANE) and tissue infiltration by neutrophils, which also contain FANE. Exogenous administration of FAI reduces intestinal and/or systemic inflammation (depending on the route of administration). In conclusion, intestinal homeostasis and health largely depend on the capacity of FAI to detoxify LPS and remove LPS-induced metabolic inflammation. However, how our diets can actually limit gut pools of pro-inflammatory bacterial compounds and maximize IAP activity needs more in-depth investigations.
Resumo
Uma das principais funções da Fosfatasse Alcalina Intestinal (FAI) é a detoxificação dos lipopolissacarídeos (LPS) bacterianos para controlar a inflamação intestinal. Recentes publicações indicam que a FAI participa na detoxificação de outros compostos bacterianos (flagelina e motivos CpG do DNA) e de muitos nucleotídeos libres (ATP, UDP). A FAI está involucrada de forma direita na recuperação tissular da inflamação pela Resolvina E1 (RvE1). A ação antiinflamatória da FAI melhora indiretamente a função da barreira intestinal e impacta a diversidade e a composição da microbiota. Diversas doenças intestinais, incluindo enterocolitis necrótica, doença celíaca e a inflamação crônica intestinal (inflammatory bowel disease, IBD) estão relacionados com diminuições na expressão e atividade da FAI. De outro jeito, uma elevada atividade da FAI no cólon é sinônimo de processos inflamatórios, devido a elevada concentração da isoforma tissular da Fosfatasse Alcalina não especifica (FANE), e a infiltração tissular pelos neutrófilos (que também contém FANE). A administração exógena da FAI reduz a inflamação intestinal/sistêmica (dependendo da via de administração) incluindo uns poucos testes no homem. Em conclusão, a homeostase intestinal e a preservação da saúde dependem em grande medida da capacidade da FAI para detoxificar os LPS e suprimir a inflamação metabólica induzida por estes. Embora, é preciso realizar pesquisas bem feitas sobre como os costumes alimentares podem modificar a detoxificação dos diferentes compostos proinflamatórios bacterianos e maximizar a atividade da FAI.
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