RESUMO
In this study, we investigated whether Heracleum (H) moellendorffii Hance-derived dehydrogeijerin and geijerin could be used to suppress lipopolysaccharide (LPS)-induced inflammatory responses in murine macrophage cell lines, Raw 264.7 cells. Dehydrogeijerin reduced nitric oxide (NO) and inducible nitric oxide synthase (iNOS) production from LPS-stimulated Raw 264.7 cells, but on the other hand, geijerin did not reduce NO production. Dehydrogeijerin, unlike geijerin, has a double bond at C2'-C3' with an oxo function at C1'. Pre-treatment of Raw 264.7 cells with dehydrogeijerin reduced the production of cyclooxigenase-2 (COX-2) and pro-inflammatory cytokines. These inhibitory effects were associated with decreases in the phosphorylation of mitogen-activated protein (MAP) kinases. Our results indicate that dehydrogeijerin significantly inhibits the inflammatory activity of activated macrophages, suggesting that dehydrogeijerin could be a potential candidate for the treatment of inflammatory disease.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Cromonas/farmacologia , Cumarínicos/farmacologia , Lipopolissacarídeos/toxicidade , Macrófagos/efeitos dos fármacos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cromonas/química , Cumarínicos/química , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Heracleum/química , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/química , Transdução de SinaisRESUMO
In this study, we investigate the relationship between natural killer (NK) cell susceptibility and the surface markers of cancer cells. Through phenotypic analysis, we found evidence that more susceptible cancer cell lines (K562 and Jurkat) express more NKG2D ligands. Major histocompatibility complex (MHC) class I chain-related A/B (MIC-A/B) and UL16 binding protein (ULBP) 1-5 molecules are typical ligands of NKG2D. The high killing activity of NK cells against K562 was abolished through the addition of a NKG2D blocking antibody. Upon in vitro stimulation with quercetin, low susceptible cancer cells increased NKG2D ligand expression, leading to enhancement of NK cell cytolytic activity. These results suggested that the anti-cancer activity of NK cells is not dependent on the origin and growth style of the target cells, but is dependent on the surface markers of the target cells.
Assuntos
Citotoxicidade Imunológica , Proteínas Ligadas por GPI/imunologia , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Células Matadoras Naturais/imunologia , Subfamília K de Receptores Semelhantes a Lectina de Células NK/imunologia , Linhagem Celular , Humanos , Ligantes , Neoplasias/imunologiaRESUMO
Protopine is an isoquinoline alkaloid contained in plants in northeast Asia. In this study, we investigated whether protopine derived from Hypecoum erectum L could suppress lipopolysaccharide (LPS)-induced inflammatory responses in murine macrophages (Raw 264.7 cells). Protopine was found to reduce nitric oxide (NO), cyclooxygenase-2 (COX-2), and prostaglandin E(2) (PGE(2)) production by LPS-stimulated Raw 264.7 cells, without a cytotoxic effect. Pre-treatment of Raw 264.7 cells with protopine reduced the production of pro-inflammatory cytokines. These inhibitory effects were caused by blocking phosphorylation of mitogen-activated protein kinases (MAP kinases) and also blocking activation of a nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB).
Assuntos
Benzofenantridinas/farmacologia , Alcaloides de Berberina/farmacologia , Inflamação/metabolismo , Animais , Benzofenantridinas/química , Alcaloides de Berberina/química , Linhagem Celular , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Dinoprostona/metabolismo , Lipopolissacarídeos/toxicidade , Macrófagos/efeitos dos fármacos , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Papaveraceae/química , FosforilaçãoRESUMO
Schiandra chinensis is a well-known Chinese traditional medicine for the treatment of hepatic disease. In this study, we investigated whether the nine major compounds of Schiandra chinensis could be applied to suppress lipopolysaccharide (LPS)-induced inflammatory responses in murine macrophages (Raw 264.7 cells). Among the nine lignans, three, gomisin J, gomisin N, and schisandrin C, were found to reduce nitric oxide (NO) production from LPS-stimulated Raw 264.7 cells. These three lignans showed low cytotoxic effects in Raw 264.7 cells. Pre-treatment of Raw 264.7 cells with gomisin J, gomisin N, or schisandrin C reduced the expression of mRNA and the secretion of pro-inflammatory cytokines. These inhibitory effects were found to be caused by blockage of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases 1 and 2 (ERK 1/2), and c-Jun N-terminal kinase (JNK) phosphorylation.
