RESUMO
We performed a comparative in vitro study of the involvement of NF-κB, PI3K, cAMP, ERK1/2, p38, JAKs, STAT3, JNK, and p53-dependent intracellular signaling in the functioning of neural stem cells (NSC) under the influence of basic fibroblast growth factor (FGF) and FGF receptor agonist, diterpene alkaloid songorine. The significant differences in FGFR-mediated intracellular signaling in NSC were revealed for these ligands. In both cases, stimulation of progenitor cell proliferation occurs with the participation of NF-κB, PI3K, ERK1/2, JAKs, and STAT3, while JNK and p53, on the contrary, inhibit cell cycle progression. However, under the influence of songorin, cAMP- and p38-mediated cascades are additionally involved in the transmission of the NSC division-activating signal. In addition, unlike FGF, the alkaloid stimulates progenitor cell differentiation by activating ERK1/2, p38, JNK, p53, and STAT3.
Assuntos
Diferenciação Celular , Proliferação de Células , Diterpenos , Células-Tronco Neurais , Receptores de Fatores de Crescimento de Fibroblastos , Fator de Transcrição STAT3 , Transdução de Sinais , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/citologia , Animais , Fator de Transcrição STAT3/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/agonistas , Transdução de Sinais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Diterpenos/farmacologia , Diferenciação Celular/efeitos dos fármacos , NF-kappa B/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Fator 2 de Crescimento de Fibroblastos/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/agonistas , Fosfatidilinositol 3-Quinases/metabolismo , Alcaloides/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Janus Quinases/metabolismo , AMP Cíclico/metabolismo , Células Cultivadas , RatosRESUMO
We studied the involvement of cAMP and PKA in the regulation of the secretion of neurotrophic growth factors by macro-and microglial cells in the model of ethanol-induced neurodegeneration in vitro and in vivo. The stimulating role of cAMP in the secretion of neurotrophins by intact astrocytes and oligodendrocytes was shown, while PKA does not participate in this process. On the contrary, the inhibitory role of cAMP (implemented via PKA activation) in the production of neurogenesis stimulators by microglial cells under conditions of optimal vital activity was found. Under the influence of ethanol, the role of cAMP and PKA in the production of growth factors by macroglial cells was considerably changed. The involvement of PKA in the cAMP-dependent signaling pathways and inversion of the role of this signaling pathway in the implementation of the neurotrophic secretory function of astrocytes and oligodendrocytes, respectively, directly exposed to ethanol in vitro were noted. Long-term exposure of the nervous tissue to ethanol in vivo led to the loss of the stimulating role of cAMP/PKA signaling on neurotrophin secretion by macroglial cells without affecting its inhibitory role in the regulation of this function in microglial cells.
Assuntos
Proteínas Quinases Dependentes de AMP Cíclico , Etanol , Etanol/toxicidade , Proteínas Quinases Dependentes de AMP Cíclico/genética , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , AMP Cíclico/metabolismo , Transdução de Sinais , Astrócitos/metabolismoRESUMO
Under conditions of steady-state hemopoiesis, nuclear factor NF-κB, in contrast to MAP kinase p38, plays an important role in the maintenance of the initial level of secretory activity of monocytes. The increase in the production of G-CSF under stress conditions (10-h immobilization) is mainly regulated by the alternative p38MARK signaling pathway via activation of p38 synthesis. It was shown that under conditions of cytostatic-induced myelosuppression, the production of protein kinase p38 in cells decreases, and it, like NF-κB, is not the main one in the production of hemopoietin by mononuclear phagocytes.
Assuntos
Diferenciação Celular , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Fagócitos/fisiologia , Animais , Células da Medula Óssea/fisiologia , Fator Estimulador de Colônias de Granulócitos/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/fisiologia , NF-kappa B/metabolismo , Fagócitos/metabolismo , Transdução de Sinais/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
We studied the participation of JNK and p53 in the realization of the growth potential of different types of progenitors of the subventricular zone of mouse brain and secretion of neurotrophins by glial cells. The stimulating role of these signaling molecules in mitotic activity and specialization of multipotent neural stem cells was shown. It was found that JNK and p53 do not participate in the regulation of committed neuronal progenitor cells (clonogenic PSA-NCAM+ cells). A dependence of neurotrophic growth factors in individual populations of neuroglia on activity of these protein kinase and transcription factor was revealed. The role of JNK and p53 in astrocytes consists in stimulation of their secretion, and in microglial cells, on the contrary, in its inhibition. The secretory neurotrophic function of oligodendrogliocytes is not associated with JNK and p53 activity.
Assuntos
Astrócitos/metabolismo , MAP Quinase Quinase 4/genética , Células-Tronco Multipotentes/metabolismo , Células-Tronco Neurais/metabolismo , Neuroglia/metabolismo , Proteína Supressora de Tumor p53/genética , Animais , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Benzotiazóis/farmacologia , Antígeno CD56/genética , Antígeno CD56/metabolismo , Meios de Cultivo Condicionados/farmacologia , Regulação da Expressão Gênica , Ventrículos Laterais/citologia , Ventrículos Laterais/efeitos dos fármacos , Ventrículos Laterais/metabolismo , MAP Quinase Quinase 4/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Multipotentes/citologia , Células-Tronco Multipotentes/efeitos dos fármacos , Fatores de Crescimento Neural/biossíntese , Fatores de Crescimento Neural/genética , Moléculas de Adesão de Célula Nervosa/genética , Moléculas de Adesão de Célula Nervosa/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/efeitos dos fármacos , Neuroglia/citologia , Neuroglia/efeitos dos fármacos , Transdução de Sinais , Tolueno/análogos & derivados , Tolueno/farmacologia , Proteína Supressora de Tumor p53/metabolismoRESUMO
Humic acids extracted with sodium pyrophosphate from Oligotrophic Sphagnum magellanicum peat reduce mitogen-stimulated production of anti-inflammatory cytokine IL-10 by mouse peritoneal macrophages and do not affect the secretion of IL-4 by lymphocytes. The studied humic acid sample stimulates the production of proinflammatory cytokines IL-12, TNFα, IL-1ß, and IFNγ by immunocompetent mouse cells and human mononuclear cells. Course administration of humic acids to mice enhances the humoral immunity, increasing the number of antibody-forming cells in the spleen and the titer of antibodies in the blood serum after immunization with sheep red blood cells.
Assuntos
Substâncias Húmicas , Solo , Animais , Interleucina-12/metabolismo , Interleucina-1beta/metabolismo , Macrófagos Peritoneais/metabolismo , Camundongos Endogâmicos C57BL , Sphagnopsida/química , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The hemostimulating effects of c-Jun N-terminal kinase (JNK) inhibitor were examined on the mouse model of myelosuppression provoked by 5-fluorouracil. Blockade of JNK during postcytostatic period accelerated recovery of granulomonocytopoiesis and erythropoiesis. It also increased the content of neutrophilic granulocytes and erythroid cells in the hematopoietic tissue and elevated the counts of neutrophils and reticulocytes in the peripheral blood. The development of these phenomena resulted from elevated content and up-regulated functional activity of bone marrow hematopoietic progenitors associated with the direct action of JNK inhibitor on these progenitors and enhanced secretion of hemopoietins by stromal elements of the hematopoiesis-inducing microenvironment.
Assuntos
Citostáticos/farmacologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Animais , Células Eritroides/efeitos dos fármacos , Células Eritroides/metabolismo , Fluoruracila/farmacologia , Granulócitos/efeitos dos fármacos , Granulócitos/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Reticulócitos/efeitos dos fármacos , Reticulócitos/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
The role of JAK/STAT3-mediated signaling pathway in the realization of the growth potential of mesenchymal precursor cells was examined in vitro. The stimulating role of JAKs and STAT3 towards proliferating activity of progenitor cells and their different role in the regulation of differentiation of the progenitor elements were demonstrated. Inhibitors of JAKs and STAT3 reduced the yield of fibroblast CFU and their mitotic activity. Blockade of JAKs accelerated and selective inactivation of STAT3 decelerated differentiation of progenitor cells.
Assuntos
Células da Medula Óssea/metabolismo , Fibroblastos/metabolismo , Janus Quinase 1/genética , Janus Quinase 3/genética , Células-Tronco Mesenquimais/metabolismo , Fator de Transcrição STAT3/genética , Animais , Antraquinonas/farmacologia , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Regulação da Expressão Gênica , Janus Quinase 1/antagonistas & inibidores , Janus Quinase 1/metabolismo , Janus Quinase 3/antagonistas & inibidores , Janus Quinase 3/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Nitrilas , Fosforilação , Cultura Primária de Células , Pirazóis/farmacologia , Pirimidinas , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Sulfonamidas/farmacologiaRESUMO
Involvement of individual JAK kinases in the realization of growth potential of mesenchymal progenitor cells was examined in vitro. Important role of JAK2 and JAK3 in determining the initial level of mitotic activity of progenitor cells was established. The yield of fibroblast CFUF was suppressed under the effect of specific inhibitors of JAK kinases. Blockade of JAK3 increased the rate of progenitor element differentiation. JAK1 had no effect on proliferation and differentiation status of progenitor cells.
Assuntos
Diferenciação Celular , Proliferação de Células , Janus Quinases/fisiologia , Células-Tronco Mesenquimais/enzimologia , Animais , Células Cultivadas , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos Endogâmicos CBARESUMO
Screening study of the effects of sweet flag (Acorus calamus L.) rhizome and clover (Trifolium pratense L.) aerial part on the production of NO by mouse macrophages was carried out. The polysaccharides were separated by ion exchange chromatography into fractions differing by monomeric composition and ramification type and were used in concentrations of 20, 40, and 100 µg/ml. Four fractions of Acorus calamus L. (PSF-101, PSF-102, PSF-103, and PSF-105), used in different concentrations, moderately stimulated nitrite production by macrophages. Three of five Trifolium pratense L. polysaccharides (PS62-3, PS62-4, and PS62-5) exhibited a significant specific effect on NO production. Rhamnogalactouronans from clover PS63-3 in all concentrations and from PS62-5 in a concentration of 100 µg/ml exhibited the highest activity, comparable to the NO-stimulatory activity of the reference LPS, while polysaccharide PS62-3 in a concentration of 40 µg/ml exhibited even higher activity.
Assuntos
Acorus/química , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Óxido Nítrico/metabolismo , Pectinas/farmacologia , Polissacarídeos/farmacologia , Trifolium/química , Animais , Células Cultivadas , Feminino , Masculino , Camundongos , Pectinas/química , Polissacarídeos/químicaRESUMO
The role of JNK-mediated signal pathway and participation of p53 transcription factor in stimulation of mesenchymal precursor cell function by the fibroblast growth factor was studied. The levels of fibroblast colony- and cluster formation and proliferative activity of mesenchymal precursors increased in response to JNK and p53 specific inhibitors. JNK and p53 blockers did not change the rate of fibroblast growth factor-induced progenitor element differentiation.
Assuntos
Fatores de Crescimento de Fibroblastos/fisiologia , MAP Quinase Quinase 4/metabolismo , Células-Tronco Mesenquimais/fisiologia , Proteína Supressora de Tumor p53/fisiologia , Animais , Proliferação de Células , Células Cultivadas , Masculino , Camundongos Endogâmicos CBA , Transdução de SinaisRESUMO
We studied the role of intracellular signaling molecules PI3K, ÐÐÐ K ERK1/2, and Ñ38 in stimulation of realization of the growth potential of mesenchymal progenitor cells by alkaloid songorine in vitro. Inhibitors of PI3K, ERK1/2 and Ñ38 canceled the increase in proliferative activity of progenitor cells, the blockers of ERK1/2 and Ñ38 reduced the intensity of progenitor cell differentiation.
Assuntos
Alcaloides/farmacologia , Sistema de Sinalização das MAP Quinases/fisiologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/enzimologia , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Cromonas/farmacologia , Ensaio de Unidades Formadoras de Colônias , Flavonoides/farmacologia , Imidazóis/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células-Tronco Mesenquimais/enzimologia , Camundongos , Camundongos Endogâmicos CBA , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/fisiologia , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/fisiologia , Modelos Biológicos , Morfolinas/farmacologia , Fosfatidilinositol 3-Quinases/fisiologia , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/fisiologiaRESUMO
Specific JNK and p53 inhibitors stimulated the formation of fibroblast colonies (CFU-F) and clusters (ClFU-F) and increased proliferative activity of mesenchymal progenitor cells. No effects of inhibitors of JNK and p53 on differentiation of progenitor elements were revealed.
Assuntos
Benzotiazóis/farmacologia , Proliferação de Células/fisiologia , MAP Quinase Quinase 4/antagonistas & inibidores , Células-Tronco Mesenquimais/fisiologia , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais/fisiologia , Tolueno/análogos & derivados , Proteína Supressora de Tumor p53/antagonistas & inibidores , Animais , Proliferação de Células/efeitos dos fármacos , Hidroxiureia , Técnicas In Vitro , Masculino , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos CBA , Estatísticas não Paramétricas , Tolueno/farmacologiaRESUMO
We studied the role of NF-κB/IKK-mediated signaling in the stimulation of growth potential of mesenchymal progenitor cells by alkaloid songorine in vitro. Specific NF-κB inhibitor oridonin abolished activation of proliferation and differentiation of progenitor cells. Aurothiomalate, a selective blocker of IKK-2, also suppressed mitotic activity of fibroblast precursors, but had no effect on the rate of the differentiation.
Assuntos
Alcaloides/farmacologia , Quinase I-kappa B/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , NF-kappa B/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Diterpenos do Tipo Caurano/farmacologia , Tiomalato Sódico de Ouro/farmacologia , Quinase I-kappa B/antagonistas & inibidores , Camundongos , Modelos Biológicos , NF-kappa B/antagonistas & inibidores , Medicina RegenerativaRESUMO
We studied PI3K, MAPK/EPK1/2 and p38-dependent signaling cascade under stimulation of the functions of mesenchymal progenitor cells by fibroblast growth factor. The important role of PI3K and EPK1/2 in the realization of their growth potential has been revealed. Experiments have demonstrated a blocking effect of PI3K inhibitor on proliferation and differentiation of progenitor cells and EPK1/2 inhibitor on mitotic activity of the progenitor cells. The p38-mediated MAPK pathway did not play a role in determining the proliferative and differentiation status of fibroblast CFU.
Assuntos
Fator 2 de Crescimento de Fibroblastos/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação da Expressão Gênica , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos CBA , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Cultura Primária de Células , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
We studied the in vitro role of NF-κB-dependent signaling in the growth capacity of mesenchymal progenitor cells upon stimulation by basic fibroblast growth factor. Proliferative activity of progenitor cells was suppressed by specifi c inhibitors of this transcription factor (NF-κB), oridonin and aurothiomalate. These inhibitors had no effect on differentiation of fibroblast CFU.
Assuntos
Fator 2 de Crescimento de Fibroblastos/fisiologia , Células-Tronco Mesenquimais/fisiologia , NF-kappa B/metabolismo , Animais , Pontos de Checagem do Ciclo Celular , Proliferação de Células , Células Cultivadas , Camundongos Endogâmicos CBA , Sistemas do Segundo MensageiroRESUMO
We studied the role of cAMP- and IKK-2-dependent pathways under conditions of functional stimulation of mesenchymal progenitor cells by basic fibroblast growth factor. An adenylate cyclase inhibitor 2',5'-dideoxyadenosine had no effect on functional activity of early (primitive) mesenchymal precursors. This agent produced a stimulatory effect on proliferation of stromal precursor cells. Mitotic activity of mesenchymal progenitor cells was shown to decrease after treatment with a specific blocker of the IKK-2 kinase-inhibitor complex.
Assuntos
AMP Cíclico/metabolismo , Fator 2 de Crescimento de Fibroblastos/farmacologia , Quinase I-kappa B/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Transdução de Sinais/fisiologia , Animais , Células Cultivadas , Células-Tronco Mesenquimais/citologia , Camundongos , Medicina RegenerativaRESUMO
We studied the mechanisms of regenerative (wound healing) effects of songorine associated with functional activation of mesenchymal progenitor cells. The key role of FGF receptors on these progenitor cells in the stimulation of realization of their growth potential under the effect of the alkaloid was demonstrated. Under in vitro conditions, the antibodies to FGF receptor abolished the songorine-induced increase in the number of fibroblast colony-forming units in bone marrow cell culture. The intensity of differentiation of mesenchymal precursors remained unchanged.
Assuntos
Aconitum/química , Alcaloides/farmacologia , Receptores de Fatores de Crescimento de Fibroblastos/genética , Pele/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Ferimentos não Penetrantes/tratamento farmacológico , Alcaloides/isolamento & purificação , Animais , Animais não Endogâmicos , Anticorpos/farmacologia , Células Cultivadas , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Expressão Gênica , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Receptores de Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais , Pele/lesões , Pele/metabolismo , Cicatrização/genética , Ferimentos não Penetrantes/metabolismo , Ferimentos não Penetrantes/patologiaRESUMO
The study examines the role of signal pathways in triggering the compensatory reactions in the blood system in response to the cytostatic administration. In vitro experiments elucidated the involvement of protein kinase p38 in the synthesis of granulocytic CSF by cells of hemopoietic microenvironment. The important role of the transcriptional factor NF-κB and protein kinase p38 in limitation of the processes of maturation of the hemopoietic precursors was demonstrated.
Assuntos
Células da Medula Óssea/metabolismo , Ciclofosfamida/farmacologia , Agonistas Mieloablativos/farmacologia , NF-kappa B/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/patologia , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Células Eritroides/efeitos dos fármacos , Células Eritroides/metabolismo , Células Eritroides/patologia , Regulação da Expressão Gênica , Tiomalato Sódico de Ouro/farmacologia , Fator Estimulador de Colônias de Granulócitos/biossíntese , Fator Estimulador de Colônias de Granulócitos/metabolismo , Granulócitos/efeitos dos fármacos , Granulócitos/metabolismo , Granulócitos/patologia , Hematopoese/efeitos dos fármacos , Imidazóis/farmacologia , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos CBA , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , Cultura Primária de Células , Piridinas/farmacologia , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/genéticaRESUMO
We studied the effect of two pectic polysaccharides PS-B1-AG and PS-B2-RG that were contained in total polysaccharides extracted from Betula pendula leaves on NO production by mouse macrophages and the contribution of signaling molecules to macrophage activation by the test substances. Unlike the total sample, pectins produced a NO-stimulating effect on macrophages. The effect of PS-B2-RG (10 µg/ml) did not differ from the effect of LPS, while PS-B1-AG produced this effect only in a concentration of 20 µg/ml, which was probably due to differences in the chemical structure of the test substances. The studied pectin polysaccharides activated transcription factor NF-κB, kinases p38 and PI3, and cAMP as a negative regulator. These results indicate that Betula pendula polysaccharides are promising substances for creation of immunomodulating drugs.
Assuntos
Betula/química , Fatores Imunológicos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Polissacarídeos/farmacologia , Animais , Células Cultivadas , AMP Cíclico/metabolismo , Feminino , Lipopolissacarídeos/farmacologia , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Óxido Nítrico/biossíntese , Fosfatidilinositol 3-Quinases/metabolismo , Folhas de Planta/química , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
We studied the role of intracellular signal molecules PI3K, MAPK ERK1/2, and p38 in the realization of the growth potential of mesenchymal progenitor elements. Under in vitro conditions, PI3K и ERK1/2 specifi c inhibitors reduced fi broblastic colony- and cluster-formation and considerably suppressed proliferative activity of mesenchymal precursors. Blocker of p38 and protein kinase B had no effect on the function of fi broblast CFU.