RESUMO
Interleukin (IL)-23 is an essential cytokine involved in expansion of the Th17 lineage, which is associated with many immune-related destructive tissue diseases. We hypothesized that the IL-23-induced Th17 pathway plays a role in periodontal pathology and examined the expression of cytokines, and related molecules, in periodontal lesions and control sites. IL-23 and IL-12 were expressed at significantly higher levels in periodontal lesions than in control sites. However, the relative expression of the IL-23 receptor compared with the IL-12 receptor beta2 was significantly higher in periodontal lesions. Moreover, IL-17 expression was significantly higher in periodontal lesions, especially in the tissue adjacent to bone destruction, than in control sites. There was no significant difference in the expression levels of IFN-gamma, an important cytokine inhibiting differentiation toward the Th17 pathway, between periodontal lesions and control sites. Together, these results suggest that the IL-23-induced Th17 pathway is stimulated in inflammatory periodontal lesions.
Assuntos
Linfócitos T CD4-Positivos/metabolismo , Periodontite Crônica/imunologia , Periodontite Crônica/metabolismo , Interleucina-17/biossíntese , Interleucina-23/biossíntese , Estudos de Casos e Controles , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Interferon gama/biossíntese , Interleucina-12/biossíntese , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Receptores de Interleucina/biossíntese , Receptores de Interleucina-12/biossínteseRESUMO
Temperature is a critical modulator of animal metabolism and behavior, yet the mechanisms underlying the development and function of thermosensory neurons are poorly understood. C. elegans senses temperature using the AFD thermosensory neurons. Mutations in the gene ttx-1 affect AFD neuron function. Here, we show that ttx-1 regulates all differentiated characteristics of the AFD neurons. ttx-1 mutants are defective in a thermotactic behavior and exhibit deregulated thermosensory inputs into a neuroendocrine signaling pathway. ttx-1 encodes a member of the conserved OTD/OTX homeodomain protein family and is expressed in the AFD neurons. Misexpression of ttx-1 converts other sensory neurons to an AFD-like fate. Our results extend a previously noted conservation of developmental mechanisms between the thermosensory circuit in C. elegans and the vertebrate photosensory circuit, suggesting an evolutionary link between thermosensation and phototransduction.
Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans/citologia , Proteínas de Helminto/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Neurônios Aferentes/citologia , Sensação Térmica/fisiologia , Sequência de Aminoácidos , Animais , Animais Geneticamente Modificados , Comportamento Animal , Caenorhabditis elegans/genética , Caenorhabditis elegans/fisiologia , Diferenciação Celular , Linhagem da Célula , Cílios/ultraestrutura , Proteínas de Drosophila , Evolução Molecular , Regulação da Expressão Gênica no Desenvolvimento , Genes de Helmintos , Genes Homeobox , Teste de Complementação Genética , Proteínas de Helminto/química , Proteínas de Helminto/genética , Proteínas de Homeodomínio/química , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/fisiologia , Camundongos , Dados de Sequência Molecular , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/genética , Neurônios Aferentes/fisiologia , Neuropeptídeos/genética , Neuropeptídeos/fisiologia , Fatores de Transcrição Otx , Fenótipo , Células Fotorreceptoras de Vertebrados/metabolismo , Ratos , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Transdução de Sinais/fisiologia , Especificidade da Espécie , Sensação Térmica/genética , Vertebrados/genética , Vertebrados/fisiologiaRESUMO
BACKGROUND: Cellular proliferation in normal cells is tightly regulated by environmental conditions. Growth factors stimulate proliferation while cell confluence inhibits it. Human pancreatic cancer AsPC-1 cells were believed to escape from these restrictions because they possessed several mutations which promote cell proliferation. In this study, we focused on the relationships between growth conditions and the proliferation of AsPC-1 cells. MATERIALS AND METHODS: AsPC-1 cells were cultured under several growth conditions and the proliferation of cells was studied by incorporation of 3H-thymidine. The alterations of cell-cycle-related genes were studied by immunoblotting. RESULTS: By four consecutive days in culture, the nucleotide incorporation of AsPC-1 cells was markedly suppressed and the suppression was overcome by medium change or reduction of cell density. The induction of cyclin D1 by serum stimulation was observed, concomitant with the transient activation of extracellular signal-regulated kinases (ERKs). The most prominent changes of cell-cycle-regulating genes following consecutive culture or serum reduction were the down-regulation of cyclin E and the induction of p27KIP1. The down-regulation of cyclin E was more sensitive to cell density, while the induction of p27KIP1 was regulated by both increased cell density and reduction of serum. The down-regulation of p27KIP1 was caused by protein degradation. CONCLUSIONS: The proliferation of AsPC-1 cells was still controlled by cell density and serum stimulation; nevertheless, the cells possessed several oncogenic mutations. These results may provide a rationale for modifying the growth environment for treatment of pancreatic cancers.
Assuntos
Proteínas de Ciclo Celular/biossíntese , Ciclina E/biossíntese , Neoplasias Pancreáticas/metabolismo , Proteínas Supressoras de Tumor , Adenocarcinoma/metabolismo , Divisão Celular , Linhagem Celular , Meios de Cultura/farmacologia , Inibidor de Quinase Dependente de Ciclina p27 , Regulação para Baixo , Immunoblotting , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Neoplasias Pancreáticas/genética , Fosforilação , Fatores de Tempo , Células Tumorais CultivadasRESUMO
On a radial temperature gradient, C. elegans worms migrate, after conditioning with food, toward their cultivation temperature and move along this isotherm. This experience-dependent behavior is called isothermal tracking (IT). Here we show that the neuron-specific calcium sensor-1 (NCS-1) is essential for optimal IT. ncs-1 knockout animals show major defects in IT behavior, although their chemotactic, locomotor, and thermal avoidance behaviors are normal. The knockout phenotype can be rescued by reintroducing wild-type NCS-1 into the AIY interneuron, a key component of the thermotaxis network. A loss-of-function form of NCS-1 incapable of binding calcium does not restore IT, whereas NCS-1 overexpression enhances IT performance levels, accelerates learning (faster acquisition), and produces a memory with slower extinction. Thus, proper calcium signaling via NCS-1 defines a novel pathway essential for associative learning and memory.
Assuntos
Caenorhabditis elegans/metabolismo , Sinalização do Cálcio/fisiologia , Proteínas de Ligação ao Cálcio/metabolismo , Aprendizagem/fisiologia , Memória/fisiologia , Sistema Nervoso/metabolismo , Neurônios/metabolismo , Neuropeptídeos/metabolismo , Animais , Comportamento Animal/fisiologia , Caenorhabditis elegans/citologia , Proteínas de Ligação ao Cálcio/genética , Comportamento Alimentar/fisiologia , Regulação da Expressão Gênica/fisiologia , Mutação/fisiologia , Sistema Nervoso/citologia , Vias Neurais/citologia , Vias Neurais/metabolismo , Proteínas Sensoras de Cálcio Neuronal , Neurônios/citologia , Neuropeptídeos/genética , Transmissão Sináptica/fisiologia , Sensação Térmica/genéticaRESUMO
We report a case of pelvic recurrence of advanced rectal carcinoma, presenting a favorable response with a low dose (25 mg/m2) of CPT-11 (Irinotecan) combined with topical hyperthermia for relapse after treatment with 4 cycles of high-dose (100 mg/m2) CPT-11 chemotherapy alone. This combination therapy was safely carried out on an outpatient basis. The degrees of recovery of the left lower limb pain and edema, and of serum CEA reduction were comparable to those in high-dose chemotherapy alone. No significant adverse effects were encountered in the thermo-chemotherapy attempted. Since hyperthermic treatment enhances the cytotoxic effects of CPT-11 in vitro, topical hyperthermia with low-dose CPT-11 therapy may produce a response comparable to that in high-dose CPT-11 chemotherapy alone. However, an optimal dose and comparative study with other chemotherapeutic agents would be needed. This regimen may be advantageous in the maintenance of quality of life for the palliation of postoperative pelvic recurrence since this treatment can be performed on an outpatient basis.
Assuntos
Adenocarcinoma/terapia , Antineoplásicos Fitogênicos/administração & dosagem , Camptotecina/análogos & derivados , Hipertermia Induzida , Neoplasias Pélvicas/terapia , Neoplasias Retais/terapia , Adenocarcinoma/secundário , Camptotecina/administração & dosagem , Terapia Combinada , Esquema de Medicação , Feminino , Humanos , Irinotecano , Pessoa de Meia-Idade , Neoplasias Pélvicas/secundárioRESUMO
The uteri of mice up to 20 days after birth show estrogen-independent growth, although their growth is accelerated by estrogen, while the growth of the uteri of mice after 20 days completely depends on estrogen. In the present study, we compared the sensitivities of uterine cells in their proliferation responding to epidermal growth factor (EGF) and diethylstilbestrol (DES) between 5-day-old and 25-day-old ovariectomized mice. A single subcutaneous injection of EGF at doses of 0.25 and over 0.25 microgram/g body weight (BW) increased 3H-thymidine uptake by the whole uterus dose-dependently in both 25-day-old and 5-day-old mice, and a maximal increase in the 3H-thymidine uptake was attained at a dose of 1 microgram/g BW of EGF in both mice. A single subcutaneous injection of DES at 0.001 and over 0.001 microgram/g BW increased 3H-thymidine uptake by the whole uterus dose-dependently in both 25-day-old and 5-day-old mice, and a maximal increase was attained at 0.004 microgram/g BW of DES in both mice. EGF and DES increased labeling indices of both the epithelium and stroma in both 25-day-old and 5-day-old mice. The present results suggest that sensitivities of uterine cells of neonatal mice in their proliferation responding to EGF and DES are similar to those of postneonatal mice.