ABSTRACT
Fatores produzidos no ovário como os membros da família dos fatores de crescimento transformantes beta (TGFβ) e seus receptores, são essenciais durante o desenvolvimento folicular. Membros desta superfamília desempenham papel chave na fertilidade e diferenças espécie-específicas na regulação desses fatores têm sido descritas, envolvendo as funções ovarianas em condições fisiológicas ou patológicas. A proteína morfogenética óssea 15 (BMP15) e o fator de crescimento e diferenciação 9 (GDF9) destacam-se, pois desempenham papéis importantes na regulação do crescimento e da diferenciação folicular. Ainda, há evidências de que outras BMPs, ativinas, inibinas e seus receptores também possam estar envolvidos no controle da foliculogênese, ovulação/luteinização e luteólise. A maioria dos dados demostram que os TGFs atuam regulando negativamente a síntese de progesterona, o que sugere envolvimento na inibição da luteinização e promoção da luteólise. O avanço no entendimento das funções destes fatores locais poderá possibilitar o desenvolvimento tanto de novas estratégias contraceptivas, como também para controle do ciclo estral ou menstrual.
Factors produced in the ovary, such as transforming growth factors beta members (TGFβ) and their receptors, play a key role during follicular development. Members from this family have an important role in female fertility and species-specific differences in their regulation have been described, being involved in ovarian function regulation under both physiological and pathological conditions. Bone morphogenetic protein 15 (BMP15) and growth and differentiation factor 9 (GDF9) are the most studied factors due to their involvement in the regulation of follicular development and differentiation. Besides BMP15 and GDF9, other BMPs, activins, inhibins and their receptors may be involved in the control of folliculogenesis, ovulation/luteinization and luteolysis. Most studies demonstrate that TGFβ members negatively regulate progesterone synthesis, suggesting an involvement in luteolysis. The advance in the knowledge of the function of these local factors may allow the development of new contraceptive strategies as well as new approaches to control the estrous or menstrual cycle.
Subject(s)
Female , Animals , Transforming Growth Factors/analysis , Transforming Growth Factors/biosynthesis , Luteinization , LuteolysisABSTRACT
Fatores produzidos no ovário como os membros da família dos fatores de crescimento transformantes beta (TGFβ) e seus receptores, são essenciais durante o desenvolvimento folicular. Membros desta superfamília desempenham papel chave na fertilidade e diferenças espécie-específicas na regulação desses fatores têm sido descritas, envolvendo as funções ovarianas em condições fisiológicas ou patológicas. A proteína morfogenética óssea 15 (BMP15) e o fator de crescimento e diferenciação 9 (GDF9) destacam-se, pois desempenham papéis importantes na regulação do crescimento e da diferenciação folicular. Ainda, há evidências de que outras BMPs, ativinas, inibinas e seus receptores também possam estar envolvidos no controle da foliculogênese, ovulação/luteinização e luteólise. A maioria dos dados demostram que os TGFs atuam regulando negativamente a síntese de progesterona, o que sugere envolvimento na inibição da luteinização e promoção da luteólise. O avanço no entendimento das funções destes fatores locais poderá possibilitar o desenvolvimento tanto de novas estratégias contraceptivas, como também para controle do ciclo estral ou menstrual.(AU)
Factors produced in the ovary, such as transforming growth factors beta members (TGFβ) and their receptors, play a key role during follicular development. Members from this family have an important role in female fertility and species-specific differences in their regulation have been described, being involved in ovarian function regulation under both physiological and pathological conditions. Bone morphogenetic protein 15 (BMP15) and growth and differentiation factor 9 (GDF9) are the most studied factors due to their involvement in the regulation of follicular development and differentiation. Besides BMP15 and GDF9, other BMPs, activins, inhibins and their receptors may be involved in the control of folliculogenesis, ovulation/luteinization and luteolysis. Most studies demonstrate that TGFβ members negatively regulate progesterone synthesis, suggesting an involvement in luteolysis. The advance in the knowledge of the function of these local factors may allow the development of new contraceptive strategies as well as new approaches to control the estrous or menstrual cycle.(AU)
Subject(s)
Animals , Female , Luteinization , Luteolysis , Transforming Growth Factors/analysis , Transforming Growth Factors/biosynthesisABSTRACT
OBJECTIVE: In this study, we evaluated whether budlein A modulates the activation of innate and adaptive immune cells such as neutrophils and lymphocytes. MATERIAL AND METHODS: Our research group has investigated several plant species and several compounds have been isolated, identified, and their medical potential evaluated. Budlein A is a SL isolated from the species Aldama buddlejiformis and A. robusta (Asteraceae) and shows anti-inflammatory and anti-nociceptive activities. Advances in understanding how plant-derived substances modulate the activation of innate and adaptive immune cells have led to the development of new therapies for human diseases. RESULTS: Budlein A inhibited MPO activity, IL-6, CXCL8, IL-10, and IL-12 production and induces neutrophil apoptosis. In contrast, budlein A inhibited lymphocyte proliferation and IL-2, IL-10, TGF-ß, and IFN-γ production, but it did not lead to cell death. CONCLUSIONS: Collectively, our results indicate that budlein A shows distinct immunomodulatory effects on immune cells.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Lactones/pharmacology , Neutrophils/drug effects , Sesquiterpenes/pharmacology , T-Lymphocytes/drug effects , Adult , Analysis of Variance , Apoptosis/drug effects , Asteraceae/chemistry , Cell Proliferation/drug effects , Cells, Cultured , Enzyme-Linked Immunosorbent Assay , Female , Flow Cytometry , Humans , Interleukin-8/analysis , Interleukin-8/drug effects , Interleukins/analysis , Male , Middle Aged , Peroxidase/analysis , Peroxidase/drug effects , Reproducibility of Results , Transforming Growth Factors/analysis , Transforming Growth Factors/drug effectsABSTRACT
ABSTRACT Sesquiterpene lactones (SLs) are the active constituents of a variety of medicinal plants used in traditional medicine for the treatment of inflammatory diseases and other ailments. Objective In this study, we evaluated whether budlein A modulates the activation of innate and adaptive immune cells such as neutrophils and lymphocytes. Material and Methods Our research group has investigated several plant species and several compounds have been isolated, identified, and their medical potential evaluated. Budlein A is a SL isolated from the species Aldama buddlejiformis and A. robusta (Asteraceae) and shows anti-inflammatory and anti-nociceptive activities. Advances in understanding how plant-derived substances modulate the activation of innate and adaptive immune cells have led to the development of new therapies for human diseases. Results Budlein A inhibited MPO activity, IL-6, CXCL8, IL-10, and IL-12 production and induces neutrophil apoptosis. In contrast, budlein A inhibited lymphocyte proliferation and IL-2, IL-10, TGF-β, and IFN-γ production, but it did not lead to cell death. Conclusions Collectively, our results indicate that budlein A shows distinct immunomodulatory effects on immune cells.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Sesquiterpenes/pharmacology , T-Lymphocytes/drug effects , Lactones/pharmacology , Anti-Inflammatory Agents/pharmacology , Neutrophils/drug effects , Enzyme-Linked Immunosorbent Assay , Transforming Growth Factors/analysis , Transforming Growth Factors/drug effects , Cells, Cultured , Reproducibility of Results , Analysis of Variance , Interleukin-8/analysis , Interleukin-8/drug effects , Interleukins/analysis , Apoptosis/drug effects , Peroxidase/analysis , Peroxidase/drug effects , Asteraceae/chemistry , Cell Proliferation/drug effects , Flow CytometryABSTRACT
INTRODUCTION: Severe odontogenic infections remain an important public health concern and a significant economic burden to public health care facilities. Despite this, several aspects of the disease, such as its immune response profile, remain poorly understood. The aim of this study was to search for an association between mRNA levels of the cytokines interferon-γ, interleukin (IL)-1ß, tumor necrosis factor-α, IL-17A, IL-10, and transforming growth factor-ß and the chemokines IL-8, CCL2/MCP-1, and CCL5 and odontogenic infection. METHODS: The case group was composed of 12 patients hospitalized in consequence of severe odontogenic infection, and our control group included 12 individuals with healthy periapical tissues. Clinical samples were taken from the case (drainage site) and control (periapical interstitial fluid) groups with the aid of paper points. Total RNA was extracted, complementary DNA was synthesized, and mRNA levels were determined by quantitative polymerase chain reaction. Data analysis was performed by using SPSS, and the Wilcoxon signed rank test was used to determine statistical significance (P < .05). RESULTS: Data generated showed a significantly increased expression of proinflammatory cytokines (interferon-γ, IL-1ß, tumor necrosis factor-α, and IL-17A), IL-8, and CCL2/MCP-1 in odontogenic infection patients. The mRNA levels of IL-10, transforming growth factor-ß, and CCL5 were similar in both study groups. CONCLUSIONS: In general, individuals presenting with odontogenic infections exhibited extraordinary proinflammatory cytokine profiles paralleled with unaltered expression of regulatory mediators.
Subject(s)
Cytokines/analysis , Cytokines/metabolism , Jaw Diseases/metabolism , Adolescent , Adult , Brazil , Chemokine CCL2/analysis , Chemokine CCL5/analysis , Chemokines/analysis , Female , Hospitalization , Humans , Interferon-gamma/analysis , Interleukin-10/analysis , Interleukin-17/analysis , Interleukin-1beta/analysis , Interleukin-8/analysis , Male , Middle Aged , Odontogenic Cysts , RNA, Messenger/analysis , Transforming Growth Factors/analysis , Tumor Necrosis Factor-alpha/analysis , Young AdultABSTRACT
A binding competition assay was used to measure the content of transforming growth factor alpha in human mammary carcinomas and their metastases. Thirty one percent of the primary and 50 percent of the metastases expressed the transforming growth factor alpha with values ranging between 1.6 to 278 EGF equivalent ng/mg tumour extract protein. There was no correlation between the transforming growth factor alpha content and the estrogen receptor value.