RESUMO
Epidemiological studies have associated long-term exposure to environmental air pollution particulate matter (PM) with the development of diverse health problems. They include infectious respiratory diseases related to the deregulation of some innate immune response mechanisms, such as the host defense peptides' expression. Herein, we evaluated in BALB/c mice the effect of long-standing exposure (60 days) to urban-PM from the south of Mexico City, with aerodynamic diameters below 2.5 µm (PM2.5) and 10 µm (PM10) on the lung's gene expression and production of three host defense peptides (HDPs); murine beta-defensin-3, -4 (mBD-3, mBD-4) and cathelin-related antimicrobial peptide (CRAMP). We also evaluated mRNA levels of Il1b and Il10, two cytokines related to the expression of host defense peptides. Exposure to PM2.5 and PM10 differentially induced lung inflammation, being PM2.5, which caused higher inflammation levels, probably associated with a differential deposition on the airways, that facilitate the interaction with alveolar macrophages. Inflammation levels were associated with an early upregulation of the three HDPs assessed and an increment in Il1b mRNA levels. Interestingly, after 28 days of exposure, Il10 mRNA upregulation was observed and was associated with the downregulation of HDPs and Il1b mRNA levels. The upregulation of Il10 mRNA and suppression of HDPs might facilitate microbial colonization and the development of diseases associated with long-term exposure to PM.
Assuntos
Poluentes Atmosféricos/toxicidade , Catelicidinas/metabolismo , Interleucina-1beta/metabolismo , Material Particulado/toxicidade , Pneumonia/patologia , beta-Defensinas/metabolismo , Animais , Catelicidinas/genética , Interleucina-1beta/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pneumonia/etiologia , Pneumonia/metabolismo , beta-Defensinas/genéticaRESUMO
Several studies have documented the interaction between the immune and endocrine systems as an effective defense strategy against tuberculosis, involving the production of several molecules and immunological processes. In this study, we determined the effect of cortisol and dehydroepiandrosterone (DHEA) on the production of antimicrobial peptides such as cathelicidin and human ß-defensin (HBD) -2, and HBD-3 and their effect on intracellular growth of Mycobacterium tuberculosis (Mtb) in lung epithelial cells and macrophages. Our results showed that DHEA promotes the production of these antimicrobial peptides in infected cells, correlating with the decrease of Mtb bacilli loads. These results suggest the use of exogenous DHEA as an adjuvant for tuberculosis therapy.
Assuntos
Peptídeos Catiônicos Antimicrobianos/biossíntese , Desidroepiandrosterona/farmacologia , Hidrocortisona/farmacologia , Mycobacterium tuberculosis , beta-Defensinas/biossíntese , Células A549 , Células Epiteliais/microbiologia , Humanos , Macrófagos/microbiologia , Células THP-1 , CatelicidinasRESUMO
Tuberculosis (TB) is the first cause of death by a single infectious agent. Previous reports have highlighted the presence of platelets within Tb granulomas, albeit the immune-associated platelet response to Mycobacterium tuberculosis (Mtb) has not been deeply studied. Our results showed that platelets are recruited into the granuloma in the late stages of tuberculosis. Furthermore, electron-microscopy studies showed that platelets can internalize Mtb and produce host defense peptides (HDPs), such as RNase 7, HBD2 and hPF-4 that bind to the internalized Mtb. Mtb-infected platelets exhibited higher transcription and secretion of IL-1ß and TNF-α, whereas IL-10 and IL-6 protein levels decreased. These results suggest that platelets participate in the immune response against Mtb through HDPs and cytokines production.
Assuntos
Mycobacterium tuberculosis , Tuberculose , Plaquetas , Citocinas , Granuloma , Humanos , ImunidadeRESUMO
The aim of the present work was to evaluate MTX treatment (0.1, 1 and 10 µg mL-1) in vitro in order to characterize its effects on cell proliferation alterations in cell cycle of HaCaT keratinocytes and wound healing in a Skh1 mice treated with MTX (low doses 30 mg kg-1, high doses 200 mg kg-1 and repeated doses at 1.5 mg kg-1). We analyzed the cytotoxic effect of methotrexate by a resazurin assay. The effects in the proliferation, cell cycle and apoptosis of HaCaT cells were analyzed by flow cytometry. The effects of MTX on wound healing in vivo were also analyzed. A trend toward reduction in the resazurin assay was found (p > 0.05). Reduced proliferation was also identified in a clonogenic assay and a CFSE assay (p < 0.05) due to the MTX treatment. A reduction in the G2/M and S phases was observed accompanied by apoptosis induction with increased sub G0 phase and annexin V FITC staining. Effect of MTX was evidenced in vivo on the wound closure process after day 10 (p < 0.05) with alterations in tissue architecture and remodeling. There is a marked effect of MTX on wound healing in vivo in Skh1 mice with implications for long-term therapy and surgical interventions.
Assuntos
Proliferação de Células/efeitos dos fármacos , Queratinócitos/efeitos dos fármacos , Metotrexato/farmacologia , Cicatrização/efeitos dos fármacos , Análise de Variância , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Camundongos , Estatísticas não ParamétricasRESUMO
Several epidemiological studies have identified the cigarette smoke as a risk factor for the infection and development of tuberculosis. Nicotine is considered the main immunomodulatory molecule of the cigarette. In the present study, we evaluated the effect of nicotine in the growth of M. tuberculosis. Lung epithelial cells and macrophages were infected with M. tuberculosis and/or treated with nicotine. The results show that nicotine increased the growth of M. tuberculosis mainly in type II pneumocytes (T2P) but not in airway basal epithelial cells nor macrophages. Further, it was observed that nicotine decreased the production of ß-defensin-2, ß-defensin-3, and the cathelicidin LL-37 in all the evaluated cells at 24 and 72 h post-infection. The modulation of the expression of antimicrobial peptides appears to be partially mediated by the nicotinic acetylcholine receptor α7 since the blockade of this receptor partially reverted the production of antimicrobial peptides. In summary, it was found that nicotine decreases the production of HBD-2, HBD-3, and LL-37 in T2P during the infection with M. tuberculosis promoting its intracellular growth.
Assuntos
Células Epiteliais Alveolares/microbiologia , Mycobacterium tuberculosis/efeitos dos fármacos , Nicotina/toxicidade , Agonistas Nicotínicos/toxicidade , Tuberculose Pulmonar/microbiologia , Células A549 , Células Epiteliais Alveolares/metabolismo , Peptídeos Catiônicos Antimicrobianos/metabolismo , Carga Bacteriana , Interações Hospedeiro-Patógeno , Humanos , Macrófagos/microbiologia , Mycobacterium tuberculosis/crescimento & desenvolvimento , Tuberculose Pulmonar/metabolismo , Receptor Nicotínico de Acetilcolina alfa7/agonistas , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , beta-Defensinas/metabolismo , CatelicidinasRESUMO
The study aimed to evaluate the effect of a mango juice by-product (JBP) on upper-respiratory and gastrointestinal tract infection symptoms in children (6-8 y) in a randomized, double-blind, parallel, case-control study. For two months, children drank either flavored water (control group) or a mango JBP-based beverage (0.04 g·ml-1; treatment group); such beverage provided 1.1 g, 278.6 mg and 7.8 mg of dietary fiber, extractable polyphenols (mono-to-hepta galloyl hexosides, mangiferin), and hydrolysable polyphenols (ellagic/gallic acid) per portion, respectively. Mango JBP reduced the incidence of gastrointestinal (flatulencies and abdominal inflammation; p ≤ 0.007) and upper-tract respiratory (crystalline mucus, itchy throat, runny nose, itchy nose, and sneezing; p ≤ 0.038) and such benefits were associated to increased serum levels of PAI-I, MIP-1a, and MIP-1b (p ≤ 0.04) and decreased levels of IgG, MIF, and osteopontin (p ≤ 0.01). We concluded that JBP-based beverage has immunomodulatory properties, useful to prevent or even treat common infectious diseases in school-age children.
Assuntos
Mangifera , Infecções Respiratórias , Estudos de Casos e Controles , Criança , Trato Gastrointestinal , Humanos , Polifenóis , Infecções Respiratórias/prevenção & controleRESUMO
Diabetes has been associated with an increased risk of developing tuberculosis. The reasons related to the increased susceptibility to develop TB in type 2 diabetes mellitus (T2DM) individuals, has not been completely elucidated. However, this susceptibility has been attributed to several factors including failures and misfunctioning of the immune system. In the present study, we aimed to determine the role of anti-hyperglycemic drugs such as glyburide, insulin, and metformin to promote the killing of mycobacteria through the regulation of innate immune molecules such as host defense peptides (HDP) in lung epithelial cells and macrophages. Our results showed that metformin reduces bacillary loads in macrophages and lung epithelial cells which correlates with higher production of ß-defensin-2, -3 and -4. Since ß-defensins are crucial molecules for controlling Mycobacteriumtuberculosis growth, the present results suggest that the use of metformin would be the first choice in the treatment for T2DM2, in patients within tuberculosis-endemic areas.
Assuntos
Células Epiteliais/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Metformina/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , beta-Defensinas/genética , Contagem de Colônia Microbiana , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/microbiologia , Células Epiteliais/microbiologia , Humanos , Hipoglicemiantes/farmacologia , Pulmão/citologia , Macrófagos/imunologia , Macrófagos/microbiologia , Mycobacterium tuberculosis/imunologia , Células THP-1 , beta-Defensinas/imunologiaRESUMO
This randomized, double-blind, parallel and placebo-controlled study aimed to evaluate the effect of Bacillus coagulans GBI-30, 6086® probiotic (GanedenBC30®) against upper respiratory tract infections (URTI) and gastrointestinal tract infections (GITI) in eighty healthy school-aged children (6-8â¯years old). The participants received daily a sachet containing either GanedenBC30 (1â¯×â¯109 colony-forming units) or placebo (maltodextrin) for three months. GanedenBC30 significantly decreased the incidence of URTI symptoms including nasal congestion, bloody nasal mucus, itchy nose, and hoarseness. The duration of the URTI-associated symptoms of hoarseness, headache, red eyes, and fatigue was also decreased. GanedenBC30 supplementation also significantly reduced the incidence rate of flatulence. These beneficial effects were associated with the modulation of serum TNFα, CD163, G-CSF, ICAM-1, IL-6, IL-8, MCP-2, RAGE, uPAR, and PF4. Therefore, probiotic B. coagulans GBI-30, 6086 modulated immune-related proteins in healthy children, decreasing several URTI and GITI symptoms, thus, this functional ingredient may contribute to a healthier lifestyle.
Assuntos
Bacillus coagulans/imunologia , Gastroenteropatias/epidemiologia , Gastroenteropatias/prevenção & controle , Probióticos/farmacologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/prevenção & controle , Criança , Método Duplo-Cego , Feminino , Gastroenteropatias/imunologia , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/imunologia , Humanos , Incidência , Masculino , México/epidemiologia , Sistema Respiratório/efeitos dos fármacos , Sistema Respiratório/imunologia , Infecções Respiratórias/imunologia , Índice de Gravidade de Doença , TempoRESUMO
Type-2 Diabetes (T2D) is a predisposing cause for developing tuberculosis (TB) in low- and middle-income countries. TB-T2D comorbidity worsens clinical control and prognosis of the affected individuals. The underlying metabolic alterations for this infectious-metabolic disease are still largely unknown. Possible mediators of the increased susceptibility to TB in diabetic patients are lipids levels, which are altered in individuals with T2D. To evaluate the modulation of glycerophospholipids in patients with TB-T2D, an untargeted lipidomic approach was developed by means of ultra-performance liquid chromatography (UPLC) coupled to electrospray ionization/quadrupole time-of-flight mass spectrometry (ESI-QToF). In addition, tandem mass spectrometry was performed to determine the identity of the differentially expressed metabolites. We found that TB infected individuals with or without T2D share a common glycerophospholipid profile characterized by a decrease in phosphatidylcholines. A total of 14 glycerophospholipids were differentially deregulated in TB and TB-T2D patients and could potentially be considered biomarkers. It is necessary to further validate these identified lipids as biomarkers, focusing on the anticipate diagnosis for TB development in T2D predisposed individuals.
Assuntos
Diabetes Mellitus Tipo 2/patologia , Glicerofosfolipídeos/sangue , Tuberculose Pulmonar/patologia , Biomarcadores/sangue , Cromatografia Líquida , Comorbidade , Diabetes Mellitus Tipo 2/diagnóstico , Humanos , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Tuberculose Pulmonar/diagnósticoRESUMO
Type 2 diabetes mellitus (DM2) is strongly associated with other comorbidities such as obesity, atherosclerosis, and hypertension. Obesity is associated with sustained low-grade inflammatory response due to the production of proinflammatory cytokines. This inflammatory process promotes the differentiation of some myeloid cells, including myeloid-derived suppressor cells (MDSCs). In this study, two groups of individuals were included: DM2 patients and non-DM2 individuals with similar characteristics. Immunolabeling of CD15+ CD14- and CD33+ HLA-DR-/low was performed from whole peripheral blood, and samples were analyzed by flow cytometry, and frequencies of MDSCs and the relationship of these with clinical variables, cytokine profile (measured by cytometric bead array), and anthropometric variables were analyzed. The frequency of CD33+ HLA-DR-/low MDSCs (that produce IL-10 and TGF-ß, according to an intracellular detection) is higher in patients with DM2 (P < 0.05), and there is a positive correlation between the frequency of CD15+ CD14- and CD33+ HLA-DR-/low MDSC phenotypes. DM2 patients have an increased concentration of serum IL-5 (P < 0.05). Also, a negative correlation between the frequency of CD15+ CD14- MDSCs and LDL cholesterol was found. Our group of DM2 patients have an increased frequency of mononuclear MDSC CD33+ HLA-DR-/low that produce TGF-ß and IL-10. These cytokines have been associated with immune modulation and reduced T cell responses. DM2 and non-DM2 subjects show a similar cytokine profile, but the DM2 patients have an increased concentration of IL-5.