RESUMO
Psoriasis is a chronic inflammatory disease characterized by squamous and erythematous plaques on the skin and the involvement of the immune system. Global prevalence for psoriasis has been reported around 1-3% with a higher incidence in adults and similar proportions between men and women. The risk factors associated with psoriasis are both extrinsic and intrinsic, out of which a polygenic predisposition is a highlight out of the latter. Psoriasis etiology is not yet fully described, but several hypothesis have been proposed: 1) the autoimmunity hypothesis is based on the over-expression of antimicrobial peptides such as LL-37, the proteins ADAMTSL5, K17, and hsp27, or lipids synthesized by the PLA2G4D enzyme, all of which may serve as autoantigens to promote the differentiation of autoreactive lymphocytes T and unleash a chronic inflammatory response; 2) dysbiosis of skin microbiota hypothesis in psoriasis has gained relevance due to the observations of a loss of diversity and the participation of pathogenic bacteria such as Streptococcus spp. or Staphylococcus spp. the fungi Malassezia spp. or Candida spp. and the virus HPV, HCV, or HIV in psoriatic plaques; 3) the oxidative stress hypothesis, the most recent one, describes that the cell injury and the release of proinflammatory mediators and antimicrobial peptides that leads to activate of the Th1/Th17 axis observed in psoriasis is caused by a higher release of reactive oxygen species and the imbalance between oxidant and antioxidant mechanisms. This review aims to describe the mechanisms involved in the three hypotheses on the etiopathogeneses of psoriasis.
Assuntos
Psoríase , Masculino , Adulto , Feminino , Humanos , Pele/patologia , Autoimunidade , Autoantígenos , Peptídeos Antimicrobianos , Proteínas ADAMTSRESUMO
BACKGROUND: Psoriasis (Ps) is a chronic dermatosis characterized by erythematous-squamous plaques derived from an inflammatory response. The effect of polymorphisms in the genes that encode the members of the IL-17 family and their receptors has been studied to find an association with the susceptibility to Ps. However, the findings have not been conclusive. OBJECTIVES: To describe the association between IL-17A, IL-17F and IL-17RA gene polymorphisms and susceptibility to Ps. METHOD: A systematic review was conducted using the PubMed and Scopus databases to identify studies that evaluated the association between IL-17A, IL-17F, and IL-17RA gene polymorphisms and Ps susceptibility. This meta-analysis included reports published until June 2021. Heterogeneity was assessed using Cochran's Q-statistic test and I2 statistics. The associations between polymorphisms and Ps susceptibility were determined by pooled OR with a 95% CI. RESULTS: Fifteen studies were included. The frequency of the T allele of the IL-17F rs763780 polymorphism was significantly lower in patients with vulgar Ps (OR = 0.732, p = 0.026). The TT genotype of the IL-17F rs763780 polymorphism was significantly associated with a decreased frequency in individuals with Ps and psoriatic arthritis (PsA) (TT:TC + CC OR = 0.664, p = 0.046). Regarding IL-17RA polymorphisms, the AG genotype of the rs4819554 polymorphism showed a near-significant decrease in psoriasis risk compared to the GG genotype (AG:GG OR = 0.604, p = 0.050). Other polymorphisms in IL-17A, IL-17F and IL-17RA showed no association with Ps. CONCLUSIONS: The T allele and TT genotype of the IL-17F rs763780 polymorphism may be associated with a decreased risk of psoriasis. Therefore, the implications of this variant on psoriasis pathogenesis and treatment require further investigation.
Assuntos
Interleucina-17/genética , Psoríase/genética , Receptores de Interleucina-17/genética , Predisposição Genética para Doença , HumanosRESUMO
Background: Psoriatic Arthritis (PsA) is a seronegative spondyloarthropathy frequently associated with psoriasis. Studies have shown different members of the KIR (Killer Immunoglobulin-like Receptor) gene family may act as potential susceptibility factors; however, data have been inconsistent or with a reduced sample size. Therefore, the objective of this investigation was to determine associations between KIR genes and PsA susceptibility a meta-analysis approach. Methods: We performed a systemic search on PubMed, Scopus, and Web of Science to identify association studies linking KIR genes with PsA susceptibility. The search cut-off was May 2019. Odds Ratio (OR), 95% Confidence Intervals (95% CI), and forest plots were obtained for each KIR gene. Publication bias was evaluated by Begg and Egger linear regression tests. Results: Five articles were included in this meta-analysis. The KIR2DL2, 2DS1, 2DS2, and 2DS3 genes were positively associated with susceptibility to PsA (OR = 1.269, p = .003; OR = 1.392, p < .001; OR = 1.279, p = .002; and OR = 1.230, p = .038, respectively). In Caucasians, positive association with susceptibility to PsA were maintained by KIR2DL2, 2DS1, and 2DS2 genes (OR = 1.257, p = .005; OR = 1.535, p = .003; and OR = 1.267, p = .004, respectively). Conclusion: These associations suggest that KIR2DL2, 2DS1, 2DS2, and 2DS3 genes are susceptibility factors for PsA.
Assuntos
Artrite Psoriásica/genética , Genótipo , Receptores KIR2DL2/genética , Receptores KIR/genética , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Polimorfismo GenéticoRESUMO
Psoriasis is a chronic, autoimmune skin disease. In psoriasis, PON1 activity is diminished and peroxidation biomarkers are elevated. The most studied PON1 polymorphisms are rs662 (A > G) and rs854560 (A > T), which have been associated with the antioxidant activity of PON1, risk of cardiovascular diseases and psoriasis development. The aim of this study, was to determine the association of rs662 (A > G) and rs854560 (A > T) PON1 polymorphisms with psoriasis susceptibility in Western Mexico population. In this case-control study, we included 104 psoriasis patients and 124 control subjects. The genotyping of polymorphisms rs662 (A > G) and rs854560 (A > T) of PON1 was carried out by PCR-RFLPs. The lipid profiles were quantified by enzymatic colorimetric method, and PON1 activity was determined by spectrophotometry. The lipid profile levels, except HDL-C and atherogenic index, were higher in patients vs. controls. Patients presented lower paraoxonase and arylesterase activity. The G allele of rs662 (A > G) is associated with risk for psoriasis, while the T allele of rs854560 (A > T) is associated with low susceptibility to psoriasis. The AG haplotype was more frequent within the patient group (p < 0.05). The AA and AG genotypes of rs662 (A > G) and TT and AA genotypes of rs854560 (A > T) are associated with lower PONase and ARE activity in patients vs. controls. Patients with the G allele of rs662 (G > A) and T alleles of rs854560 (A > T) show significant differences in the lipid levels in comparison to controls. These results suggest that carriers of G allele of rs662 (A > G) present a greater susceptibility to psoriasis.
Assuntos
Arildialquilfosfatase/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Psoríase/genética , Adulto , Idoso , Alelos , Biomarcadores , Feminino , Genótipo , Haplótipos/genética , Humanos , Peroxidação de Lipídeos/genética , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Psoríase/epidemiologia , Psoríase/patologiaRESUMO
BACKGROUND: Macrophage inhibitory factor (MIF) is a pro-inflammatory cytokine secreted by several cells, including those in the immune system and the skin. The MIF gene contains the SNP -173 G> C and STR -794 CATT5-8 polymorphisms in the promoter region capable of affecting its activity. Our objective was to investigate the MIF polymorphisms as a risk factor for plaque psoriasis (PP) in the Mexican population. METHODS: We genotyped both MIF polymorphism (rs5844572 and rs755622) in 224 PP patients with a clinical and histopathological diagnosis and 232 control subjects (CS) by the PCR-RFLP method. MIF serum levels were determined by an ELISA kit. RESULTS: We found significant differences in the genotypic and allelic frequencies for the MIF -173 G>C polymorphism; carriers of the GC genotype (OR 1.51, 95% CI 1.026-2.228, p = 0.03) and the C allele (OR 1.34, 95% CI 1.005-1.807, p = 0.04) had higher odds to present with PP. Moreover, the 6C haplotype was associated with PP risk (OR 2.10, 95% CI 1.22-3.69, p < 0.01). Also, the -173 CC genotype was associated with high MIF serum levels (p < 0.05). CONCLUSIONS: The -173 GC genotype and the 6C haplotype of the MIF polymorphisms are associated with susceptibility to PP in the Mexican population.
Assuntos
Predisposição Genética para Doença/genética , Oxirredutases Intramoleculares/genética , Fatores Inibidores da Migração de Macrófagos/genética , Polimorfismo de Nucleotídeo Único/genética , Psoríase/epidemiologia , Psoríase/genética , Adulto , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCCIÓN: La hiperuricemia es común en pacientes con psoriasis. Se ha sugerido que la elevación de ácido úrico en psoriasis está fuertemente asociada con morbilidad cardiovascular. OBJETIVO: Determinar la relación entre niveles de ácido úrico, gravedad clínica medida por Psoriasis Area Severity Index (PASI), Body Surface Area (BSA) y static Physician's Global Assessment (sPGA) en pacientes con psoriasis en placas y comorbilidades ungueales y artritis psoriásica. MÉTODO: Determinación de ácido úrico sérico en 45 pacientes con psoriasis en placas y 45 controles pareados por sexo, edad e índice de masa corporal; medición de índices de gravedad clínica en pacientes y presencia de manifestaciones ungueales y articulares. RESULTADOS: Los pacientes con psoriasis presentaron niveles más elevados de ácido úrico (7.03 ± 1.47 versus 5.32 ± 1.17, p < 0.01) y mayor prevalencia de hiperuricemia asintomática (68 versus 17.8 %, p < 0.01) que los controles. Existió correlación proporcional significativa entre gravedad determinada por PASI y ácido úrico (r2 = 0.70) y entre manifestaciones articulares e hiperuricemia en pacientes con psoriasis en placas (p < 0.01; RM = 2.85, IC 95 % = 1.52-5.33). CONCLUSIONES: Los niveles séricos de ácido úrico tuvieron correlación proporcional con PASI y se asociaron con manifestaciones articulares en pacientes con psoriasis en placas. INTRODUCTION: Hyperuricemia is common in patients with psoriasis. Uric acid elevation in psoriasis has been suggested to be strongly associated with cardiovascular morbidity. OBJECTIVE: To determine the relationship between uric acid levels and clinical severity as measured by the Psoriasis Area Severity Index (PASI), body surface area (BSA) and static Physician's Global Assessment (sPGA) in patients with plaque psoriasis and nail comorbidities and psoriatic arthritis. METHOD: Determination of serum uric acid in 45 patients with plaque psoriasis and 45 controls matched by gender, age and body mass index; measurement of patient clinical severity indices and presence of nail and joint manifestations. RESULTS: Patients with psoriasis had higher levels of uric acid (7.03 ± 1.47 versus 5.32 ± 1.17, p < 0.01), and higher prevalence of asymptomatic hyperuricemia than controls (68% versus 17.8%, p < 0.01). There was significant proportional correlation between PASI-determined severity and uric acid (r2 = 0.70), and between joint manifestations and hyperuricemia in patients with plaque psoriasis (p < 0.01; OR = 2.85, 95% CI = 1.52-5.33). CONCLUSIONS: Serum uric acid levels had a proportional correlation with PASI and were associated with joint manifestations in patients with plaque psoriasis.
Assuntos
Artrite Psoriásica/fisiopatologia , Hiperuricemia/epidemiologia , Psoríase/fisiopatologia , Ácido Úrico/sangue , Adulto , Idoso , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Índice de Gravidade de DoençaRESUMO
INTRODUCTION: Studies in different populations have shown that single-nucleotide polymorphisms (SNPs) of tumor necrosis factor-alpha (TNFα) and TNF receptors 1 and 2 (TNFR1 and TNFR2) may be involved in the pathogenesis of lepromatous leprosy (LL). To further explore the results in a Mexican population, we compared the frequencies of the polymorphisms in - 308 G>A TNFA (rs1800629), - 383 A>C TNFRS1A (rs2234649), and + 196 T >G TNFSR1B (rs1061622) genes in LL patients (n = 133) and healthy subjects (n = 198). METHODOLOGY: The genotyping was performed with the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) technique. Statistical analysis was performed using the χ2 test, within the 95% confidence interval. Odds ratios (OR) were calculated and Hardy-Weinberg equilibrium was verified for all control subjects and patients. RESULTS: We found an association between the TNFSR1 -383 A>C genotype and the risk of lepromatous leprosy when leprosy patients were compared to controls (OR = 1.71, CI: 1.08-2.69, p = 0.02). Furthermore, it was also associated with the risk of LL in a dominant model (AC + CC vs AA, OR: 1.65, 95% CI: 1.05-2.057, p = 0.02). Similar genotype and allele frequencies for the SNPs TNFA - 308 G>A and TNFSR2 + 196 T>G were observed between leprosy patients and healthy subjects. CONCLUSIONS: The TNFSR1 -383 A>C could be a potential marker for the identification of high-risk populations. However, additional studies, using larger samples of different ethnic populations, are required.
Assuntos
Predisposição Genética para Doença , Hanseníase Virchowiana , Polimorfismo de Nucleotídeo Único , Receptores Tipo II do Fator de Necrose Tumoral , Receptores Tipo I de Fatores de Necrose Tumoral , Fator de Necrose Tumoral alfa , Humanos , México , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Hanseníase Virchowiana/genética , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Fator de Necrose Tumoral alfa/genética , Receptores Tipo II do Fator de Necrose Tumoral/genética , Adulto Jovem , Idoso , Frequência do Gene , Polimorfismo de Fragmento de Restrição , Estudos de Casos e Controles , Genótipo , Adolescente , Reação em Cadeia da PolimeraseRESUMO
Systemic Sclerosis (SSc) is a chronic autoimmune disease characterized by immune disorder, microvascular damage, and fibrosis. TGFB1 gene encodes for the transforming growth factor isoform 1 (TGF-ß1), one of the most important pro-fibrotic cytokines. Therefore, variants in TGFB1 and changes in its expression could be associated with the pathogenesis of SSc. We aimed to evaluate the association of TGFB1 variants (+ 869T>C [rs1982073] and + 915G > C [rs1800471]) with the TGFB1 mRNA expression and SSc risk in the Southern Mexican population. We included 56 SSc patients and 112 control subjects (CS). The genetic variants were determined by the PCR-RFLP method. The TGFB1 mRNA expression was determined by qPCR. For the + 869T>C variant, the C allele was associated with SSc risk (OR = 1.733; CI = 1.087-2.762; p = 0.020). The C allele for the + 915G>C variant was also associated with SSc risk (OR = 11.168; CI = 1.289-96.754; p = 0.023). The relative expression of TGFB1 mRNA was 1.77-fold lower in SSc patients than in CS. Carriers of polymorphic alleles (TC or CC genotypes) for the + 869T>C variant showed 3.7-fold lower mRNA expression than the TT genotype in patients and 4.81-fold lower in CS. For the + 915G>C variant, patients with GA genotype had 1.78-fold lower mRNA expression than GG genotype carriers. In conclusion, the present study showed that + 869T>C and + 915G>C variants could be SSc risk factors for patients from Southern Mexico, and these genetic variants could induce lower mRNA expression of TGFB1.
Assuntos
Escleroderma Sistêmico , Fator de Crescimento Transformador beta1 , Humanos , Fator de Crescimento Transformador beta1/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Genótipo , Escleroderma Sistêmico/genética , Frequência do GeneRESUMO
Psoriasis is a chronic inflammatory disease with a multifactorial origin that affects the skin. It is characterized by keratinocyte hyperproliferation, which results in erythemato-squamous plaques. Just as the immune system plays a fundamental role in psoriasis physiopathology, the nervous system maintains the inflammatory process through the neuropeptides and neurotransmitters synthesis, as histamine, serotonin, calcitonin gene-related peptide, nerve growth factor, vasoactive intestinal peptide, substance P, adenosine, glucagon-like peptide, somatostatin and pituitary adenylate cyclase polypeptide. In patients with psoriasis, the systemic or in situ expression of these chemical mediators and their receptors are altered, which affects the clinical activity of patients due to its link to the immune system, provoking neurogenic inflammation. It is important to establish the role of the nervous system since it could represent a therapeutic alternative for psoriasis patients. The aim of this review is to offer a detailed review of the current literature about the neuropeptides and neurotransmitters involved in the physiopathology of psoriasis.
Assuntos
Neuropeptídeos/metabolismo , Neurotransmissores/metabolismo , Pele/imunologia , Peptídeo Intestinal Vasoativo/metabolismo , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Humanos , Inflamação Neurogênica/metabolismo , Pele/metabolismoRESUMO
NK and some T cell functions are regulated by the interaction between KIR and HLA molecules. Several studies have shown an association between activating KIR genes and the development of autoimmune diseases, including psoriasis vulgaris (PsV). Our objective was to determine the association between KIR/HLA genes and genotypes with PsV in the Western mestizo Mexican population. One hundred subjects diagnosed with PsV (SP) and 108 healthy subjects (HS) were genotyped for 14 KIR genes, HLA-Bw4, HLA-C1, and HLA-C2 by PCR-single specific primer (SSP). Positive associations of the KIR3DS1 gene (odds ratio (OR) 1.959, p = 0.021), G11 genotype (OR 19.940, p = 0.008), and KIR3DS1/HLA-ABw4 (OR 2.265, p = 0.009) were found with susceptibility to PsV. In contrast, the G1 genotype (OR 0.448, p = 0.031) and KIR3DL1/HLA-Bw4Ile80 (OR 0.522, p = 0.022) were negatively associated with susceptibility to this disease. These results suggest an implication of the KIR3DS1/HLA-ABw4 genotype in PsV pathology.
Assuntos
Genótipo , Antígenos HLA-B/genética , Psoríase/genética , Receptores KIR3DS1/genética , Adolescente , Adulto , Idoso , Alelos , Feminino , Humanos , Masculino , México , Pessoa de Meia-IdadeRESUMO
Leprosy is a chronic infectious disease caused by Mycobacterium leprae. IL-12 participates in the immune response against M. leprae by regulating T cell differentiation into the Th1-type response. Several single nucleotide polymorphisms have been identified in the IL-12 gene such as 3'UTR 1188 A/C polymorphism, which is associated with different diseases. However, the relationship of this polymorphism with the immune response in leprosy has not been explored. In this case-control study, we evaluated 44 patients with lepromatous leprosy (LL) and 51 healthy subjects (HS). We aimed to determine the relationship between 3'UTR 1188 A/C polymorphism of IL-12 p40, mRNA expression, and soluble IL-12 concentration in LL patients and HS. Genotype frequencies were 41% A/A, 36% A/C, and 23% C/C in LL patients, and 47% A/A, 49% A/C, and 4% C/C in HS (p<0.05). LL patients had a lower mRNA expression of IL-12 p40 gene, whereas HS had a higher expression level. Soluble IL-12 p40 concentration was higher in LL patients than in HS (p<0.05). IL-12 p70 concentration did not differ between groups, and IL-12 p40 concentration was not significantly correlated with mRNA expression in either group. These data suggest that IL-12 p40 3'UTR 1188 A/C polymorphism is associated with greater susceptibility to lepromatous leprosy in patients from western Mexico, independently of IL-12 p40 and p70 expression levels.
Assuntos
Regiões 3' não Traduzidas/genética , Subunidade p40 da Interleucina-12/genética , Hanseníase Virchowiana/genética , Polimorfismo Genético , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Regulação da Expressão Gênica , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Interleucina-12/sangue , Subunidade p40 da Interleucina-12/sangue , Masculino , México , Pessoa de Meia-Idade , RNA Mensageiro/metabolismoRESUMO
The shift to the production of a Th1 cytokine profile during an intracellular infection has been shown to depend on antigen presenting cells-derived IL-12 and T-cell-derived IFN-gamma production. IL-18 facilitates Th1 priming in synergy with IL-12 through the stimulation of IFN-gamma production by T cells, B cells, NK cells, macrophages and DCs. A low level of IFN-gamma production in PBMC cultures from lepromatous leprosy patients (LL) has been previously reported by several groups. We evaluated the synthesis of this cytokine after exogenous addition of recombinant IL-12 and IL-18 (IL12/IL18) in order to induce recovery of the IFN-gamma levels with Mycobacterium leprae antigenic stimulation. The aim of this study was to investigate if exogenous addition of IL12/IL18 to PBMC cell cultures in the presence of M. leprae antigens could induce recovery of IFN-gamma levels. We found that IFN-gamma levels in PBMCs cultured from LL patients were reestablished after exogenous addition of exogenous IL12/IL18 and we also observed a diminished IL-18R expression. Although the molecular mechanisms of IL12/IL18 synergy have not been clearly elucidated, we assume that recombinant cytokines can activate several transcription factors that induce IFN-gamma synthesis.
Assuntos
Interferon gama/efeitos dos fármacos , Hanseníase Virchowiana/imunologia , Leucócitos Mononucleares/efeitos dos fármacos , Adjuvantes Imunológicos/farmacologia , Adulto , Idoso , Antígenos CD/efeitos dos fármacos , Antígenos CD/imunologia , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/efeitos dos fármacos , Antígenos de Diferenciação de Linfócitos T/imunologia , Antígenos de Diferenciação de Linfócitos T/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Sinergismo Farmacológico , Feminino , Humanos , Interferon gama/biossíntese , Interleucina-12/farmacologia , Interleucina-18/farmacologia , Subunidade alfa de Receptor de Interleucina-18/efeitos dos fármacos , Subunidade alfa de Receptor de Interleucina-18/imunologia , Subunidade alfa de Receptor de Interleucina-18/metabolismo , Lectinas Tipo C , Hanseníase Virchowiana/microbiologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/microbiologia , Masculino , Pessoa de Meia-Idade , Mitógenos/farmacologia , Mycobacterium leprae/imunologia , Fito-Hemaglutininas/farmacologia , Proteínas Recombinantes/farmacologiaRESUMO
Leprosy is a chronic disease caused by Mycobacterium leprae that affects the skin and peripheral nerves. It may present as one of two distinct poles: the self-limiting tuberculoid leprosy and the highly infectious lepromatous leprosy (LL) characterized by M. leprae-specific absence of cellular immune response. The pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) enhance the bactericide activities of macrophages after interaction with its receptor, CD74. Importantly, MIF also possesses chemoattractant properties, and it is a key factor in situ for the activation of macrophages and in blood to promote leukocytes migration. MIF-mediated activation of macrophages is a key process for the elimination of pathogens such as Mycobacterium tuberculosis; however, its participation for the clearance of M. leprae is unclear. The aim of this study was to evaluate the serum levels of MIF as well as MIF and CD74 expression in skin lesions of LL and compare it with healthy skin (HSk) taken from subjects attending to dermatological consult. Samples of serum and skin biopsies were taken from 39 LL patients and compared with 36 serum samples of healthy subjects (HS) and 10 biopsies of HSk. Serum samples were analyzed by ELISA and skin biopsies by immunohistochemistry (IHC). IHC smears were observed in 12 100× microscopic fields, in which percentage of stained cells and staining intensity were evaluated. Both variables were used to calculate a semi-quantitative expression score that ranged from 0 to 3+. We found no differences in MIF levels between LL patients and HS in sera. In addition, MIF was observed in over 75% of cells with high intensity in the skin of patients and HSk. Although we found no differences in MIF expression between the groups, a CD74 score statistically higher was found in LL skin than HSk (p < 0.001); this was the result of a higher percentage of cells positive for CD74 (p < 0.001). As a conclusion, we found that CD74-positive cells are intensely recruited to the skin with LL lesions. In this manner, MIF signaling may be enhanced in the skin of LL patients due to increased expression of its receptor, but further studies are required.
Assuntos
Antígenos de Diferenciação de Linfócitos B/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Interações entre Hospedeiro e Microrganismos/imunologia , Oxirredutases Intramoleculares/sangue , Hanseníase Virchowiana/imunologia , Fatores Inibidores da Migração de Macrófagos/sangue , Pele/imunologia , Adulto , Antígenos de Diferenciação de Linfócitos B/metabolismo , Biópsia , Estudos de Casos e Controles , Feminino , Voluntários Saudáveis , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Imunidade Celular , Oxirredutases Intramoleculares/imunologia , Oxirredutases Intramoleculares/metabolismo , Hanseníase Virchowiana/sangue , Hanseníase Virchowiana/patologia , Fatores Inibidores da Migração de Macrófagos/imunologia , Fatores Inibidores da Migração de Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/imunologia , Pele/citologia , Pele/patologiaRESUMO
In addition to physical barriers, neutrophils are considered a part of the first line of immune defense. They can be found in the bloodstream, with a lifespan of 6-8 h, and in tissue, where they can last up to 7 days. The mechanisms that neutrophils utilize for host defense are phagocytosis, degranulation, cytokine production, and, the most recently described, neutrophil extracellular trap (NET) production. NETs are DNA structures released due to chromatin decondensation and spreading, and they thus occupy three to five times the volume of condensed chromatin. Several proteins adhere to NETs, including histones and over 30 components of primary and secondary granules, among them components with bactericidal activity such as elastase, myeloperoxidase, cathepsin G, lactoferrin, pentraxin 3, gelatinase, proteinase 3, LL37, peptidoglycan-binding proteins, and others with bactericidal activity able to destroy virulence factors. Three models for NETosis are known to date. (a) Suicidal NETosis, with a duration of 2-4 h, is the best described model. (b) In vital NETosis with nuclear DNA release, neutrophils release NETs without exhibiting loss of nuclear or plasma membrane within 5-60 min, and it is independent of reactive oxygen species (ROS) and the Raf/MERK/ERK pathway. (c) The final type is vital NETosis with release of mitochondrial DNA that is dependent on ROS and produced after stimuli with GM-CSF and lipopolysaccharide. Recent research has revealed neutrophils as more sophisticated immune cells that are able to precisely regulate their granular enzymes release by ion fluxes and can release immunomodulatory cytokines and chemokines that interact with various components of the immune system. Therefore, they can play a key role in autoimmunity and in autoinflammatory and metabolic diseases. In this review, we intend to show the two roles played by neutrophils: as a first line of defense against microorganisms and as a contributor to the pathogenesis of various illnesses, such as autoimmune, autoinflammatory, and metabolic diseases.
RESUMO
BACKGROUND: Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae, an intracellular parasite that resides within macrophages and cannot be eliminated effectively. Solute carrier family 11a member 1 (Slc11a1) and inducible nitric oxide synthase (iNOS), both expressed in macrophages, play major roles in host defense against several intracellular pathogens. However, the roles of these molecules in natural infection with M. leprae remain unknown. OBJECTIVE: We aimed to investigate the expression of Slc11a1 and iNOS in macrophages (CD68+ cells) infiltrating skin lesions in leprosy. METHODS: Skin biopsies from 48 Mexican patients of leprosy [(33 lepromatous (LL), 15 tuberculoid (TT)] and from 10 healthy controls, were subjected to immunohistochemistry to determine expression of CD68, Slc11a1 and iNOS. RESULTS: We found a high expression of Slc11a1 and iNOS in most lepromatous leprosy samples. In tuberculoid leprosy samples, Slc11a1 expression was moderate or low, and that of iNOS was almost always low. In addition, Slc11a1 and iNOS expression levels were positively associated with bacillary loads in lepromatous leprosy lesions (P=0.05). CONCLUSIONS: These observations suggest that M. leprae infection promotes the expression of Slc11a1 and iNOS in macrophages and that lepromatous leprosy can occur despite this response.
Assuntos
Proteínas de Transporte de Cátions/análise , Hanseníase Virchowiana/metabolismo , Hanseníase Tuberculoide/metabolismo , Macrófagos/química , Óxido Nítrico Sintase Tipo II/análise , Adulto , Idoso , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Estudos de Casos e Controles , Feminino , Humanos , Hanseníase Virchowiana/patologia , Hanseníase Tuberculoide/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
Psoriasis is a chronic autoimmune inflammatory disease that affects the skin and the joints. Psoriasis is characterized by the keratinocyte proliferation, which is induced by cytokines Th1 and Th17. Patients with plaque psoriasis present a chronic inflammatory response with high levels of interleukin (IL)-12 and IL-23. Various single-nucleotide polymorphisms (SNP) have been identified in the IL12B gene, such as SNP 3' UTR 1188 A/C (SNP rs3212227), which has been associated with susceptibility to developing plaque psoriasis and with the production of IL-12 and IL-23 in individuals of different ethnic groups. In this study, we determined whether there is an association of SNP rs3212227 with the susceptibility of developing plaque psoriasis and with serum levels of IL-12 and IL-23 in Mestizo population in western Mexico. We included 112 patients with psoriasis and 112 clinical healthy individuals in the study. The frequencies of genotypes A/A, A/C, and C/C in patients with plaque psoriasis were 41, 53, and 6%, respectively, while in the control group, these were 37, 53, and 10%, respectively, without finding statistically significant differences between both groups (p>0.05). Although IL-12 and IL-23 serum levels were higher in patients than in controls, we found no significant differences. The group of patients with genotype CC presented the highest levels of IL-23 (p<0.05). These data suggest that the SNP rs3212227 phenotype is not associated with the risk of developing plaque psoriasis or with IL-12 and IL-23 levels in Mestizo population in western Mexico.
Assuntos
Regiões 3' não Traduzidas/genética , Etnicidade/genética , Predisposição Genética para Doença/genética , Subunidade p40 da Interleucina-12/genética , Polimorfismo de Nucleotídeo Único , Psoríase/genética , Adulto , Alelos , Análise de Variância , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Interleucina-12/sangue , Interleucina-23/sangue , Masculino , México , Pessoa de Meia-Idade , Razão de Chances , Psoríase/sangue , Fatores de RiscoRESUMO
INTRODUCTION: Obesity is the world's most important public health problem. Adipose tissue contributes significantly to increase pro-inflammatory mediators whose cascade begins with the union of TLR4 to its microbial ligands (TLR: Toll Like Receptors). It has been reported recently that NEFAs (Non-Esterified Fatty Acids) bind to this receptor as agonists. The purpose of our study was to determine the levels of expression of TLR4-CD14, the pro-inflammatory cytokines, the metabolic markers and the NEFAs in a group of adult, non-diabetic obese Mexicans. METHOD: A group of 210 adult middle-class Mexican non-diabetic obese patients was evaluated: 105 normal weight individuals, and 105 non-diabetic obese. On both groups, the following was tested in each patient: TLR4-CD14 receptors on monocytes in peripheral blood, inflammatory profile, HOMA-IR (Homeostasis Model Assessment-Insulin Resistance), NEFAs and each individual's anthropometric profile. RESULTS: Obesity is strongly associated with the expression of TLR4 (77%, MFI (Mean Fluorescence Index) 7.70) and CD14 (86% MFI 1.61) with 66% double positives (p = 0.000). These figures contrast with those for the normal weight individuals that constituted the control group: TLR4 (70% MFI 6.41) and CD14 (84% MFI 1.25) with 59% double positives. As for cytokine concentration, non- diabetic obese individuals vs the normal weight/thin, the numbers were: IL-1ß = 2.0 vs 2.5 pg/ml (p = NS), IL-6 = 36 vs 28 pg/ml (p = 0.030), IL-8 = 27 vs 27 pg/ml (p = NS), IL-10 = 8.4 vs 6.8 pg/ml (p = NS), TNF-α =31 vs 15 pg/ml (p = 0.000) respectively. Insulin levels were 12.1 vs 19.7 mcU/ml (p = 0.000) and the NEFAs were much higher in the obese vs normal weight/thin individuals (p = 0.000). CONCLUSION: Adipose tissue used to be thought of as mere storage of fats and energy, but it has been revealed to be an important neuro-immune-endocrine organ. Immune cells, stimulated by NEFAs, produce pro-inflammatory cytokines, which have a direct effect on oxidating radicals that directly target the release of noradrenalin. This in turn, reactivates the vicious cycle of low-grade chronic inflammation, as is now described in obesity.
RESUMO
INTRODUCTION: Patients with leprosy may be affected psychologically and socially by the negative attitude of society toward leprosy, caused by widespread ignorance and prevailing stereotypes surrounding the disease. This study aimed to determine the knowledge and attitudes toward leprosy among students at the University of Guadalajara. METHODOLOGY: This descriptive cross-sectional study included 1,300 students over 18 years of age from various Thematic University Centres in Guadalajara. Students' degree subjects included the health sciences, humanities, exact sciences (i.e., chemistry, physics), arts, biological-agricultural sciences, and administration. Students were randomly selected regardless of gender and all students were enrolled in either the first, second, or third year of their undergraduate studies. RESULTS: Overall, students showed an intermediate level of knowledge of leprosy. Results showed that 67% correctly responded that leprosy is an infectious disease, 64% knew of the presence of skin lesions, and 60% knew that a microbe causes the disease. Furthermore, 45% correctly responded that leprosy is a disease associated with poverty and 40% responded that leprosy is disabling. Only 31% stated that leprosy is curable. Negative attitudes were evident regarding the question of employing a leprosy patient (57%) and having a leprosy patient as a spouse or partner (30%). DISCUSSION: The results revealed that there is insufficient knowledge of and poor attitudes toward leprosy among students at the University of Guadalajara. It is necessary to improve current health education measures by using updated educational strategies to reduce the stigma of leprosy and the segregation of leprosy patients and their families.
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Conhecimentos, Atitudes e Prática em Saúde , Hanseníase/psicologia , Estudantes , Universidades , Adulto , Estudos Transversais , Feminino , Humanos , Hanseníase/epidemiologia , Hanseníase/prevenção & controle , Hanseníase/terapia , Masculino , México , Distribuição Aleatória , Adulto JovemRESUMO
BACKGROUND: Leprosy is a debilitating infectious disease of human skin and nerves. Genetics factors of the host play an important role in the disease susceptibility. Toll-interacting protein (TOLLIP) is an inhibitory adaptor protein within the toll-like receptor (TLR) pathway, which recognizes structurally conserved molecular patterns of microbial pathogens, initiating immune responses. The objective of this study was to investigate the association of variants in the TOLLIP gene with susceptibility to leprosy in Mexican patients. METHODS: TOLLIP polymorphisms were studied using a case-control design of Mexican patients with lepromatous leprosy (LL). The polymorphisms of TOLLIP at loci -526 C>G (rs5743854), 1309956C>T (rs3750920), 1298430C>A (rs5744015), and 1292831 G>A (rs3750919) were analyzed by PCR, with sequence-specific primers in LL patients and healthy subjects (HS) as controls. RESULTS: Genotype distributions were in Hardy Weinberg equilibrium for all sites except for rs3750920. Neither genotype nor allele frequencies were statistically different between LL patients and controls (P > 0.05). The maximum pairwise D' coefficient reached was 0.44 of linkage (P = 0.01) for all the polymorphisms except for rs5743854. The three loci haplotype comparison yielded no significant differences between groups. CONCLUSIONS: Just the individuals with genotype C/C of rs3750920 have a trend of protective effect to developing LL.
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Estudos de Associação Genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Hanseníase/genética , Adulto , Idoso , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Hanseníase/patologia , Desequilíbrio de Ligação , Masculino , México , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Receptores Toll-Like/genéticaRESUMO
La comunicación entre células inmunes e inflamatorias es mediada en gran parte por proteínas llamadas interleucinas, que promueven crecimiento, diferenciación y activación celular. Estas moléculas efectoras son producidas transitoriamente y controlan localmente la amplitud y duración de la respuesta. En ésta revisión son descritas tanto las interacciones entre citocinas y células, así como las principales características biológicas de las interleucinas involucradas en la respuesta inmune innata: IL-1, IL-6, quimiocinas, IL-10, IL-12, IL-15, IL-18, TNF-a e IFN-a, -b.