RESUMO
Helicobacter pylori (H. pylori) is a highly prevalent bacterium in our environment, directly involved in various upper digestive tract diseases, such as gastritis, peptic ulcer, and gastric cancer. Several molecules activating the immune system have been reported to be involved in containing H. pylori infection. This study is aimed at analyzing the mRNA expression of the cytokines IFN-γ, IL-17, IL-10, TGF-ß, IL-6, IL-22, IL-23, and IL-33; transcription factors T-bet, RORC, and FOXP3; enzymes ARG1, ARG2, and NOS2; and neuropeptides VIP and TAC and their respective receptors VIPR1 and TACR1 in the stomach lining of patients with severe digestive disorders. One hundred and twenty six patients have been evaluated, presenting with symptoms in the upper digestive tract, with the clinical indication for an Upper Digestive Endoscopy exam. Two fragments of the mucosa of the gastric body and antrum have been collected for anatomopathological examination and to analyze the expression of enzymes, cytokines, and transcription factors using qPCR. Expression of the ARG1 gene was seen as significantly higher in the group of patients with chronic inactive gastritis than in the control group. Expression of the TGF-ß gene and its FOXP3 transcription factor was significantly higher in the group of chronic inactive gastritis patients than in the control. Expression of IFN-γ, IL-17, IL-10, and TGF-ß and the transcription factors, T-bet and RORC, in the presence or absence of H. pylori showed no significant difference. However, the expression of FOXP3 was significantly lower in H. pylori-positive patients than that in H. pylori-negative patients. ARG1 and Treg profile appeared to be modulating the inflammatory process, protecting patients from the tissue lesions with chronic inactive gastritis. Furthermore, we suggest that IL-33 may be a crucial mediator of the immune response against an infection, after gastric mucosal damage.
Assuntos
Arginase/metabolismo , Infecções por Helicobacter/imunologia , Interleucina-33/metabolismo , Linfócitos T Reguladores/imunologia , Adulto , Biópsia , Citocinas/metabolismo , Mucosa Esofágica/imunologia , Mucosa Esofágica/microbiologia , Feminino , Mucosa Gástrica/imunologia , Mucosa Gástrica/microbiologia , Gastrite/imunologia , Gastrite/microbiologia , Perfilação da Expressão Gênica , Helicobacter pylori , Humanos , Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Antro Pilórico/imunologia , Antro Pilórico/microbiologiaRESUMO
Peri-implantitis is an infectious disease characterized by inflammation of the tissues surrounding the implant, bleeding on probing with or without suppuration, and bone loss. Peri-implant lesions contain a leukocyte infiltrate of plasma cells, lymphocytes, macrophages and neutrophils. A survey of the literature did not show any studies reporting an association between hypoxia and peri-implantitis. The aim of the present cross-sectional study was to evaluate histological changes and immunostaining for CD15, CD57 and HIF-1α in the peri-implant mucosa of patients with and without peri-implantitis. Mucosal biopsies were obtained from 18 patients with peri-implantitis and 10 control subjects without peri-implantitis at a private health care center between 2010 and 2012. The sections were fixed in 10% buffered formalin, processed and embedded in paraffin for histopathological and immunohistochemical study. Acanthosis, spongiosis and exocytosis were observed in both groups, with no significant difference between them. The peri-implantitis group showed increased immunostaining for CD15, a neutrophil marker, and HIF-1α, a tissue hypoxia marker, but no significant difference in immunostaining for CD57, a Natural Killer cell marker. The increase in neutrophil (CD15) and hypoxia (HIF-1α) markers in patients with peri-implantitis suggests an active participation of neutrophils and hypoxia in the pathogenesis of this disease. Since the present study was the first to evaluate the expression of CD15, CD57 and HIF-1α in peri-implant tissues, further studies should be performed to better understand the role of these molecules in peri-implantitis.
Assuntos
Implantes Dentários/efeitos adversos , Peri-Implantite/imunologia , Estomatite/imunologia , Idoso , Biomarcadores/análise , Biópsia , Antígenos CD57/análise , Antígenos CD57/biossíntese , Estudos Transversais , Feminino , Fucosiltransferases/análise , Fucosiltransferases/biossíntese , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/análise , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Antígenos CD15/análise , Antígenos CD15/biossíntese , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Periapical cysts and granulomas are chronic lesions caused by an inflammatory immune response against microbial challenge in the root canal. Different cell types, cytokines, and molecules have been associated with periapical lesion formation and expansion. Therefore, because of the chronic inflammatory state of these lesions, the aim of this study was to evaluate the in situ expression of matrix metalloproteinase (MMP)-14 and -19, tissue inhibitor of metalloproteinase (TIMP)-3 and -4, CD68, and inducible nitric oxide synthase (iNOS) in periapical cysts and granulomas. METHODS: Sixteen cases of periapical cysts and 15 cases of periapical granulomas were analyzed. Ten normal dental pulps were used as the negative control. Immunohistochemistry was performed with anti-MMP-19, anti-MMP-14, anti-TIMP-3, anti-TIMP-4, anti-iNOS, and anti-CD68 antibodies. RESULTS: The expression of TIMP-3, TIMP-4, iNOS, and CD68 was significantly higher in both the cyst and granuloma groups than in the control group. TIMP-4 was also significantly higher in cases of chronic apical abscess. There was also a significant difference in the expression of MMP-14 between the cyst and control groups. However, there were no differences in the expression of MMP-19 between the 3 groups. CONCLUSIONS: Our data suggest that the expression of MMP-14, TIMP-3, and TIMP-4 is associated with the development of periapical lesions.
Assuntos
Metaloproteinase 14 da Matriz/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Doenças Periapicais/metabolismo , Inibidor Tecidual de Metaloproteinase-3/metabolismo , Inibidores Teciduais de Metaloproteinases/metabolismo , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Inibidor Tecidual 4 de MetaloproteinaseRESUMO
OBJECTIVE AND DESIGN: The aim of the present study was to evaluate the immunohistochemical expression of Gal-1, Gal-3 and Gal-9 in the colon of chronic chagasic patients compared to biopsied non-chagasic patients. MATERIAL OR SUBJECTS: Thirty-two colon fragments were selected from chagasic patients with megacolon (n=25) and nonchagasic patients without megacolon (n=7). METHODS: Immunohistochemistry for Gal-1, Gal-3 and Gal-9 was performed using a common light microscope and the results were scored 0-3 according to labeling intensity. Data were analyzed statistically by the chi-square test. RESULTS: Higher Gal-1, Gal-3 and Gal-9 expression was observed in the myenteric plexus ganglia of chagasic patients compared to non-chagasic patients, p=0.0487, p=0.0019 and p=0.0325, respectively, whereas no significant differences were observed between groups regarding the expression of Gal-1, Gal-3 and Gal-9 in the muscle layer. CONCLUSION: Since Gal-1, Gal-3 and Gal-9 galectin expression was higher in the myenteric plexus ganglia of chagasic patients, we believe that these lectins may be associated with ganglionitis in the chagasic megacolon. However, since the present study was the first to report the participation of Gal-9 in Chagas disease, further investigations are needed to elucidate the role of galectin 9 in this disease.
Assuntos
Doença de Chagas/patologia , Galectina 1/biossíntese , Galectina 3/biossíntese , Galectinas/biossíntese , Idoso , Biomarcadores/análise , Proteínas Sanguíneas , Feminino , Galectina 1/análise , Galectina 3/análise , Galectinas/análise , Humanos , Imuno-Histoquímica , Masculino , Megacolo/microbiologia , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: The aim of this study was to compare the levels of IL-6, IL-10, IL-17 and IL-33 in the peri-implantar crevicular fluid (PICF) and in parotid gland saliva (PGS) of healthy patients, and peri-implantitis and peri-implant mucositis patients. MATERIALS AND METHODS: The PICF was collected from 40 implants as follows: 10 peri-implant mucositis patients, 20 peri-implantitis patients and 10 healthy patients. The PICF and PGS samples collected from each patient were quantified for IL-6, IL-10, IL-17 and IL-33 by enzymatic immunosorbent assay (ELISA). RESULTS: IL-6, IL-17 and IL-33 levels on PIFC were significantly higher in peri-implantitis group when compared to healthy group. IL-17 and IL-33 levels in PIFC were significantly higher in peri-implant mucositis group than in healthy group. There was no significant difference when comparing IL-6, IL-10, IL-17 and IL-33 levels in PGS among healthy, peri-implant mucositis and peri-implantitis groups. CONCLUSIONS: Therefore, as in patients with peri-implantitis there were significantly higher levels of IL-6, IL-17 and IL-33 in PICF, we believe that these cytokines were intensifying local inflammatory process, and contributing to clinical aspects such as increased marginal bleeding and probing depth found in patients with peri-implantitis. Furthermore, as IL-17 and IL-33 were increased in patients with peri-implant mucositis, hypothesized that these cytokines were also contributing to the inflammatory process observed in this disease.
Assuntos
Citocinas/metabolismo , Líquido do Sulco Gengival/química , Mucosite/metabolismo , Peri-Implantite/metabolismo , Adulto , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Interleucina-33/metabolismo , Interleucina-6/metabolismo , MasculinoRESUMO
BACKGROUND: Although the pathophysiology of paracoccidioidomycosis (PCM) is not completely understood, the study of immune response against fungus has provided insight into understanding the natural course of the disease and its clinical manifestations, hence contributing to the development of preventive measures and treatment proposals. The aim of this study was to evaluate the histopathological and immunological aspects involved in the role of different effector and regulatory responses, as well as the correlation between the TLRs, Galectins, Matrix Metalloproteinases and cytoplasmic proteases of mast cells in this infection. METHODS: Sixteen biopsy specimens with oral lesions of chronic PCM, as well as 13 sections of normal oral mucosa were analyzed. Histopathological and immunological aspects involved in the role of different effector and regulatory responses were evaluated. Indirect immunohistochemistry was performed for IL-17, IL-10, IL-4, TGF-ß, FoxP3, Gal-1, Gal-3, Gal-9, TLR-2, TLR-4, MMP-3 and MMP-9, as well as for chymase and tryptase for mast cells identification. Fibrosis was quantified using Picrosirius. RESULTS: There was a significant increase in the area of fibrosis and in the number of cells expressing IL-10, IL-4, IL-17, FoxP3, Gal-3, TLR-2, MMP3 and MMP9 in patients with PCM in comparison with patients in the group control. There was no difference in the expression of TGF-ß, TLR-4, Gal-1 or Gal-9. Mast cells number was found to be significantly lower in oral chronic PCM when compared to control samples after quantification of mast cells and expression of chymase and tryptase. PCM granulomas were classified to the morphological aspects in organized ou non-organized. Expression of IL-4 in non-organized granulomas was significantly higher. CONCLUSION: The proteins studied herein appear to play an important role in the development and maintenance of oral lesions of PCM, as well as in the processes of development and progression of lesions caused by the fungus and by the immune response associated with the infection.
Assuntos
Citocinas/metabolismo , Galectinas/metabolismo , Metaloproteinases da Matriz/metabolismo , Doenças da Boca , Paracoccidioidomicose/imunologia , Paracoccidioidomicose/metabolismo , Receptores Toll-Like/metabolismo , Biópsia , Contagem de Células , Humanos , Imuno-Histoquímica , Mastócitos/imunologia , Mastócitos/metabolismo , Paracoccidioidomicose/patologiaRESUMO
OBJECTIVE: The aim was to compare the inflammatory response in peri-implant mucosa between patients with peri-implantitis (PP-group) and patients with healthy peri-implant tissues (HP-group). MATERIALS AND METHODS: Two fragments of peri-implant mucosa of 18 patients were collected and serial sections were performed for histological and immunohistochemical analysis. RESULTS: When compared with HP-group, PP-group showed higher immunostained cell density for TGF-ß, IL-17 and CD31, beyond greater density of red cells, leukocytes, mast cells chymase (MCC) and mast cell tryptase (MCT). HP-group patients showed higher IL-13 expression and increased amount of collagen fibres when compared with PP-group. In PP-group there was significant positive correlation between MCT density and density of blood vessels immunostained, and between MCC density and density of blood vessels immunostained. There was significant negative correlation between the IL-17 density and collagen percentage. CONCLUSIONS: This study demonstrated that in patients with peri-implantitis there was higher of TGF-ß and IL-17, indicating that these cytokines are directly involved in the inflammatory process. Thus, understanding the influence of cytokines in the peri-implantitis installation, new therapies could be developed in order to inhibit the synthesis of IL-17 and induce synthesis of IL-13 in peri-implant tissue, contributing to increase the longevity of the implant.
Assuntos
Peri-Implantite/imunologia , Contagem de Células Sanguíneas , Quimases/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Mediadores da Inflamação/imunologia , Interleucina-17/imunologia , Masculino , Mastócitos/enzimologia , Pessoa de Meia-Idade , Peri-Implantite/patologia , Fator de Crescimento Transformador beta/imunologia , Triptases/imunologiaRESUMO
The aim of this study was to describe the role of mast cell chymase and tryptase in the progression of atherosclerosis. Forty-four sections of aortas were obtained from autopsies. We assessed the macroscopic degree of atherosclerosis, microscopic intensity of lipid deposition in the tunica intima, percentage of collagen in the tunica intima, and density of immunostained mast cells. There was no significant difference between the density of mast cell tryptase and chymase concerning ethnicity, sex, cause of death, or degree of atherosclerosis. The density of mast cell chymase was significantly higher in the nonelderly group. The percentage of collagen was significantly higher in elderly patients. There was a positive and significant correlation between the degree of macroscopic atherosclerosis and lipidosis, the density of mast cell chymase and the percentage of collagen, the density of mast cell tryptase and the percentage of collagen, and lipidosis and the density of mast cell tryptase. The degree of macroscopic lesion of atherosclerosis increased proportionally with the increase in the density of mast cell chymase and tryptase and in the intensity of lipid deposition and with the percentage of collagen in the atherosclerotic plaques. Thus, mast cells may play a crucial role in aggravating atherosclerotic lesions.
Assuntos
Aterosclerose/metabolismo , Quimases/metabolismo , Progressão da Doença , Mastócitos/enzimologia , Triptases/metabolismo , Adulto , Aorta/metabolismo , Aorta/patologia , Aterosclerose/patologia , Autopsia , Colágeno/metabolismo , Feminino , Humanos , Metabolismo dos Lipídeos , Masculino , Mastócitos/patologia , Pessoa de Meia-Idade , Túnica Íntima/metabolismo , Túnica Íntima/patologiaRESUMO
The kidney transplant is the main therapeutic alternative for end-stage kidney disease, and rejection is a major complication. The expression of proinflammatory cytokines is related to graft loss, whereas anti-inflammatory cytokines are associated with graft protection. The objective of this study is to evaluate the "in situ" expression of cytokines T helper 1 (tumor necrosis factor α [TNF-α]), T helper 17 (interleukin 17 [IL-17]), and regulatory T cell (transforming growth factor ß [TGF-ß]) and the expression of forkhead box P3 (FoxP3) in allograft kidney. We evaluated in situ expression of cytokines in allograft kidney under rejection process by indirect immunohistochemistry. Eighteen renal graft biopsies were from patients with episodes of rejection. The in situ expression of IL-17, TNF-α, and TGF-ß was significantly higher in patients with acute rejection when compared with the control group. In contrast, analysis of FoxP3 expression showed few positive cells in patients with acute rejection compared with the control group. The results suggest that the expression of proinflammatory cytokines (IL-17 and TNF-α) contributes to the mechanisms of kidney transplant rejection. The increase in TGF-ß expression might be an attempt to establish a process of immunoregulation or even to induce higher production of IL-17. The last hypothesis is supported by the observation of a reduced expression of FoxP3 and elevated levels of IL-17.
Assuntos
Fatores de Transcrição Forkhead/metabolismo , Rejeição de Enxerto/metabolismo , Rejeição de Enxerto/patologia , Interleucina-17/metabolismo , Transplante de Rim , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Idoso , Biomarcadores/metabolismo , Biópsia , Estudos de Casos e Controles , Regulação para Baixo , Feminino , Rejeição de Enxerto/diagnóstico , Humanos , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Transcriptoma , Transplante Homólogo , Regulação para CimaRESUMO
The purpose of this study was to evaluate morphologically the tongue of individuals with chronic Chagas disease (CD) in comparison to the non-chagasic ones. Twenty-four protocol cases of autopsies were selected. They were subdivided into CD patients (10 cases) and non-chagasic ones (14 cases). The morphometric analysis was accomplished for the tongue muscle and salivary glands duct lumen area. In three CD patients, perineuritis was found, and two of them showed megaesophagus and megacolon. The intensity of the inflammation in the von Ebner's glands, the tongue muscles, and the salivary glands duct lumen area was significantly higher in the CD patients. We concluded that the CD patients show salivary glands duct dilatation, which probably would have a relation with alterations in the autonomic nervous system. The inflammation found in CD patients is in accordance with that described in comparative studies on the digestive tract and heart. These morphological findings suggest that the histopathological analysis of the tongue associated with other organs, or even in an isolated manner, can add in the diagnosis and pathogenesis of the CD chronic phase.