RESUMO
The precise biological function of Interleukin-1 receptor 8 (IL-1R8) in diffuse large B-cell lymphoma (DLBCL) is still not well understood. Our goal is to decipher the profile of IL-1R8 expression status in DLBCL and to explore how IL-1R8 is involved in DLBCL progression. Utilizing a tissue microarray consisting of 70 samples of DLBCL tumors alongside 15 samples of tonsillitis, our investigation revealed a parallel expression profile of IL-1R8 between the tumor tissues and tonsillitis samples (p > 0.05). Nevertheless, an intriguing association emerged, as heightened expression of IL-1R8 correlated significantly with unfavorable survival outcomes in patients with DLBCL (p < 0.05). The status of IL-1R8 expression did not directly regulate proliferation (p > 0.05) and apoptosis (p > 0.05) in DLBCL cells via CCK8 and apoptotic assays. Subsequent chemotaxis analysis indicated that natural killer (NK) cell recruitment could be suppressed by IL-1R8 signaling in DLBCL, at least partially through CXCL1 inhibition (p < 0.05). The status of IL-1R8 expression in tumor tissues exhibited a negative correlation with the density of CD57+ NK cell infiltration (p < 0.05), while it did not demonstrate a significant association with CD3+ T cells (p > 0.05), CD68+ macrophages (p > 0.05), or S-100+ dendritic cells (p > 0.05). In line with this observation, elevated levels of NK cell infiltration demonstrated a significant positive correlation with improved overall survival (OS) among patients diagnosed with DLBCL (p < 0.05). Our data suggests the immuno-regulating potential of IL-1R8 through NK cell recruitment in DLBCL, providing novel insights into future immuno-modulating therapies.
Assuntos
Linfoma Difuso de Grandes Células B , Tonsilite , Humanos , Células Matadoras Naturais/patologia , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Macrófagos/metabolismo , Transdução de Sinais , Tonsilite/metabolismo , Tonsilite/patologiaRESUMO
The pathogenesis of recurrent tonsillitis is to be further investigated. B cell-derived interleukin (IL)-10 plays a critical role in immune regulation. Ras activation plays an important role in cancer and many immune disorders. This study aims to investigate the role of Ras activation in down regulating IL-10 expression in tonsillar B cells. Surgically removed tonsil tissues were collected from patients with recurrent acute tonsillar inflammation; B cells were isolated from the tonsillar tissues by flow cytometry sorting to be analyzed by the Ras-specific enzyme-linked immunosorbent assay and pertinent immunological approaches. We found that, compared to peripheral B cells (pBC), B cells isolated from the tonsillar tissues with recurrent inflammation (tBC) showed higher Ras activation, lower IL-10 expression and higher Bcl2L12 expression. Bcl2L12 formed a complex with GAP (GTPase activating protein) to prevent Ras from deactivating. The Ras activation triggered the MAPK/Sp1 pathway to promote the Bcl2L12 expression in B cells. Bcl2L12 prevented the IL-10 expression in tBCs, that was counteracted by inhibition of Ras or the Ras signal transduction pathway. In conclusion, Bcl2L12 interacts with Ras activation to compromise immune tolerance in the tonsils by inhibiting the IL-10 expression in tBCs. Inhibition of Bcl2L12 can restore the IL-10 expression in tBCs.
Assuntos
Linfócitos B/imunologia , Linfócitos B/metabolismo , Interleucina-10/metabolismo , Proteínas Musculares/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas ras/metabolismo , Adolescente , Adulto , Linfócitos B/patologia , Criança , Regulação para Baixo , Feminino , Proteínas Ativadoras de GTPase/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Tolerância Imunológica , Interleucina-10/genética , Masculino , Proteínas Musculares/antagonistas & inibidores , Proteínas Musculares/genética , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/genética , Recidiva , Fatores de Troca de Nucleotídeo Guanina Rho/genética , Fatores de Troca de Nucleotídeo Guanina Rho/metabolismo , Transdução de Sinais , Fator de Transcrição Sp1/antagonistas & inibidores , Fator de Transcrição Sp1/genética , Fator de Transcrição Sp1/metabolismo , Tonsilite/imunologia , Tonsilite/metabolismo , Tonsilite/patologia , Regulação para Cima , Adulto JovemRESUMO
Monocytic cells perform crucial homeostatic and defensive functions. However, their fate and characterization at the transcriptomic level in human tissues are partially understood, often as a consequence of the lack of specific markers allowing their unequivocal identification. The 6-sulfo LacNAc (slan) antigen identifies a subset of non-classical (NC) monocytes in the bloodstream, namely the slan+ -monocytes. In recent studies, we and other groups have reported that, in tonsils, slan marks dendritic cell (DC)-like cells, as defined by morphological, phenotypical, and functional criteria. However, subsequent investigations in lymphomas have uncovered a significant heterogeneity of tumor-infiltrating slan+ -cells, including a macrophage-like state. Based on their emerging role in tissue inflammation and cancer, herein we investigated slan+ -cell fate in tonsils by using a molecular-based approach. Hence, RNA from tonsil slan+ -cells, conventional CD1c+ DCs (cDC2) and CD11b+ CD14+ -macrophages was subjected to gene expression analysis. For comparison, transcriptomes were also obtained from blood cDC2, classical (CL), intermediate (INT), NC, and slan+ -monocytes. Data demonstrate that the main trajectory of human slan+ -monocytes infiltrating the tonsil tissue is toward a macrophage-like population, displaying molecular features distinct from those of tonsil CD11b+ CD14+ -macrophages and cDC2. These findings provide a novel view on the terminal differentiation path of slan+ -monocytes, which is relevant for inflammatory diseases and lymphomas.
Assuntos
Amino Açúcares/metabolismo , Células Dendríticas/metabolismo , Macrófagos/metabolismo , Monócitos/metabolismo , Tonsila Palatina/metabolismo , Tonsilite/genética , Estudos de Casos e Controles , Células Cultivadas , Células Dendríticas/citologia , Perfilação da Expressão Gênica , Humanos , Macrófagos/citologia , Monócitos/citologia , Tonsila Palatina/citologia , Tonsilite/metabolismo , Tonsilite/patologiaRESUMO
INTRODUCTION: We have examined 92 children aged between 6 and 15, suffering from chronic tonsillitis (CT). Tumor necrosis factor (TNF-α) and interleukin 1ß and 6 (IL-1ß and IL-6) contents have been defined in saliva. The control set comprised 17 healthy children. Cytokine content was defined with the enzyme multiplied immunoassay sets (Vektor Best Ltd., Russia) by enzyme-linked immunosorbent assay. The statistic analysis and data processing were carried out with statistic analysis programs (version 3.2, R Foundation for Statistical Computing, Vienna, Austria). RESULTS: The content of cytokines TNF-α, IL-1, IL-6 in CT children's saliva was high against the healthy children, yet the statistically significant differences were only noted for IL-6. In the CT group the median value of this factor (12.5) was significantly higher than in the control set (6.72) (p=0.01 in Mann-Whitney assessment). IL-6 was chosen as the basic factor for the mathematic model; its combinations in the form of a multi-factor logistic regression were given consideration. From out of the three possible models there was just one that had all the coefficients statistically significantly different from zero (TNF-α - IL-6). It was chosen as the basic diagnostic model for chronic tonsillitis. The created model's sensitivity is 80.4%, while its specificity is 82.4%. DISCUSSION: The revealed IL-6 dominance in saliva at CT can be is attributable to permanent antigenic challenge characteristic of the toxic allergic CT since, as previously shown, there are living proliferating microorganisms in the palatal tonsil tissues and their blood- and lymph vessels at CT. CONCLUSION: The conducted ROC-analysis has demonstrated high sensitivity and specificity of the mathematical model, which enabled us to recommend determination of IL-6 in the saliva of the children suffering from CT as an additional diagnostic criterion.
Assuntos
Citocinas/metabolismo , Saliva , Tonsilite/metabolismo , Adolescente , Criança , Humanos , Interleucina-6 , Federação Russa , Fator de Necrose Tumoral alfaRESUMO
OBJECTIVE: Fractalkine, member of chemokine family, is involved in many inflammatory processes in the human body. The aim of this study is to compare expression levels of fractalkine ligand and its receptor in chronic tonsillitis and hypertrophic tonsil samples. METHODS: The study was conducted at Baskent University Departments of Otorhinolaryngology and Medical Genetics. It is designed as a prospective, non-randomized, controlled clinical study. Total 97 samples, obtained from adenotonsillectomy due to chronic tonsillitis or tonsillar hypertrophy, were participated in the study. Fractalkine and its receptor expression levels were determined and comparison was made between the tissue groups. c.839C>T (T280M) polymorphism of fractalkine receptor was analyzed, then relationship between polymorphism and the expression level of fractalkine receptor was investigated. RESULTS: Fractalkine receptor expression was significantly higher in the hypertrophic tonsil group than chronic tonsillitis group (p<0.05). CONCLUSION: Fractalkine, member of chemokine family, and its receptor may play role in preventing chronic-recurrent tonsillitis.
Assuntos
Receptor 1 de Quimiocina CX3C/metabolismo , Quimiocina CX3CL1/metabolismo , Tonsila Palatina/metabolismo , Tonsilite/metabolismo , Adenoidectomia , Tonsila Faríngea/metabolismo , Tonsila Faríngea/patologia , Tonsila Faríngea/cirurgia , Receptor 1 de Quimiocina CX3C/genética , Criança , Pré-Escolar , Doença Crônica , Feminino , Humanos , Hipertrofia , Masculino , Tonsila Palatina/patologia , Tonsila Palatina/cirurgia , Polimorfismo de Nucleotídeo Único , Tonsilectomia , Tonsilite/cirurgiaRESUMO
Expression profiles of CXC- and CC-chemokines in various forms of tonsillar disease were studied to evaluate whether certain chemokines play a predominant role in a specific subset of tonsillar disease. Total RNA was isolated from 89 biopsies (21 hyperplastic palatine tonsils, 25 adenoids, 16 chronic inflammatory palatine tonsils and 27 chronic inflammatory palatine tonsils with histological prove of acute inflammation), reverse transcribed and subjected to PCR amplifying IL-8, Gro-alpha, eotaxin-1, eotaxin-2, MCP-3, MCP-4 and RANTES. 2% agarose gel electrophoresis revealed a predominance of IL-8 in the chronic inflammatory palatine tonsil group compared to tonsillar hyperplasia. Furthermore, eotaxin-2 was strongly overexpressed in adenoid samples compared to chronic inflammatory specimens. Our data suggest that the majority of diseases related to adenoid formation are mediated via an eotaxin-2 expression, whereas chronic inflammatory tonsillitis is associated with IL-8 upregulation. These data imply that adenoids are related to a Th-2, and chronic inflammatory tonsillitis to a Th-1 based immune response.
Assuntos
Tonsila Faríngea/metabolismo , Tonsila Faríngea/patologia , Quimiocinas/biossíntese , Tonsila Palatina/metabolismo , Tonsila Palatina/patologia , Tonsilite/metabolismo , Adulto , Quimiocinas/genética , Criança , Pré-Escolar , Expressão Gênica , Humanos , Hiperplasia/genética , Hiperplasia/metabolismo , Tonsilite/genéticaRESUMO
We aimed to determine whether advanced oxidation protein product (AOPP) levels can serve as a marker of oxidative stress in paediatric patients with chronic tonsillitis. Thirty children with chronic tonsillitis and 30 healthy children (control group) were recruited from the Otorhinolaryngology (ORL) and Paediatric Surgery departments, respectively, of Dumlupinar University Hospital. In the patient group, blood samples were collected before tonsillectomy, and tonsil tissue was sampled during the operation. Blood samples were also obtained from the control subjects. AOPP levels in the serum and tonsil tissue were measured by the spectrophotometric method. Serum AOPP levels were significantly higher in the patient group (13.1 ± 3.3 ng/ml) than in the control group (11.6 ± 2.3 ng/ml; P < 0.05). In addition, the mean AOPP level (41.9 ± 13.5 ng/mg protein) in the tonsil tissue in the patient group was significantly higher than the mean serum AOPP levels in the control and patient groups (P < 0.05). AOPP levels are elevated in the tonsil tissue and serum of patients with chronic tonsillitis compared to the serum AOPP levels in healthy controls. AOPPs may represent a novel class of pro-inflammatory molecules that are involved in oxidative stress in chronic tonsillitis. AOPPs may be used as a marker of oxidative stress in paediatric patients with chronic tonsillitis.
Assuntos
Produtos da Oxidação Avançada de Proteínas/análise , Estresse Oxidativo , Tonsila Palatina/química , Tonsila Palatina/metabolismo , Tonsilite/sangue , Tonsilite/metabolismo , Produtos da Oxidação Avançada de Proteínas/sangue , Biomarcadores/sangue , Criança , Doença Crônica , Feminino , Humanos , MasculinoRESUMO
OBJECTIVES: A number of otolaryngic conditions such as chronic tonsillitis, adenoid hypertrophy, and obstructive sleep apnea are associated with oxidative stress and elevated levels of serum oxidants. The objective of this study is to measure changes in urine biomarkers of oxidative stress in children after adenotonsillectomy. METHODS: Twenty-two children with sleep disordered breathing (SDB) with tonsil and adenoid hypertrophy were enrolled prior to adenotonsillectomy. Controls consisted of 20 healthy children. Urine samples were collected from all patients. Levels of three urinary biomarkers for oxidative status, 8-hydroxy-2-deoxyguanosine (8-OxodG), F(2)-isoprostane, and malondialdehyde (MDA) were measured using high performance liquid chromatography. For the study group, urine samples were repeated 3 weeks after surgery. RESULTS: In the study group, preoperative urinary levels of 8-OxodG were higher than in controls (p=0.015). Levels decreased after surgery compared to preoperative levels (p=0.002), and reached control levels (p=0.167) at 3 weeks. Levels of urinary F(2)-isoprostane were similar in both groups (p=0.252), but decreased significantly after surgery (p=0.020). CONCLUSIONS: Children with SDB have elevated levels of urinary 8-OxodG, a marker of oxidative stress. Adenotonsillectomy results in decreased 8-OxodG and F(2)-isoprostane. These findings suggest that urine analysis may represent a valuable tool for the measurement of oxidative stress.
Assuntos
Biomarcadores/urina , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/urina , Síndromes da Apneia do Sono/cirurgia , Tonsilite/cirurgia , Adenoidectomia , Criança , Pré-Escolar , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Hipertrofia/cirurgia , Masculino , Síndromes da Apneia do Sono/metabolismo , Tonsilectomia , Tonsilite/metabolismoRESUMO
Squamous cell tonsil carcinoma is the most frequent form of oropharyngeal cancer, representing 70-80% of the total of head and neck malignant tumors. Poor clinical symptoms make that 60-80% of patients with squamous cell tonsil carcinoma have a late diagnosis, in the third and fourth stages, when the tumor exceeds the organ limits, invading the pharyngeal wall or the tongue base, being associated with metastases in the laterocervical lymphatic ganglions. The tumor necrosis factor alpha (TNF-α) represents an important inflammation mediator associated to carcinogenesis and even to tumor progression. We evaluated the seric values of TNF-α in a group of patients with tonsil cancer in comparison to a group of patients with chronic tonsillitis, as well as the reaction of mastocytes and macrophages in the two types of tonsil lesions. Seric levels of TNF-α in squamous cell tonsil carcinoma were quite high, varying from 1000 to 2000 pg÷mL, and in four patients, with poorly differentiated tonsil carcinoma in the fourth stage, the TNF-α values varied from 2000 to 4000 pg÷mL. In the patients undergoing radiotherapy, the TNF-α seric levels were within normal limits. In chronic tonsillitis, the TNF-α seric level varied from 10 to 200 pg÷mL. There were not observed any significant differences between the two types of tonsil lesions, regarding the macrophages and mast cells density on the surface unit.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Tonsilares/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Idoso , Feminino , Humanos , Inflamação , Macrófagos/metabolismo , Masculino , Mastócitos/metabolismo , Pessoa de Meia-Idade , Faringe/patologia , Tonsilite/metabolismoRESUMO
OBJECTIVE: To elucidate specific cytokine and chemokine markers in patients diagnosed with pediatric autoimmune neuropsychiatric disorder associated with streptococcus (PANDAS). STUDY DESIGN: Prospective cohort study. STUDY SETTING: Academic university hospital. METHODS: Tonsil tissue was collected from 24 patients and organized into 3 groups: experimental PANDAS cohort (12 patients), group A beta hemolytic streptococcus control cohort (6 patients), and obstructive sleep apnea control cohort (6 patients). Each tissue sample was extracted with MSD Tris lysis buffer, and protein lysates were analyzed for human chemokines and cytokines by the Human Cytokine 30-Plex Assay on the Mesoscale System. RESULTS: We identified a significant difference in expression regarding the 8 following cytokines when comparing the experimental PANDAS, group A beta hemolytic streptococcus, and obstructive sleep apnea control cohorts: tumor necrosis factor-α and eotaxin-3. In addition, our group also identified a significant reduction in the expression of interleukin (IL)-8, interferon inducible protein-10, IL-17a, interferon-γ, IL-10, and IL-12 across the aforementioned groups. CONCLUSIONS: Patients diagnosed with PANDAS appear to maintain significantly different concentrations of cytokines when compared with patients afflicted by chronic group A beta hemolytic streptococcus infections and obstructive sleep apnea. As a result, one could potentially use the described characterization of immunologic markers as a basis for future mechanistic and epidemiological studies.
Assuntos
Doenças Autoimunes/metabolismo , Citocinas/metabolismo , Infecções Estreptocócicas/metabolismo , Streptococcus pyogenes , Tonsilite/metabolismo , Adolescente , Doenças Autoimunes/complicações , Doenças Autoimunes/cirurgia , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino , Transtorno Obsessivo-Compulsivo , Projetos Piloto , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/cirurgia , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/cirurgia , Tonsilectomia , Tonsilite/etiologia , Tonsilite/cirurgiaRESUMO
CONCLUSION: This study demonstrated that the common immunological mechanism, which involves aberration of immunoglobulin and T-cell distribution in histologically distinctive tonsils, may be associated with the pathogenesis of tonsillar focal infection. OBJECTIVES: Tonsillar focal infection comprises a group of relatively common diseases combined with chronic tonsillar infection, is associated with unusual immune responses in tonsils, and may cause lesions in another distant target organ. This study aimed to investigate the distribution of inflammatory T cells and T-cell regulatory elements, such as programmed cell death-1 (PD-1) and Fork head box protein 3 (Foxp3), immunoglobulin production, and histological characteristics in tonsils from patients with tonsillar focal infection. METHODS: Immunohistochemistry and reverse transcription-polymerase chain reaction (PCR) were used to compare the expression of CD8(+) T cells, immunoglobulins, and cytokines associated with immunoglobulin production in the tonsils of patients with IgA nephropathy (IgAN), palmoplantar pustulosis (PPP), rheumatoid arthritis (RA), and chronic tonsillitis. RESULTS: The overexpression of CD8(+) T cells combined with decreased expression of Foxp3 and PD-1 and the aberration of immunoglobulin production, which may be due to the elevated expression of activation-induced deaminase (AID), B-cell-activating factor of the TNF family (BAFF), supporting isotype switching, and B-cell survival in the histologically distinctive tonsils.
Assuntos
Artrite Reumatoide/imunologia , Linfócitos T CD8-Positivos/fisiologia , Infecção Focal/imunologia , Glomerulonefrite por IGA/imunologia , Imunoglobulinas/metabolismo , Tonsilite/imunologia , Adulto , Artrite Reumatoide/metabolismo , Fator Ativador de Células B/metabolismo , Antígenos CD8/metabolismo , Microambiente Celular , Citidina Desaminase/metabolismo , Feminino , Infecção Focal/metabolismo , Infecção Focal/patologia , Fatores de Transcrição Forkhead/metabolismo , Glomerulonefrite por IGA/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Tonsila Palatina/patologia , Receptor de Morte Celular Programada 1/metabolismo , Proteínas/metabolismo , Sindecana-1/metabolismo , Tonsilite/metabolismo , Tonsilite/patologiaRESUMO
To emphasize the effectiveness of adenosine deaminase (ADA) enzyme, which has important roles in the differentiation of lymphoid cells, and oxidative stress in patients with chronic tonsillitis. Serum and tissue samples were obtained from 25 patients who underwent tonsillectomy due to recurrent episodes of acute tonsillitis. In the control group, which also had 25 subjects, only serum samples were taken as obtaining tissue samples would not have been ethically appropriate. ADA enzyme activity, catalase (CAT), carbonic anhydrase (CA), nitric oxide (NO) and malondialdehyde (MDA) were measured in the serum and tissue samples of patients and control group subjects. The serum values of both groups were compared. In addition, the tissue and serum values of patients were compared. Serum ADA activity and the oxidant enzymes MDA and NO values of the patient group were significantly higher than those of the control group (p < 0.001), the antioxidant enzymes CA and CAT values of the patient group were significantly lower than those of the control group (p < 0.001). In addition, while CA, CAT and NO enzyme levels were found to be significantly higher in the tonsil tissue of the patient group when compared to serum levels (p < 0.05), there was no difference between tissue and serum MDA and ADA activity (p > 0.05). Elevated ADA activity may be effective in the pathogenesis of chronic tonsillitis both by impairing tissue structure and contributing to SOR formation.
Assuntos
Adenosina Desaminase/metabolismo , Anidrases Carbônicas/metabolismo , Catalase/metabolismo , Malondialdeído/metabolismo , Óxido Nítrico/metabolismo , Estresse Oxidativo , Tonsilite/enzimologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Doença Crônica , Feminino , Humanos , Masculino , Tonsilectomia , Tonsilite/metabolismo , Tonsilite/cirurgia , Adulto JovemRESUMO
OBJECTIVE: To investigate the mode of presentation, cytologic features of the plasmacytoid dendritic cells (pDC), and the expression of CD123 and its significance in Kikuchi's disease. METHODS: CD123 expression was evaluated by EliVision immunohistochemical staining in formalin-fixed and paraffin-embedded tissues from 30 cases of Kikuchi's disease, 5 cases of T cell lymphoma, 10 cases of reactive lymphoid hyperplasia and 10 cases of chronic tonsillitis. RESULTS: Clusters of CD123 positive PDC were observed in Kikuchi's disease (28 of 30 cases, 93.3%) and the staining intensity was more prominent in the PDC at the periphery of the lesion and around the high endothelial venule-like vessels. CD123 showed three staining patterns: membranous (10 cases, 33.3%), cytoplasmic (10 cases, 33.3%), and membranous and cytoplasmic (8 cases, 26.7%). In the control group, CD123 showed cytoplasmic staining in reactive hyperplasia and chronic tonsillitis. Regarding the staining intensity, 12 of 28 cases (42.9%) were 3+ for CD123, 8 of 28 cases (28.6%) were 2+, and 8 of 28 cases (28.6%) were 1+. In contrast, PDC clusters with 1+ staining intensity were observed in 1 of 10 cases of reactive lymphoid hyperplasia; 2 of 10 chronic tonsillitis diseases; and much less in T cell lymphoma. CONCLUSIONS: Large cluster of PDC is detected in both proliferative and necrotizing types of Kikuchi's disease, making this a useful adjunctive diagnostic marker.
Assuntos
Células Dendríticas/metabolismo , Células Dendríticas/patologia , Linfadenite Histiocítica Necrosante/metabolismo , Linfadenite Histiocítica Necrosante/patologia , Adulto , Idoso , Doença Crônica , Feminino , Humanos , Linfoma de Células T/metabolismo , Linfoma de Células T/patologia , Masculino , Pessoa de Meia-Idade , Pseudolinfoma/metabolismo , Pseudolinfoma/patologia , Coloração e Rotulagem , Tonsilite/metabolismo , Tonsilite/patologiaRESUMO
OBJECTIVE: Tonsillar hypertrophy cells appear to have an altered lipid metabolism as evidenced by modulated inflammatory cytokines that affect tissue lipid metabolism. The aim of this study was to investigate differences in tissue fat composition between obstructive sleep apnea (OSA) and recurrent infective tonsillitis (RT) in children. METHODS: Tonsillar tissues were collected from 114 patients with OSA and 92 patients with RT, aged 4-10 years, during tonsillectomy. The tissue lipid extracts were analyzed by gas liquid chromatography for a comprehensive fatty acid profile. RESULTS: In the tonsillitis tissue, the levels of palmitoleic acid (16:1n-7; P=0.002) and oleic acid (18:1n-9; P=0.003) were higher, and the level of stearic acid (18:0; P=0.004) was lower than that in the hyperplastic tonsillar tissue. Overall, tonsillar tissue of patients with RT had a significant increase in the total monounsaturated fatty acids (+9.9%; P<0.001) and the fatty acid desaturation index (+20.5%; P<0.001). Furthermore, oleic acid content of tonsillar tissue was positively correlated with BMI (r=0.20, P=0.004), snoring (r=0.16, P=0.022) and hypertrophy grade (r=0.18, P=0.023), which remain significant in the subgroup analysis by hypertrophy type. CONCLUSIONS: The change in the fatty acid composition may be regarded as an indicator of altered lipid metabolism occurring in vivo during human tonsillar hypertrophy, which might be linked to the severity or type of the tissue damage.
Assuntos
Ácidos Graxos/metabolismo , Apneia Obstrutiva do Sono/metabolismo , Tonsilite/metabolismo , Biomarcadores/metabolismo , Biópsia por Agulha , Estudos de Casos e Controles , Criança , Pré-Escolar , Cromatografia Líquida/métodos , Ácidos Graxos/análise , Ácidos Graxos Monoinsaturados/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Ácido Oleico/metabolismo , Prognóstico , Estudos Prospectivos , Recidiva , Valores de Referência , Medição de Risco , Apneia Obstrutiva do Sono/patologia , Apneia Obstrutiva do Sono/cirurgia , Tonsilectomia/métodos , Tonsilite/patologia , Tonsilite/cirurgia , Resultado do TratamentoRESUMO
This study aimed to evaluate the palatine tonsils of patients with chronic tonsillitis and spinocellular carcinoma to determine the presence of nano-sized particles. Tonsil samples from adult patients with chronic tonsillitis and spinocellular carcinoma of the palatine tonsil were dried and analyzed using a scanning electron microscope with the X-ray microprobe of an energy-dispersive spectroscope. Demographic data and smoking histories were obtained. The principal metals found in almost all tissues analyzed were iron, chromium, nickel, aluminum, zinc, and copper. No significant difference in elemental composition was found between the group of patients with chronic tonsillitis and the group with spinocellular carcinoma of the palatine tonsil. Likewise, no significant difference was found between the group of smokers and the group of nonsmokers. The presence of various micro- and nano-sized metallic particles in human tonsils was confirmed. These particles may potentially cause an inflammatory response as well as neoplastic changes in human palatine tonsils similar to those occurring in the lungs. Further and more detailed studies addressing this issue, including studies designed to determine the chemical form of the metals detected, studies devoted to quantitative analysis, biokinetics, and to the degradation and elimination of nanoparticles are needed for a more detailed prediction of the relation between the diagnosis and the presence of specific metal nanoparticles in tonsillar tissue.
Assuntos
Carcinoma de Células Escamosas/química , Nanopartículas Metálicas/análise , Neoplasias Tonsilares/química , Tonsilite/metabolismo , Adulto , Idoso , Doença Crônica , Exposição Ambiental , Humanos , Microscopia Eletrônica de Varredura , Pessoa de Meia-Idade , Tonsila Palatina/química , Adulto JovemRESUMO
In the issue we demonstrate results of Epstein-Barr virus (EBV) detection by chromogenic in situ hybridization (CISH) in epithelial and lymphoid cells of the palatine tonsil in patients with chronic tonsillitis. Virus genome detections were performed using RNA-probes with digoxigenin-labeled oligonucleotides which target EBV RNA, notably RNA-transcripts of virus genomic DNA. The obtained data confirm the virus lymphotropism and also tropism to epithelial cells of both surface and cryptal epithelium of the palatine tonsil. CISH method in combination with immunohistochemical identification of virus protein products opens new possibilities for clinicopathological monitoring of the different clinical forms of the chronic tonsillitis, as well as new horizon for understanding intrinsic role of EBV in tonsillar pathology.
Assuntos
Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/metabolismo , Herpesvirus Humano 4/metabolismo , Hibridização In Situ/métodos , Tonsilite/diagnóstico , Tonsilite/metabolismo , Doença Crônica , DNA Viral/genética , DNA Viral/metabolismo , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/patologia , Feminino , Herpesvirus Humano 4/genética , Humanos , Masculino , RNA Viral/genética , RNA Viral/metabolismo , Tonsilite/genética , Tonsilite/patologia , Tonsilite/virologiaRESUMO
OBJECTIVE: To analyze soluble and membrane-bound peptidase activities in the tonsils and adenoids removed from patients with adenoid hyperplasia, tonsillar hyperplasia and chronic tonsillitis. METHODS: A total of 48 tissue samples from patients undergoing adenoidectomy and tonsillectomy for adenoid hyperplasia, tonsillar hyperplasia or chronic tonsillitis were analyzed. The catalytic activity of a pool of peptidases in the soluble (dipeptidyl peptidase IV, aminopeptidase A, aminopeptidase N and cystinyl aminopeptidase) and membrane-bound (prolyl endopeptidase, aspartyl aminopeptidase, aminopeptidase B and pyroglutamyl peptidase I) fractions was measured fluorometrically. RESULTS: The activity of membrane-bound aminopeptidase B was higher in cases of chronic tonsillitis and adenoid hyperplasia than in tonsillar hyperplasia, p=0.004. Soluble dipeptidyl peptidase IV and membrane-bound pyroglutamyl peptidase I were found to be more active in tissues from male chronic tonsillitis tissues, p<0.05, while membrane-bound aminopeptidase B activity was higher in tissues of females with tonsillar hyperplasia, p<0.001. In the case of chronic tonsillitis, soluble aminopeptidase A was found to have a higher level of activity in tissues from children than those from adults, p=0.005. CONCLUSIONS: Our results suggest a potential role of soluble aminopeptidase A, soluble dipeptidyl peptidase IV, membrane-bound aminopeptidase B and membrane-bound pyroglutamyl peptidase I in the pathobiology of adenoid hyperplasia, tonsillar hyperplasia and chronic tonsillitis that is differently regulated as a function of gender. These finfings may modify in the future the clinical approach to these diseases.
Assuntos
Tonsila Faríngea/metabolismo , Aminopeptidases/metabolismo , Tonsila Palatina/metabolismo , Tonsila Faríngea/patologia , Aminopeptidases/análise , Análise de Variância , Biomarcadores/análise , Criança , Pré-Escolar , Doença Crônica , Estudos de Coortes , Dipeptidil Peptidase 4/análise , Dipeptidil Peptidase 4/metabolismo , Feminino , Glutamil Aminopeptidase/análise , Glutamil Aminopeptidase/metabolismo , Humanos , Hiperplasia/metabolismo , Hiperplasia/patologia , Masculino , Tonsila Palatina/patologia , Piroglutamil-Peptidase I/análise , Piroglutamil-Peptidase I/metabolismo , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Tonsilectomia/métodos , Tonsilite/metabolismo , Tonsilite/patologia , Tonsilite/cirurgiaRESUMO
Exhaled nitric oxide (eNO) is a highly reactive biological mediator that has recently been associated with chronic tonsillar disease in adults, but there are no published data concerning eNO levels in their pediatric counterparts. The aim of this study is to measure mean eNO levels in children with chronic adenotonsillitis or adenotonsillar hypertrophy, and assess the effects of potential confounding factors. Children aged 3-17 years were divided into three groups (chronic adenotonsillitis, adenotonsillar hypertrophy and controls). Their eNO levels were measured in accordance with the international guidelines, and their other clinical and anamnestic characteristics were recorded. The mean eNO level in the children with chronic adenotonsillitis was slightly higher than that in the other groups, but there was no statistically significant between-group difference. Age (p=0.009), allergy (p=0.05) and body mass index (p=0.03), but not the mean grade of adenoidal or tonsil hypertrophy, were all statistically related to mean eNO levels. These preliminary results indicate the lack of an increase in mean eNO levels in children with chronic adenotonsillar disease, with no substantial difference between children with chronic adenotonsillitis and those with adenotonsillar hypertrophy.
Assuntos
Tonsila Faríngea/patologia , Testes Respiratórios , Expiração , Óxido Nítrico/análise , Tonsila Palatina/patologia , Doenças Faríngeas/diagnóstico , Tonsilite/diagnóstico , Adolescente , Análise de Variância , Biomarcadores/análise , Criança , Pré-Escolar , Doença Crônica , Estudos Transversais , Feminino , Humanos , Hipertrofia , Itália , Masculino , Doenças Faríngeas/metabolismo , Doenças Faríngeas/fisiopatologia , Valor Preditivo dos Testes , Tonsilite/metabolismo , Tonsilite/fisiopatologiaRESUMO
Fas-associated death domain protein is a key component of the extrinsic apoptotic pathway. In addition, in animal models, Fas-associated death domain protein phosphorylation at serine 194 has been shown to affect cell proliferation, especially in T lymphocytes. The importance of Fas-associated death domain protein phosphorylation at serine 194 for the proliferation of B lymphocytes, however, is uncertain. Here we show in reactive lymph nodes that serine 194 phosphorylated Fas-associated death domain protein is expressed predominantly in the dark (proliferative) zone of germinal centers. In B-cell non-Hodgkin lymphoma cell lines, serine 194 phosphorylated Fas-associated death domain protein levels are substantially higher in highly proliferating cells and lower in serum-starved cells. We also used immunohistochemical analysis to assess Fas-associated death domain protein phosphorylation at serine 194 expression in 122 B-cell non-Hodgkin-type lymphomas. The mean percentage of serine 194 phosphorylated Fas-associated death domain protein positive tumor cells was 81% in Burkitt lymphoma, 41% in diffuse large B-cell lymphoma, 18% in follicular lymphoma, 18% in plasma cell myeloma, 12% in extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, 11% in mantle cell lymphoma, and 2% in chronic lymphocytic leukemia/small lymphocytic lymphoma (P < .0001, Kruskal-Wallis test). Furthermore, in chronic lymphocytic leukemia/small lymphocytic lymphoma, serine 194 phosphorylated Fas-associated death domain protein was detected predominantly in proliferation centers. In the entire study group, the percentage of cells positive for serine 194 phosphorylated Fas-associated death domain protein correlated significantly with the proliferation index Ki-67 (Spearman R = 0.9, P < .0001). These data provide evidence that serine 194 phosphorylated Fas-associated death domain protein is involved in the proliferation of normal and neoplastic B cells and has features of a novel proliferation marker.
Assuntos
Ciclo Celular/fisiologia , Proteína de Domínio de Morte Associada a Fas/metabolismo , Linfoma de Células B/patologia , Serina/metabolismo , Biomarcadores Tumorais/metabolismo , Contagem de Células , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Núcleo Celular/patologia , Proliferação de Células , Centro Germinativo/metabolismo , Centro Germinativo/patologia , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Linfonodos/metabolismo , Linfonodos/patologia , Linfadenite/metabolismo , Linfadenite/patologia , Linfoma de Células B/metabolismo , Fosforilação , Tonsilite/metabolismo , Tonsilite/patologiaRESUMO
OBJECTIVE: To analyse peptidase activities in the removed tonsils and adenoids from patients with chronic tonsillitis, tonsillar hyperplasia and adenoid hyperplasia. METHODS: We have analyzed 48 tissue samples from patients undergoing tonsillectomy and adenoidectomy for chronic tonsillitis, tonsillar hyperplasia or adenoid hyperplasia. Tonsillectomy and adenoidectomy samples were collected and frozen for later enzyme analysis. The catalytic activity of a pool of peptidases (dipeptidyl peptidase IV, prolyl endopeptidase, aminopeptidase A, aminopeptidase N, aspartyl aminopeptidase, aminopeptidase B, neutral endopeptidase, pyroglutamyl peptidase I, puromycin-sensitive aminopeptidase and cystinyl aminopeptidase) was measured fluorometrically. RESULTS: The activity of prolyl endopeptidase was higher in tonsillar hyperplasia and adenoid hyperplasia than in chronic tonsillitis. On the contrary, dipeptidyl peptidase IV activity was higher in chronic tonsillitis than in hypertrophic tissues. When data were stratified by age and gender, dipeptidyl peptidase IV was also found to be more active in adult and male chronic tonsillitis tissues. Inversely, dipeptidyl peptidase IV activity was higher in tissues of females with tonsillar hyperplasia. CONCLUSIONS: These data indicate the involvement of dipeptidyl peptidase IV and prolyl endopeptidase in the mechanisms underlying chronic tonsillitis, tonsillar hyperplasia and adenoid hyperplasia.