RESUMO
BACKGROUND: Staphylococcus aureus-derived enterotoxins (SEs) have been implicated in the pathogenesis of airway inflammatory diseases, especially nasal polyposis. However, the exact role of these molecules in the regulation of eicosanoid synthesis in this pathology remains unexplored. We studied the possible impact of SE-induced immune responses on the eicosanoid production in nasal polyp (NP) patients. METHODS: Tissue sample homogenates from NP patients, with (NP-SEs[+]) and without detectable IgE-antibodies to SEs (NP-SEs[-]; ImmunoCap system), were assayed for IL-5, myeloperoxidase, leukotriene CJD4/E4 (LTC4/D4/E4), LTB4, lipoxin A4, total IgE, and eosinophil cationic protein. RESULTS: Inflammatory makers, eicosanoids, and total IgE were significantly increased in NP-SEs(+) compared with NP-SEs(-) tissues, with the exception of myeloperoxidase, which was similar in both groups. Eicosanoid concentrations correlated to IL-5 and eosinophil cationic protein; however, only cys-leukotriene levels correlated with IgE-antibodies to SEs, independently of allergy and asthma. CONCLUSION: Eicosanoid synthesis is up-regulated in polyp tissue of patients with immune response to SEs and seems to be related to the inflammatory reaction induced by these enterotoxins.
Assuntos
Eicosanoides/metabolismo , Enterotoxinas/imunologia , Eosinófilos/imunologia , Pólipos Nasais/imunologia , Rinite/imunologia , Staphylococcus aureus/imunologia , Adulto , Biomarcadores/análise , Eicosanoides/análise , Feminino , Humanos , Imunoglobulina E/análise , Interleucina-5/análise , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/química , Pólipos Nasais/microbiologia , Rinite/microbiologiaRESUMO
BACKGROUND: This study analyzes the impact of Staphylococcus aureus enterotoxins (SAEs) and the inflammatory pattern in polyps from China. METHODS: Nasal tissue was obtained from 27 consecutive bilateral nasal polyps and 15 control patients and assayed for eotaxin, interleukin-5, soluble interleukin-2 receptor, transforming growth factor (TGF) beta, myeloperoxidase, eosinophil cationic protein, total IgE, and specific IgE to SAEs. Activated eosinophils were stained using EG2 antibodies in polyps from Chinese and comparative white patients. RESULTS: The number of EG2+ eosinophils was significantly lower in polyps from Chinese patients versus white patients. Chinese polyps showed significantly increased IgE and soluble interleukin-2 receptor versus control samples, whereas TGF-beta1 was significantly decreased. Ten of 27 samples in the polyp group versus 0 of 15 controls contained SAE-IgE (p < 0.01). TGF-beta1 was significantly down-regulated in SAE+ samples versus SAE- samples (p = 0.04). CONCLUSION: Nasal polyps from China are characterized by B- and T-cell activation, a minor eosinophilic inflammation compared with polyps from white subjects, and a decrease in TGF-beta1 in comparison with control inferior turbinate tissue. One-third of patients with polyps showed an IgE response to SAEs.
Assuntos
Enterotoxinas/imunologia , Pólipos Nasais/imunologia , Pólipos Nasais/microbiologia , Rinite/imunologia , Rinite/microbiologia , Staphylococcus aureus/imunologia , Adolescente , Adulto , Idoso , Povo Asiático , Linfócitos B/imunologia , China , Citocinas/análise , Proteínas Granulares de Eosinófilos/análise , Eosinófilos/química , Eosinófilos/imunologia , Feminino , Humanos , Imunoglobulina E/análise , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/química , Linfócitos T/imunologia , Fator de Crescimento Transformador beta1/análise , População BrancaRESUMO
BACKGROUND: Eicosanoid receptors are G-protein-coupled receptors playing an important immunomodulatory role in airway diseases. However, there is little information on the expression of these receptors and their link with eosinophilic inflammation in paranasal sinus diseases. We aimed with this study to investigate the tissue expression of leukotrienes and prostaglandin E2 receptors in chronic rhinosinusitis patients and the link of this regulation with eosinophilic inflammation. METHODS: Samples were prepared from nasal tissue of patients with chronic rhinosinusitis without nasal polyps (CRS, n = 11), with nasal polyps (CRS-NP, n = 13) and healthy subjects (Controls, n = 6). mRNA expression of CysLT1, CysLT2, BLT1, BLT2, E-prostanoid receptors (EP1, EP2, EP3, EP4) and sol-IL-5Ralpha was determined by real-time PCR. Concentrations of PGE2, LTC4/D4/E4, LTB4 and sol-IL-5Ralpha were determined by ELISA and of ECP by ImmunoCap. Protein expression and tissue localization of eicosanoid receptors and activated eosinophils were evaluated by immunohistochemistry. RESULTS: CysLT1 mRNA expression was significantly increased in CRS-NP compared to CRS and controls, and CRS compared to controls, whereas CysLT2 mRNA was enhanced in both CRS groups without differences between them. Levels of both receptors correlated to the number of activated eosinophils, sol-IL-5Ralpha, ECP and LTC4/D4/E4 concentrations in the disease groups. PGE2 protein concentrations and prostanoid receptors EP1 and EP3 were down-regulated in the CRS-NP tissue vs. CRS and controls, whereas EP2 and EP4 expression was enhanced in CRS and CRS-NP patients vs. controls. No differences in BLT receptors were observed between patients and controls. CONCLUSION: CyLTs receptors are up-regulated in nasal polyp tissue and their expression correlate with eosinophilic inflammation supporting previous results. Eicosanoid receptors mRNA pattern observed suggests that down-regulation of EP1 and EP3 in CRS-NP and up-regulation EP2 and EP4 in CRS and CRS-NP groups may have some role in the development of the diseases and their regulation may not be directly linked to eosinophil activation but involve post-transcriptional events mainly related to other inflammatory cell sources.
Assuntos
Eosinófilos/patologia , Receptores Eicosanoides/metabolismo , Rinite/metabolismo , Rinite/patologia , Sinusite/metabolismo , Sinusite/patologia , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Doença Crônica , Sistemas Computacionais , Eicosanoides/metabolismo , Feminino , Humanos , Imuno-Histoquímica/métodos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/complicações , Reação em Cadeia da Polimerase , Prostaglandinas/metabolismo , Isoformas de Proteínas/metabolismo , RNA Mensageiro/metabolismo , Receptores Eicosanoides/genética , Receptores de Leucotrienos/metabolismo , Receptores de Prostaglandina/metabolismo , Rinite/sangue , Rinite/complicações , Sinusite/sangue , Sinusite/complicações , Coloração e RotulagemRESUMO
BACKGROUND: Upper airway diseases and especially the aspirin hypersensitivity syndrome have been linked to changes in the arachidonic acid cascade; however, the specificity of these changes and their relation to inflammatory reactions in these diseases still remain controversial. OBJECTIVE: We aimed to study the tissue eicosanoid production in 3 subgroups of patients with chronic rhinosinusitis (CRS) and control subjects and to correlate it with the severity of inflammation and clinical manifestation of aspirin sensitivity. METHODS: Samples were prepared from sinonasal tissue of patients with CRS with (CRS-NP group, n = 13) and without nasal polyposis (CRS group, n = 11), sinonasal tissue of patients with nasal polyposis and aspirin sensitivity (CRS-ASNP group, n = 13), and normal nasal mucosa from healthy subjects (NM group, n = 8). Real-time PCR was applied for mRNA quantification of COX-2, 5-lipoxygenase, leukotriene C 4 synthase, and 15-lipoxygenase. Enzyme immunoassays were used to measure IL-5, eosinophil cationic protein, and eicosanoid (leukotriene [LT] C 4 , LTD 4 , and LTE 4 ; lipoxin A 4 ; and prostaglandin E 2 [PGE 2 ]) concentrations. RESULTS: COX-2 mRNA and PGE 2 concentrations were similar in the CRS and NM groups but significantly decreased in nasal polyp tissue, especially in the CRS-ASNP group. LTC 4 synthase, 5-lipoxygenase mRNA, LTC 4 , LTD 4 , and LTE 4 concentrations increased with disease severity among the patient groups. 15-Lipoxygenase and lipoxin A 4 concentrations were increased in all CRS groups compared with in the NM group but were significantly downregulated in the CRS-ASNP group when compared with the CRS-NP group. IL-5 and eosinophil cationic protein were increased in both groups of nasal polyp tissue compared with in the NM and CRS groups and correlated directly with LTC 4 , LTD 4 , and LTE 4 concentrations and inversely with PGE 2 concentrations. CONCLUSION: Changes of tissue eicosanoid metabolism do occur in CRS, even in the absence of clinical aspirin sensitivity, and these changes appear to be related to the severity of eosinophilic inflammation.
Assuntos
Leucotrienos/metabolismo , Lipoxinas/metabolismo , Pólipos Nasais/metabolismo , Prostaglandinas/metabolismo , Rinite/metabolismo , Sinusite/metabolismo , Adulto , Araquidonato 5-Lipoxigenase/genética , Araquidonato 5-Lipoxigenase/metabolismo , Doença Crônica , Ciclo-Oxigenase 2 , Eicosanoides/metabolismo , Proteína Catiônica de Eosinófilo/análise , Feminino , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Humanos , Interleucina-5/análise , Lipoxinas/análise , Masculino , Proteínas de Membrana , Pessoa de Meia-Idade , Mucosa Nasal/imunologia , Mucosa Nasal/metabolismo , Pólipos Nasais/complicações , Reação em Cadeia da Polimerase , Prostaglandina-Endoperóxido Sintases/genética , Prostaglandina-Endoperóxido Sintases/metabolismo , RNA Mensageiro/metabolismo , Rinite/complicações , Sinusite/complicaçõesRESUMO
BACKGROUND: Chronic rhinosinusitis (CRS) and nasal polyposis (NP) are histopathologically characterized by different gross morphological aspects. Transforming growth factor (TGF) beta1 plays an important role in tissue remodeling, which is poorly understood in chronic diseases of the sinuses. METHODS: The expression of TGF-beta1 was analyzed by enzyme-linked immunosorbent assay, quantitative reverse-transcription polymerase chain reaction, and immunohistochemistry in nasal tissue from controls (n = 6), CRS (n = 19), or NP (n = 19). RESULTS: CRS presented significantly higher concentrations of TGF-beta1 at protein (p = 0.0008) and mRNA levels (p = 0.025) when compared with NP samples. In CRS, TGF-beta1+ staining of the extracellular matrix was found abundantly and related to fibrosis. In contrast, no TGF-beta1 staining was found in the pseudocyst areas in NP. CONCLUSION: CRS was histologically characterized by fibrosis, which was reflected by a significantly higher expression of TGF-beta1 at RNA and protein levels when compared with NP. We show that TGF-beta1 expression is related to fibrosis, differentiating CRS without polyps from NP.
Assuntos
Rinite/fisiopatologia , Sinusite/fisiopatologia , Fator de Crescimento Transformador beta/fisiologia , Doença Crônica , Ensaio de Imunoadsorção Enzimática , Matriz Extracelular/metabolismo , Humanos , Imuno-Histoquímica , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rinite/metabolismo , Sinusite/metabolismo , Fator de Crescimento Transformador beta1Assuntos
Enterotoxinas/imunologia , Imunoglobulina E/imunologia , Pólipos Nasais/imunologia , Infecções Estafilocócicas/imunologia , Adulto , Aspirina/efeitos adversos , Aspirina/imunologia , Asma/complicações , Asma/imunologia , Doença Crônica , Hipersensibilidade a Drogas/complicações , Hipersensibilidade a Drogas/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/complicações , Rinite/complicações , Rinite/imunologia , Sinusite/complicações , Sinusite/imunologia , Staphylococcus aureus/imunologiaRESUMO
Functional endoscopic sinus surgery is considered the standard therapeutic procedure for chronic rhinosinusitis and nasal polyposis after failure of medical treatment. We tested the hypothesis that the healing outcome after surgery was correlated to the secretion profile of gelatinase-B (matrix metalloproteinase-9 [MMP-9]) and transforming growth factor-beta1 (TGF-beta1) in nasal fluid. We performed a prospective study in 36 patients bilaterally operated for chronic rhinosinusitits or nasal polyposis and the healing quality was evaluated until 6 months after surgery by standardized nasal endoscopy, using a visual analog scale. Before functional endoscopic sinus surgery and during the postoperative period, TGF-beta1 and MMP-9 in nasal secretions were measured by enzyme-linked immunosorbent assay. Both MMP-9 and TGF-beta1 showed a significant increase initially after surgery. The healing quality after 6 months was significantly and independently correlated to preoperative MMP-9 concentrations in nasal secretions (p = 0.03), initial disease (p = 0.03), and previous sinus surgery (p = 0.004). Furthermore, concentrations of MMP-9 were significantly lower in patients with good healing (visual analog scale < 3) from week 3 to month 6 compared to patients with poor healing. MMP-9 is the first objective factor suitable to predict and monitor the healing quality after sinus surgery, indicating MMP-9 as a possible therapeutic target.