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1.
BMC Infect Dis ; 19(1): 1036, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31818255

RESUMO

BACKGROUND: The cytokine gene polymorphism is important for the genetic susceptibility of infectious diseases. The aim of the present study was to investigate the relationship between TNF-α, IL-12, and IL-13 gene polymorphisms and predisposition to brucellosis. METHODS: In this study, 107 patients with brucellosis and 107 healthy individuals were evaluated. The SNPs of TNF-α)- 238 G/A) and IL-12 (+ 1188 A/C) were done by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and IL-13 genotyping at positions - 1512 (A/C) and - 1112 (C/T) were analysis by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) methods. IL-12, IL-13 and TNF-α serum levels were measured by a sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: IL-13 (-1512A/C) was associated with Brucellosis risk in dominant model (OR (95% CI) = 2.17 (1.02-4.62)), P-value = 0.041. However, there was no difference in allele and genotype frequencies of TNF-α)- 238 G/A), IL-12 (+ 1188 A/C) and IL-13 [- 1512 (A/C) and - 1112 (C/T)] between patients and controls. Serum levels of IL-12 and TNF-α were significantly more frequent in the patients than in the control groups. CONCLUSIONS: The IL-13 gene polymorphism can be used as a biomarker for detecting susceptibility to Brucella disease.


Assuntos
Brucelose/genética , Subunidade p35 da Interleucina-12/genética , Interleucina-13/genética , Fator de Necrose Tumoral alfa/genética , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Subunidade p35 da Interleucina-12/sangue , Interleucina-13/sangue , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem
2.
Scand J Immunol ; 90(5): e12820, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31486098

RESUMO

Allergens are the main trigger that enhances airway type 2 inflammation, and the epithelium is the first line of defense that reacts to its exposure. Therefore, epithelial-derived mediators, such as interleukin (IL)-25, IL-33, thymic stromal lymphopoietin (TSLP) and ezrin, may play a role as alarmins in IL-4/IL-13 signaling in allergic asthma (AA). We investigated the serum levels of IL-25, IL-33, TSLP, ezrin, IL-4 and IL-13, after bronchial challenge with Dermatophagoides pteronyssinus in patients with AA. We examined 18 subjects: nine steroid-free stable patients with AA sensitized to D. pteronyssinus and nine non-atopic healthy subjects (HS). Bronchial allergen challenge was performed using inhaled D. pteronyssinus allergen. IL-4, IL-13, IL-25, IL-33, TSLP and ezrin levels in serum were measured by ELISA at two time points - before and 24 hours after bronchial allergen challenge. The serum levels of IL-25, TSLP and ezrin did not differ between AA and HS groups at baseline. However, after allergen exposure, significant increases in serum levels of IL-25, TSLP and ezrin were observed only in patients with AA. The serum level of IL-33 at baseline was significantly higher in the AA group compared with HS, but the allergen challenge did not provoke an increase of this cytokine in any group. IL-4 and IL-13 levels were significantly higher at baseline in the AA group compared with HS and, after allergen exposure, were significantly increased in the AA group, with no effect on HS. Thus, the epithelial-derived mediators IL-25, TSLP and ezrin, via IL4/IL13 signaling, enhance type 2 inflammation after bronchial challenge with D. pteronyssinus in AA.


Assuntos
Antígenos de Dermatophagoides/imunologia , Asma/sangue , Asma/imunologia , Testes de Provocação Brônquica/métodos , Interleucina-13/sangue , Interleucina-4/sangue , Animais , Citocinas/sangue , Proteínas do Citoesqueleto/sangue , Dermatophagoides pteronyssinus/imunologia , Humanos , Interleucina-17/sangue , Interleucina-33/sangue , Transdução de Sinais/imunologia
3.
BMC Res Notes ; 12(1): 496, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399137

RESUMO

OBJECTIVE: We recently reported that curcumin supplementation in a metabolically (i.e., Western diet [WD]) and chemically (i.e., CCl4) induced female rat model of non-alcoholic steatohepatitis (NASH) was associated with lower liver pathology scores and molecular markers of inflammation. This occurred when curcumin was given during induction of disease (preventative arm; 8-week WD with or without curcumin [8WD + C vs. 8WD]) as well as when given after disease development (treatment arm; 12-week WD with or without curcumin during weeks 9-12 [12WD + C vs. 12WD]). Herein, we sought to extend our findings from that study by determining the effects of curcumin supplementation on cytokine/chemokine expression in serum collected from these same rats. RESULTS: 24 cytokines/chemokines were assayed. IL-2 (+ 80%) and IL-13 (+ 83%) were greater with curcumin supplementation in the prevention arm. IL-2 (+ 192%), IL-13 (+ 87%), IL-17A (+ 81%) and fractalkine (+ 121%) were higher while RANTES was lower (- 22%) with curcumin supplementation in the treatment arm (p < 0.05 for all). RANTES concentrations also correlated significantly with hepatic pathology scores of inflammation (r = 0.417, p = 0.008). Select serum cytokines/chemokines were affected with curcumin supplementation in this female rat model of NASH. Moreover, curcumin's effect(s) on RANTES and its association with liver disease pathogenesis and progression may warrant further investigation.


Assuntos
Anti-Inflamatórios/farmacologia , Curcumina/farmacologia , Suplementos Nutricionais , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/dietoterapia , Animais , Tetracloreto de Carbono/administração & dosagem , Quimiocina CCL5/sangue , Quimiocina CCL5/genética , Quimiocina CX3CL1/sangue , Quimiocina CX3CL1/genética , Dieta Ocidental/efeitos adversos , Modelos Animais de Doenças , Esquema de Medicação , Feminino , Humanos , Interleucina-13/sangue , Interleucina-13/genética , Interleucina-17/sangue , Interleucina-17/genética , Interleucina-2/sangue , Interleucina-2/genética , Fígado/metabolismo , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/genética , Ratos , Ratos Wistar , Resultado do Tratamento
4.
Mediators Inflamm ; 2019: 3140183, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31320835

RESUMO

To investigate the effect of ILC2s on Th2-type adaptive immunity during the acute exacerbation of chronic obstructive pulmonary disease (AECOPD), the study enrolled healthy people, stable COPD patients, and AECOPD patients. Flow cytometry was used to detect Th1, Th2, and ILC2 in the peripheral blood and CD80 and MHC II levels on ILC2. The mRNA levels of GATA3, RORα, and CRTH2 of ILC2s were detected by RT-PCR. In addition, ILC2s from the peripheral blood of AECOPD patients were cocultured with CD4+ T cells from the peripheral blood of healthy controls. Cytokine levels in serum of the three groups and the in vitro coculture supernatants were measured by ELISA. Compared with the stable COPD group or the healthy control group, Th2 in the peripheral blood of AECOPD group increased dramatically, inducing an increase of Th2/Th1 ratio in AECOPD patients. Meanwhile, the level of IL-4 in the serum of this group was also increased. However, we also detected ILC2s in the peripheral blood of the AECOPD group and found that it was also increased, alone with the increased GATA3, RORα, and CRTH2 mRNA levels. We also found that the CD80 and MHC II on ILC2 were significantly upregulated and the proportion of MHC II+ ILC2 cells was significantly positively correlated with the proportion of Th2 cells in AECOPD patients. To further demonstrate the effect of ILC2 on Th2 cells, we cocultured ILC2 with CD4+ T cells in vitro, which also showed a significant increase of Th2 ratio as well as Th2-associated cytokines IL-4, IL-5, and IL-13. However, we found that this effect of ILC2s on Th2 cells could be inhibited by the addition of anti-MHC II. The Th2/Th1 balance shifts to Th2 in AECOPD. ILC2s may function as APC by the upregulation of MHC II and regulate adaptive immunity shift to Th2-type response in AECOPD.


Assuntos
Imunidade Adaptativa , Linfócitos/citologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Células Th2/citologia , Idoso , Antígeno B7-1/sangue , Linfócitos T CD4-Positivos/citologia , Técnicas de Cocultura , Feminino , Humanos , Imunidade Inata , Interleucina-13/sangue , Interleucina-4/sangue , Interleucina-5/sangue , Complexo Principal de Histocompatibilidade , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/sangue , Células Th1/citologia
5.
J Diabetes Res ; 2019: 8512028, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31355294

RESUMO

Aim: To explore the role of group 2 innate lymphoid cells (ILC2s) in the pathogenesis of renal fibrosis in diabetic kidney disease (DKD). Methods: The proportion of ILC2s and the levels of Th2 cytokines (IL-4, IL-5, and IL-13) in the peripheral blood of normal control subjects (NC) or patients with type 2 diabetes mellitus (DM), early diabetic kidney disease (DKD1), or late diabetic kidney disease (DKD2) were analyzed by flow cytometry and ELISA. The expression of transforming growth factor-ß1 (TGF-ß1), fibronectin (FN), collagen1, IL-4Rα, and IL-13Rα1 in renal tubular epithelial cells (HK-2) induced by IL-4, IL-13, or high glucose was analyzed by ELISA or qPCR. Results: The proportion of ILC2s and the levels of IL-4, IL-5, and IL-13 were significantly increased in DKD patients and were positively correlated with the severity of DKD (P < 0.05). The expression of TGF-ß1, FN, and collagen1 was significantly upregulated in HK-2 cells induced by IL-4 or IL-13 (P < 0.05). Moreover, the IL-4Rα and IL-13Rα1 mRNA in HK2 cells were increased followed by high glucose alone or combined with IL-4 or IL-13, but the differences were not statistically significant (P > 0.05). However, compared with high-glucose stimulation alone, the expression of TGF-ß1, FN, and collagen1 was significantly increased in HK-2 cells induced by high glucose combined with IL-4 or IL-13 (P < 0.05). Conclusions: ILC2s may participate in renal fibrosis in DKD partly via TGF-ß1 signal pathway.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/sangue , Rim/patologia , Linfócitos/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta1/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Linhagem Celular , Colágeno/metabolismo , Diabetes Mellitus Tipo 2/complicações , Feminino , Fibrose , Humanos , Imunidade Inata/efeitos dos fármacos , Interleucina-13/sangue , Subunidade alfa1 de Receptor de Interleucina-13/sangue , Interleucina-4/sangue , Subunidade alfa de Receptor de Interleucina-4/sangue , Interleucina-5/sangue , Túbulos Renais Proximais/metabolismo , Masculino , Pessoa de Meia-Idade , Células Th2/citologia
6.
Bioanalysis ; 11(11): 1045-1054, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31251105

RESUMO

Aim: IL-13 is a biomarker of type 2 inflammation that plays a critical role in asthma. IL-13 is present in serum at subpicogram levels. Methods: Simoa HD-1 technology was evaluated for the detection and quantitation of IL-13 by using a commercially available IL-13 kit and compared with a Simoa HomeBrew (HB) IL-13 assay as well as Immunological Multi-Parameter Chip Technology (IMPACT), an internal Roche platform. Performance of the assays was evaluated based on preset criteria for sensitivity, standard curve and controls' accuracy and precision, reproducibility and parallelism of endogenous analyte in serum samples. Results: The Simoa platform offered high assay sensitivity for evaluation of IL-13. Conclusion: This paper discusses the challenges and considerations when evaluating kits and/or developing HomeBrew assays using ultrasensitive platforms.


Assuntos
Asma/sangue , Ensaio de Imunoadsorção Enzimática , Interleucina-13/sangue , Humanos
7.
Cancer Sci ; 110(7): 2156-2165, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31099450

RESUMO

The incidence of colorectal cancer (CRC) has been on the rise, which is linked to the increasing prevalence of obesity, based on global epidemiological evidence. Although chronic inflammation is implicated in tumor development, the mechanisms underlying obesity-associated CRC remain unknown. Here, we sought to identify the inflammatory cytokines and their roles in obesity-related colorectal tumorigenesis using cytokine array analyses in a mouse model. Colorectal tumorigenesis was induced through i.p. injection of azoxymethane once a week for 6 weeks in 6-week-old female WT C57Black/6J mice and the obesity diabetes model mouse KK/TaJcl, KK-Ay/TaJcl. The formation of aberrant crypt foci and colorectal tumors were more frequent in obese mice compared with WT mice, and both serum interleukin (IL)-13 and IL-13 receptor (R) expression in the normal intestinal mucosal epithelium were significantly increased in the obese mice. Furthermore, addition of IL-13 to a human CRC cell line and a human colon organoid culture altered the phenotype of intestinal epithelial cells. Knockdown experiments further revealed that IL-13Rα1 dominantly induced mucosal proliferation. Collectively, These results suggest an association between anti-inflammatory cytokines and colorectal carcinogenesis, and provide new research directions for cancer prevention strategies. In particular, inflammation provoked by obesity, notably by increased expression of the cytokine IL-13, could play an important role in the carcinogenesis of obesity-related CRC.


Assuntos
Focos de Criptas Aberrantes/patologia , Azoximetano/efeitos adversos , Neoplasias Colorretais/patologia , Interleucina-13/sangue , Obesidade/complicações , Regulação para Cima , Focos de Criptas Aberrantes/induzido quimicamente , Focos de Criptas Aberrantes/metabolismo , Animais , Azoximetano/administração & dosagem , Proliferação de Células , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/imunologia , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica , Células HT29 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/imunologia , Absorção Peritoneal , Receptores de Interleucina-13/sangue , Transdução de Sinais
8.
Bull Exp Biol Med ; 166(6): 770-773, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31028583

RESUMO

Plant lipid transfer proteins and homologues of the main birch pollen allergen Bet v 1 are involved in the development of allergic reactions of varying severity to plant foods and pollen. In this study, the sera from patients with tree and weed pollen allergies in the Moscow region were examined. The levels of IL-4, IL-5, IL-9, IL-10, IL-13, IL-17A, IFNγ, TNFα, and TNFß cytokines were determined in the sera of patients with specific IgE antibodies to Bet v 1 and Pru p 3 allergens. It was confirmed that patients with pollen allergy are often characterized by Th2 response of the immune system, though other mechanisms of allergy development occurred in some cases. The data obtained demonstrate the necessity of detailed analysis of the individual mechanism of allergic reactions and patient-centered approach to the personalized allergy treatment.


Assuntos
Antígenos de Plantas/imunologia , Proteínas de Transporte/imunologia , Imunoglobulina E/sangue , Proteínas de Plantas/imunologia , Rinite Alérgica Sazonal/sangue , Adulto , Antígenos de Plantas/química , Proteínas de Transporte/química , Estudos de Casos e Controles , Feminino , Expressão Gênica , Humanos , Imunoglobulina E/genética , Interferon gama/sangue , Interferon gama/imunologia , Interleucina-10/sangue , Interleucina-10/imunologia , Interleucina-13/sangue , Interleucina-13/imunologia , Interleucina-17/sangue , Interleucina-17/imunologia , Interleucina-4/sangue , Interleucina-4/imunologia , Interleucina-5/sangue , Interleucina-5/imunologia , Interleucina-9/sangue , Interleucina-9/imunologia , Linfotoxina-alfa/sangue , Linfotoxina-alfa/imunologia , Masculino , Pessoa de Meia-Idade , Moscou , Proteínas de Plantas/química , Medicina de Precisão , Proteínas Recombinantes/química , Proteínas Recombinantes/imunologia , Rinite Alérgica Sazonal/genética , Rinite Alérgica Sazonal/imunologia , Rinite Alérgica Sazonal/fisiopatologia , Células Th1/imunologia , Células Th17/imunologia , Células Th2/imunologia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/imunologia
9.
Mediators Inflamm ; 2019: 9483647, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31011288

RESUMO

CD4+ T-cells play crucial roles in the injured heart. However, the way in which different CD4+ T subtypes function in the myocardial infarction/reperfusion (MI/R) heart is still poorly understood. We aimed to detect the dynamic profile of distinct CD4+ subpopulation-associated cytokines/chemokines by relying on a closed-chest acute murine MI/R model. The protein levels of 26 CD4+ T-cell-associated cytokines/chemokines were detected in the heart tissues and serum of mice at day 7 and day 14 post-MI/R or sham surgery. The mRNA levels of IL-4, IL-6, IL-13, IL-27, MIP-1ß, MCP-3, and GRO-α were measured in blood mononuclear cells. The protein levels of IL-4, IL-6, IL-13, IL-27, MIP-1ß, MCP-3, and GRO-α increased in both injured heart tissues and serum, while IFN-γ, IL-12P70, IL-2, IL-1ß, IL-18, TNF-α, IL-5, IL-9, IL-17A, IL-23, IL-10, eotaxin, MIP-1α, RANTES, MCP-1, and MIP-2 increased only in MI/R heart tissues in the day 7 and day 14 groups compared to the sham group. In serum, the IFN-γ, IL-23, and IL-10 levels were downregulated in the MI/R model at both day 7 and day 14 compared to the sham. Compared with the protein expressions in injured heart tissues at day 7, IFN-γ, IL-12P70, IL-2, IL-18, TNF-α, IL-6, IL-4, IL-5, IL-9, IL-17A, IL-23, IL-27, IL-10, eotaxin, IP-10, RANTES, MCP-1, MCP-3, and GRO-α were reduced, while IL-1ß and MIP-2 were elevated at day 14. IL-13 and MIP-1ß showed higher levels in the MI/R serum at day 14 than at day 7. mRNA levels of IL-4, IL-6, IL-13, and IL-27 were increased in the day 7 group compared to the sham, while MIP-1ß, MCP-3, and GRO-α mRNA levels showed no significant difference between the MI/R and sham groups in blood mononuclear cells. Multiple CD4+ T-cell-associated cytokines/chemokines were upregulated in the MI/R hearts at the chronic stage. These results provided important evidence necessary for developing future immunomodulatory therapies after MI/R.


Assuntos
Linfócitos T CD4-Positivos/metabolismo , Quimiocinas/metabolismo , Citocinas/metabolismo , Infarto do Miocárdio/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Animais , Quimiocina CCL3/sangue , Quimiocina CCL3/metabolismo , Interleucina-10/sangue , Interleucina-10/metabolismo , Interleucina-13/sangue , Interleucina-13/metabolismo , Interleucina-4/sangue , Interleucina-4/metabolismo , Interleucina-6/sangue , Interleucina-6/metabolismo , Leucócitos Mononucleares/metabolismo , Masculino , Camundongos , Infarto do Miocárdio/sangue , Traumatismo por Reperfusão Miocárdica/sangue
10.
Clin Lab ; 65(3)2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30868866

RESUMO

BACKGROUND: In the present study, we mainly focused on miR-98-5p, which is shown to be dysregulated in various diseases. However, whether miR-98-5p is increased in the serum of asthma patients has never been explored. METHODS: The levels of miR-98-5p and IL-13 were determined in the serum of bronchial asthma children. ROC analysis was carried out to evaluate whether miR-98-5p could be used as a potential biomarker for children with bronchial asthma. RESULTS: The current study showed that the relative expression level of miR-98-5p in the asthmatic remission group and asthmatic acute group was significantly lower than that in the healthy control group, and the relative expression level of miR-98-5p in the asthmatic acute group was significantly lower than that in the asthmatic remission group. In children with acute asthma attacks, the levels of miR-98-5p in the moderate group and severe group were significantly lower than those in the mild group, and those in the severe group were significantly lower than those in the moderate group. Furthermore, the serum IL-13 levels in the asthma remission group and acute asthma group were significantly higher than those in the healthy control group, and the serum IL-13 levels in acute asthma group were significantly higher than those in asthma remission group. CONCLUSIONS: In summary, the current study suggests that miR-98-5p may affect the occurrence and development of bronchial asthma in children via affecting the expression of IL-13.


Assuntos
Asma/sangue , Interleucina-13/sangue , MicroRNAs/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Células HEK293 , Humanos , Masculino
11.
J Gastroenterol Hepatol ; 34(4): 764-775, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30695096

RESUMO

BACKGROUND AND AIM: Hepatitis delta virus (HDV) infection is the most rapidly progressive chronic viral hepatitis. Little is understood about the immune responses to HDV. This study aims to characterize the systemic immune environments of hepatitis B virus (HBV) and HDV patients at various disease stages. METHODS: A total of 129 subjects were evaluated: 53 HBV, 43 HDV, and 33 healthy controls. HBV and HDV subjects were categorized by aspartate aminotransferase to platelet ratio index (APRI) into mild (APRI < 0.5), moderate, and severe (APRI > 1.0). Serum cytokines and immune markers were assessed at a single treatment-naïve time-point. RESULTS: Type 1 cytokines are elevated in both HBV and HDV. Both groups show higher tumor necrosis factor-α (TNF-α), interleukin (IL)-12p40, and C-X-C motif chemokine ligand 9 when compared with controls (all P < 0.05). However, only HBV group displayed elevated γ-interferon compared with controls. Type 2 cytokines are elevated in HBV. HBV group shows higher IL-4, IL-13, and C-C motif chemokine ligand (CCL) 26 compared with healthy controls and HDV. Chemokines CCL2 and CCL13 are lower in HDV. When assessing ratios, HDV displays higher γ-interferon/IL-4, TNF-α/IL-4, and TNF-α/IL-13 ratios than HBV and controls. CONCLUSION: Hepatitis B virus and HDV subjects show similarly elevated type 1 cytokines. HDV subjects display relatively lower type 2 cytokines. These differences in the systemic immune environments, particularly the predominance of type 1 responses, may contribute to the comparatively rapid progression of HDV disease. Characterization of the imbalance in type 1 and type 2 immunity unique HDV has the potential to provide immunological insights for designing therapeutic targets in HDV-associated disease progression.


Assuntos
Citocinas/sangue , Vírus da Hepatite B/imunologia , Hepatite B/imunologia , Hepatite D/imunologia , Vírus Delta da Hepatite/imunologia , Adulto , Idoso , Quimiocina CCL2/sangue , Quimiocinas CXC/sangue , Progressão da Doença , Feminino , Hepatite D/terapia , Humanos , Interferon gama/sangue , Interleucina-12/sangue , Interleucina-13/sangue , Interleucina-4/sangue , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Fator de Necrose Tumoral alfa/sangue
12.
Support Care Cancer ; 27(9): 3301-3310, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30612237

RESUMO

OBJECTIVE: Benefits of social support (SS) during cancer survivorship are complex. This study examines change in SS over time in cervical cancer (CXCA) survivors who have completed definitive treatment and how changing SS impacts quality of life (QOL) and T-helper type 2 (Th2) cytokines. METHODS: We conducted a randomized trial in 204 CXCA survivors to test if psychosocial telephone counseling (PTC) could improve QOL compared to usual care (UC). Although PTC did not target SS, data were collected at baseline, 4 and 9 months post-enrollment using the Medical Outcomes Survey Social Support scale. Biospecimens were collected to investigate associations with patient-reported outcomes. Data were analyzed using multivariate linear models and stepwise regression. RESULTS: Participants' mean age was 43. PTC participants experienced increasing SS compared to UC at 4 months (PTC-UC = 5.1; p = 0.055) and 9 months (PTC-UC = 6.0; p = 0.046). Higher baseline SS and increasing SS were independently associated with improved QOL at 4 and 9 months after adjusting for patient characteristics (p < 0.05). Differences between study arms were not statistically significant. Improvements in QOL at 4 months were observed with increases in emotional/informational and tangible SS. Increasing SS predicted significant longitudinal decreases in IL-4 and IL-13 at 4 months that were larger in the PTC arm (interactions p = 0.041 and p = 0.057, respectively). CONCLUSION: Improved SS was significantly associated with improved QOL independent of patient characteristics and study arm. Decreasing Th2 cytokines with increasing SS and QOL are consistent with a biobehavioral paradigm in which modulation of the chronic stress response is associated with shifts in immune stance.


Assuntos
Sobreviventes de Câncer/psicologia , Citocinas/sangue , Qualidade de Vida/psicologia , Apoio Social , Sobrevivência , Neoplasias do Colo do Útero/psicologia , Adulto , Aconselhamento , Feminino , Humanos , Interleucina-13/sangue , Interleucina-4/sangue , Masculino , Pessoa de Meia-Idade , Telefone , Células Th2/imunologia , Neoplasias do Colo do Útero/sangue
13.
Am J Respir Crit Care Med ; 199(4): 496-507, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30290132

RESUMO

RATIONALE: Bronchial epithelial cell damage occurs in patients with bronchial asthma. Ezrin, a membrane-cytoskeleton protein, maintains cellular morphology and intercellular adhesion and protects the barrier function of epithelial cells. OBJECTIVES: To study the role of ezrin in bronchial epithelial cells injury and correlate its expression with asthma severity. METHODS: Levels of ezrin were measured in exhaled breath condensate (EBC) and serum in patients with asthma and BAL fluid (BALF) from a mouse model of asthma by ELISA. The regulation of IL-13 on ezrin protein levels was studied in primary bronchial epithelial cells. Ezrin knockdown using shRNA was studied in human bronchial epithelial 16HBE cells. MEASUREMENTS AND MAIN RESULTS: Ezrin levels were decreased in asthmatic EBC (92.7 ± 34.99 vs. 150.5 ± 10.22 pg/ml, P < 0.0001) and serum (700.7 ± 55.59 vs. 279.2 ± 25.83 pg/ml, P < 0.0001) compared with normal subjects. Levels were much lower in uncontrolled (P < 0.001) and partly controlled patients (P < 0.01) compared with well-controlled subjects. EBC and serum ezrin levels correlated with lung function in patients with asthma and serum ezrin levels were negatively correlated with serum IL-13 and periostin. IL-13-induced downregulation of ezrin expression in primary bronchial epithelial cells was significantly attenuated by the Janus tyrosine kinase 2 inhibitor, TG101348. Ezrin knockdown changed 16HBE cell morphology, enlarged intercellular spaces, and increased their permeability. Ezrin expression was decreased in the lung tissue and BALF of "asthmatic" mice and negatively correlated with BALF IL-13 level. CONCLUSIONS: Ezrin downregulation is associated with IL-13-induced epithelial damage and might be a potential biomarker of asthma control.


Assuntos
Asma/patologia , Proteínas do Citoesqueleto/análise , Mucosa Respiratória/patologia , Animais , Asma/sangue , Biomarcadores/análise , Biomarcadores/sangue , Brônquios/patologia , Líquido da Lavagem Broncoalveolar/química , Estudos de Casos e Controles , Moléculas de Adesão Celular/sangue , Proteínas do Citoesqueleto/sangue , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interleucina-13/sangue , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Testes de Função Respiratória
14.
J Ethnopharmacol ; 231: 275-282, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30496840

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Yan-Hou-Qing (YHQ), a Chinese medicine formula containing fourteen kinds of materials, has been designed for pharyngitis and cough treatment in Oriental medicine. In the present study, the anti-allergic effects and underlying mechanisms of YHQ in inhibition of airway hyper responsiveness (AHR) was explored in an ovalbumin (OVA)-induced allergic asthma mouse model. MATERIALS AND METHODS: BALB/c mice were sensitized by OVA and cholera toxin (CT) and challenged with OVA intranasally to induce allergic asthma mouse model. YHQ (200 mg/kg) was orally administered for 3 weeks from week-2 after OVA sensitization. The AHR and histological changes of lung tissues were evaluated by whole-body barometric plethysmography analysis and hematoxylin and eosin (H&E) staining, respectively. The serum concentration of OVA-specific IgE and T helper 2 (Th2) cytokines (IL-4 and IL-13) were determined by enzyme-linked immune sorbent assay (ELISA). Flow cytometry was performed to evaluate the percentage of CD4+CD25+Foxp3+ regulatory T cells (Treg) in the spleen. RESULTS: The elevated AHR responses, heavier inflammatory cell infiltration and Th2 cytokines in allergic asthma group indicated Ovalbumin-induced asthmatic mouse models were built successfully. Compared to allergic asthma group, OVA-induced AHR responses and eosinophil infiltration in lung were improved significantly, and the productions of OVA-specific IgE and Th2 cytokines, IL-4 and IL-13, in the serum were also reduced dramatically after the treatment of YHQ. Moreover, YHQ treatment significantly increased the percentage of CD4+CD25+Foxp3+ Treg in OVA-induced allergic asthma mouse model. CONCLUSIONS: YHQ improves the allergic asthma related symptoms via promotion of CD4+CD25+Foxp3+ Treg and suppression of Th2 responses in mouse model, suggesting YHQ can be used as a potent agent to alleviate allergic asthma related symptoms.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Linfócitos T Reguladores/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Alérgenos , Animais , Antiasmáticos/farmacologia , Asma/sangue , Asma/imunologia , Toxina da Cólera , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Imunoglobulina E/sangue , Interleucina-13/sangue , Interleucina-4/sangue , Camundongos Endogâmicos BALB C , Ovalbumina , Linfócitos T Reguladores/imunologia , Células Th2/imunologia
15.
Eur Arch Otorhinolaryngol ; 276(2): 407-415, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30488351

RESUMO

PURPOSE: Allergic rhinitis is an immunoglobulin-E (Ig-E)-mediated response driven by type 2 helper T cells. Hesperidin and thymol are biological agents that possess antioxidant and anti-inflammatory characteristics. The purpose of this study was to investigate the effects of hesperidin and thymol in rats with ovalbumin-induced allergic rhinitis. METHODS: Thirty adult Sprague-Dawley rats were randomly assigned into five groups, each containing six animals. The first group constituted the negative control group, while the remaining groups were exposed to an ovalbumin-induced model of allergic rhinitis. In the provocation stage, 4 mL/kg saline was administered to the positive control group, 10 mg/kg desloratadine to the reference group, 100 mg/kg hesperidin to the hesperidin group, and 20 mg/kg thymol to the thymol group, all by gastric lavage for 7 days. Nasal symptoms were scored on day 22. Rats were then sacrificed, and intracardiac blood specimens were collected to measure plasma total Ig-E, IL-5, IL-13, total antioxidant capacity (TAC), and total oxidant status (TOS) levels. Nasal tissues were extracted for histopathological and immunochemical examination. RESULTS: Nasal symptom scores were highest in the positive control group, while hesperidin and thymol ameliorated these symptoms to the same extent as desloratadine. Ig-E, IL-5, IL-13, and TOS levels increased, while TAC levels decreased significantly in the allergic rhinitis group compared to the other groups. Significant improvement in these parameters was observed in both the hesperidin and thymol groups. At histopathological and immunohistochemical examination of the nasal cavity, severe allergic inflammation and severe TNF-α expression was determined in rats from the allergic rhinitis group. Mild inflammatory changes and mild TNF-α expression were observed in all three treatment groups. CONCLUSION: Both hesperidin and thymol were effective in suppressing allergic symptoms and inflammation in the treatment of allergic rhinitis.


Assuntos
Hesperidina/farmacologia , Rinite Alérgica/tratamento farmacológico , Timol/farmacologia , Animais , Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Modelos Animais de Doenças , Imunoglobulina E/sangue , Inflamação/patologia , Interleucina-13/sangue , Interleucina-5/sangue , Cavidade Nasal/metabolismo , Cavidade Nasal/patologia , Ovalbumina/efeitos adversos , Oxidantes/metabolismo , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
16.
Iran J Immunol ; 15(4): 302-308, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30593744

RESUMO

BACKGROUND: Bacteremia and sepsis are associated with high mortality, increased hospital stays, and associated costs, especially in trauma patients. Sepsis is a fatal immunological disorder and its pathophysiology is still poorly understood. OBJECTIVE: To ascertain the role of T-helper lymphocyte-related inflammatory serum cytokines in trauma patients with blood culture positive with Gram-negative bacteria. METHODS: Peripheral blood samples (5 ml) were collected from 40 trauma patients on the day of obtaining positive blood culture (i.e., day 0), followed by an appropriate antimicrobial treatment and sample acquisition on day 4 and only once from 40 age-matched healthy controls. Bead-based cytometric analysis was used to quantify extracellular levels of 16 serum cytokines. The cytokine profiles were compared with those in healthy controls and then correlated to clinical outcomes. RESULTS: A total of 40 patients were enrolled during the study period. Of these, 24 patients (60%) were discharged while 16 (40%) had a fatal outcome. Statistically significant elevated levels of serum IL-6, IFN-γ, TNF-α, IL-17A, IL-17F, and IL-4 were observed in septic patients, while lowered IL-13 levels correlated significantly with a favorable outcome. CONCLUSION: Sepsis following trauma elicits a heightened immune response in the body and provokes the production of a diverse array of cytokines that is both pro-inflammatory and anti-inflammatory. However, the unique cytokine profile of septic trauma patients is still not well understood.


Assuntos
Infecções por Acinetobacter/imunologia , Acinetobacter baumannii/fisiologia , Bacteriemia/imunologia , Interleucina-13/sangue , Traumatismo Múltiplo/imunologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Adolescente , Adulto , Bacteriemia/mortalidade , Biomarcadores/sangue , Estudos de Coortes , Citocinas/sangue , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Traumatismo Múltiplo/mortalidade , Estudos Prospectivos , Análise de Sobrevida , Adulto Jovem
17.
Eur Rev Med Pharmacol Sci ; 22(23): 8076-8083, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30556842

RESUMO

OBJECTIVE: To investigate the potential effect of miR-487b/IL-33-ST2 axis on the pathology of allergic rhinitis (AR) and the relevant mechanism. PATIENTS AND METHODS: The expression level of interleukin-33 (IL-33), a homolog of sulfotransferase (ST2), and miR-487b were detected in patients with or without allergic rhinitis. Luciferase assay was performed to evaluate the interaction between miR-487b and IL-33, and the effects of miR-487b/IL-33-ST2 axis on allergic rhinitis mice were determined by established allergic rhinitis model in mice by ovalbumin (OVA). The levels of OVA-specific immunoglobulin E (Ig-E), proinflammatory cytokines (IL-4, IL-5, and IL-13), and pathological alterations were detected. RESULTS: The level of IL-33 and its specific ligand ST2 were found increased in allergic rhinitis patients while miR-487b expression level was markedly repressed. To confirm whether miR-487b has a regulation effect on IL-33, we checked it in three publicly available algorithms, TargetScan, miRDB, and microRNA. We found that IL-33 is a direct target of miR-487b, and Luciferase assays confirmed our hypothesis, the subsequent experiments showed that up-regulation of miR-487b could inhibit expression of IL-33 and ST2, resulting in the decrease of the immunoglobulin E (Ig-E), proinflammatory cytokines and mitigation of pathological alterations. CONCLUSIONS: Our research discovered the suppressor function of miR-487b in allergic rhinitis and revealed that miR-487b/IL-33-ST2 axis may be a potential therapeutic target for the treatment of allergic rhinitis.


Assuntos
Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Interleucina-33/metabolismo , MicroRNAs/metabolismo , Mucosa Nasal/metabolismo , Rinite Alérgica/metabolismo , Animais , Estudos de Casos e Controles , Modelos Animais de Doenças , Células HEK293 , Humanos , Imunoglobulina E/sangue , Proteína 1 Semelhante a Receptor de Interleucina-1/genética , Interleucina-13/sangue , Interleucina-33/genética , Interleucina-4/sangue , Interleucina-5/sangue , Masculino , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Mucosa Nasal/imunologia , Rinite Alérgica/genética , Rinite Alérgica/imunologia , Transdução de Sinais
18.
Indian J Med Res ; 148(2): 159-168, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30381539

RESUMO

Background & objectives: High expression of arginase gene and its elevated level in serum and bronchial lavage reported in animal models indicated an association with the pathogenesis of asthma. This study was undertaken to assess the serum arginase activity in symptomatic asthma patients and healthy controls and to correlate it with cytokine levels [interleukin (IL)-4 and IL-13] and arginase I (ARG1) gene polymorphism. Methods: Asthma was confirmed by lung function test according to the GINA guidelines in patients attending Allergy and Pulmonology Clinic, Bhagwan Mahavir Hospital and Research Centre, Hyderabad, India, a tertiary care centre, during 2013-2015. Serum arginase was analyzed using a biochemical assay, total IgE and cytokine levels by enzyme-linked immunosorbent assay and genotyping of ARG1 for single-nucleotide polymorphisms (SNPs) rs2781666 and rs60389358 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: There was a significant two-fold elevation in the arginase activity in asthmatics as compared to healthy controls which correlated with disease severity. Non-atopic asthmatics showed elevated activity of arginase compared to atopics, indicating its possible role in intrinsic asthma. Levels of serum IL-13 and IL-4 were significantly high in asthma group which correlated with disease severity that was assessed by spirometry. A positive correlation was observed between arginase activity and IL-13 concentration. Genetic analysis of ARG1 SNPs revealed that rs2781666 G/T genotype, T allele and C-T haplotype (rs60389358 and rs2781666) were associated with susceptibility to asthma. Interpretation & conclusions: This study indicated that high arginase activity and IL-13 concentration in the serum and ARG1 rs2781666 G/T genotype might increase the risk of asthma in susceptible population. Further studies need to be done with a large sample to confirm these findings.


Assuntos
Arginase/genética , Asma/genética , Predisposição Genética para Doença , Interleucina-13/genética , Adolescente , Adulto , Arginase/sangue , Asma/sangue , Asma/fisiopatologia , Feminino , Estudos de Associação Genética , Genótipo , Haplótipos , Humanos , Interleucina-13/sangue , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Adulto Jovem
20.
Immunol Allergy Clin North Am ; 38(4): 611-628, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30342583

RESUMO

Periostin and dipeptidyl peptidase-4 (DPP-4) are proteins induced by type 2 cytokines interleukin (IL)-4 and IL-13 and show increased expression in asthma and diseases with type 2 inflammation, including atopic dermatitis and chronic rhinosinusitis. Both proteins can also be induced by other stimuli, such as profibrotic factors, which may confound their specificity as biomarkers of IL-13 pathway activation and type 2-driven disease. DPP-4 is important in glucose metabolism; therefore, serum concentrations may be confounded by the presence of concomitant metabolic disease. This review evaluates the potential of these biomarkers for anti-IL-13-directed therapy in asthma and diseases with type 2 inflammation.


Assuntos
Moléculas de Adesão Celular/sangue , Dipeptidil Peptidase 4/sangue , Hipersensibilidade/sangue , Hipersensibilidade/imunologia , Interleucina-13/sangue , Interleucina-13/imunologia , Asma/sangue , Asma/imunologia , Biomarcadores/sangue , Moléculas de Adesão Celular/imunologia , Dipeptidil Peptidase 4/imunologia , Humanos
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