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Abstract Background Interleukin-17 (IL-17) family plays a role in the pathogenesis of knee osteoarthritis (KOA) by contributing to the inflammatory and destructive processes in the affected joint. This study aimed to measure levels of IL-17 A and IL-25 (IL-17E) in serum of KOA patients and determine their roles in the disease severity of patients. Methods In this, 34 patients with KOA and 30 age and sex-matched healthy subjects (HS) were enrolled. Patients were categorized based on their Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Visual Analog Scale (VAS), and Body Mass Index (BMI) scores. The enzyme-linked immunosorbent assay (ELISA) technique was employed to measure serum levels of IL-17 A and IL-25. Results Level of IL-25 was significantly higher (P < 0.0001) in the KOA subjects than HS. IL-17 A level was significantly higher in KOA cases with WOMAC < 40 (P < 0.0001) in comparison to HS. IL-25 level was significantly higher in the KOA cases with WOMAC < 40 (P < 0.0001) and with WOMAC ≥ 40 (P < 0.0001) compared to HS. IL-17 A concentration was significantly higher in the KOA cases with VAS < 5 (P < 0.0001) compared to HS. IL-25 level was significantly higher in the KOA cases with VAS < 5 (P < 0.0001) and with VAS ≥ 5 (P < 0.0001) in comparison to HS. KOA patients with BMI ≥ 30 had significantly higher IL-17 A and IL-25 concentration in comparison to HS. Conclusions The serum level of IL-25 in KOA patients is increased probably due to negative controlling feedback on inflammatory responses, which can be associated with obesity and disease activity.
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Epidermal barrier defects and immune abnormalities are the main pathophysiological changes in the development of atopic dermatitis (AD) . Skin keratinocytes can release a variety of inflammatory factors and mediators under the treatment with various harmful factors. Three epithelium-derived cytokines interleukin (IL) -33, IL-25 and thymic stromal lymphopoietin are considered to be effective inducers of Th2 immune response in skin or mucosal barrier, which can activate immune cells, cause the secretion of Th2 cytokines, enhance the Th2 immune response, and participate in the occurrence and development of AD. This review focuses on the role of the above 3 epithelium-derived cytokines in the pathogenesis of AD.
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Objective@#To investigate the regulation of IL-25 on type Ⅱ innate lymphoid cells (ILC2s) activation in the pathogenesis of allergic fungal rhinosinusitis (AFRS).@*Methods@#Nasal mucosa tissues were collected from 16 AFRS patients and 12 patients, who underwent nasal endoscopic surgery for cerebrospinal rhinorrhea or skull base benign tumor during the period from June 2016 to June 2017 in Department of Rhinology, the First Affiliated Hospital of Zhengzhou University. Firstly, flow cytometry was used to detect ILC2s in nasal mucosa of both groups. Secondly, the expression of IL-25, IL-5 and IL-13 in nasal mucosa was detected by immunofluorescence and/or Western Blot assay. Finally, fungal extracts, IL-25 and glucocorticoids were used to stimulate nasal mucosal epithelial cells and tissues in vitro respectively to detect the regulatory effect of IL-25 on ILC2s. SPSS 16.0 software was used to analyze the data.@*Results@#The prevalence of ILC2s in nasal tissues was higher in patients with AFRS than those of the control group ((3.85±1.52)%(Mean±SD) vs (0.32±0.10)%, U=9.00, P<0.05). There was a positive correlation between the prevalence of ILC2s and the number of eosinophils in nasal mucosa of patients with ARFS (r=0.80, P<0.05). The expression of IL-25, IL-5 and IL-13 in nasal mucosa epithelium of AFRS group was significantly higher than that of the control group (0.49±0.13 vs 0.23±0.09, 0.23±0.05 vs 0.10±0.04, 0.31±0.08 vs 0.14±0.07, t value was 5.90, 7.21, 5.69, respectively, all P<0.05). Fungal stimulation enhanced the expression of IL-25 protein in nasal epithelial cells of both groups (0.67±0.19 vs 0.25±0.12 (AFRS group), 0.62±0.17 vs 0.27±0.16 (control group), q value was 8.65, 9.26, respectively, all P<0.05). In the IL-25 stimulated nasal mucosa at a concentration of 1, 10 and 100 ng/ml, the expression level of retinoid acid-related orphan receptor α (RORα) mRNA was 2.07±1.53, 5.06±0.93, 7.38±2.30, respectively; the expression level of GATA binding protein 3 (GATA3) mRNA was 3.58±1.29, 6.14±1.55, 7.64±2.28, respectively; the expression level of IL-5 protein was 0.21±0.06, 0.32±0.06, 0.38±0.10, respectively; the expression level of IL-13 was 0.52±0.13, 0.69±0.22, 0.82±0.21, respectively, which were significantly higher than that in the unstimulated nasal mucosa (1.00±0.00, 1.00±0.00, 0.11±0.05, 0.35±0.15, F value was 63.45, 59.27, 49.35, 20.20, respectively, all P<0.05). The up-regulation could be inhibited by dexamethasone (F value was 89.20, 92.47, 99.63, 49.82, respectively, all P<0.05).@*Conclusions@#Epithelial-derived IL-25 up-regulates the expression of IRC2s-dependent transcription factors RORα and GATA3 mRNA, which are positively correlated with elevated IL-13 and IL-5 expression levels in tissues, may be involved in AFRS inflammatory response, and are inhibited by glucocorticoids.
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Objective To study the function of interleukin (IL)-25 for rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) differentiation as well as on the expression of extracellular regulating protein kinase (ERK) and matrix metalloproteinases-3 (MMP-3).Methods The differences on ERK1/2 and MMP-3 protein levels were tested in RA-FLS of RA patients and healthy controls,then IL-17A (10 ng/ml) was tested when the RA-FLS were co-stimulated with different concentrations of IL-25 (0.01,0.1,1 and 10 ng/ml) and IL-17A(10 ng/ml) for 24 hours respectively.The expression of ERK1/2 and MMP-3 protein was detected by the Western blot.T test was used for the comparison between different groups.Results The expression of ERK1/2 (1.71±0.17) and MMP-3 (0.50±0.13) proteins in RA-FLS was higher than the healthy controls (0.50±0.15,0.17±0.05) (t=-9.13,P＜0.01 and t=-4.10,P＜0.05),after stimulated with IL-17A,the expression of ERK1/2 (0.77±0.22) and MMP-3 (0.59±0.13) proteins in RA-FLS were increased compared with the untreated groups (0.18±0.35,0.04±0.03) (t=-4.69,P＜0.01 and t=-7.47,P＜0.01).With increase of the concentration on IL-25,the level of ERK1/2 (0.54±0.26,0.48±0.18,0.48±0.23,0.23±0.06) and MMP-3 (0.58±0.09,0.59±0.14,0.21±0.04,0.04±0.02) in RA-FLS which were stimulated by IL-17A was decreased slowly (t=4.22,P＜0.05 and t=4.95,P＜0.01 and t=7.47,P＜0.01).Conclusion IL-25 can inhibit the stimulation of IL-17A on ERK1/2 and MMP-3 fractionally,which implies that it may take part in the development of RA through this pathway and may be a target for the RA treatment.
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Objective@#Allergic airway diseases (AADs) are a group of heterogeneous disease mediated by T-helper type 2 (Th2) immune response and characterized with airway inflammation and remodeling, including allergic asthma, allergic rhinitis, and chronic rhinosinusitis with allergic background. This review aimed to discuss the abnormal epithelial-mesenchymal crosstalk in the pathogenesis of AADs.@*Data Sources@#Articles referred in this review were collected from the database of PubMed published in English up to January 2018.@*Study Selection@#We had done a literature search using the following terms "allergic airway disease OR asthma OR allergic rhinitis OR chronic sinusitis AND IL-25 OR IL-33 OR thymic stromal lymphopoietin OR fibrocyte". Related original or review articles were included and carefully analyzed.@*Results@#It is now believed that abnormal epithelial-mesenchymal crosstalk underlies the pathogenesis of AADs. However, the key regulatory factors and molecular events involved in this process still remain unclear. Epithelium-derived triple cytokines, including interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP), are shown to act on various target cells and promote the Th2 immune response. Circulating fibrocyte is an important mesenchymal cell that can mediate tissue remodeling. We previously found that IL-25-circulating fibrocyte axis was significantly upregulated in patients with asthma, which may greatly contribute to asthmatic airway inflammation and remodeling.@*Conclusions@#In view of the redundancy of cytokines and "united airway" theory, we propose a new concept that IL-25/IL-33/TSLP-fibrocyte axis may play a vital role in the abnormal epithelial-mesenchymal crosstalk in some endotypes of AADs. This novel idea will guide potential new intervention schema for the common treatment of AADs sharing common pathogenesis in the future.
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Humans , Asthma , Metabolism , Cytokines , Physiology , Interleukin-17 , Physiology , Interleukin-33 , PhysiologyABSTRACT
Objective To study the molecular mechanism of interleukin 25 (IL-25)expression in the lung of asthmatic rats.Methods The expressions of IL-25 mRNA and protein in the lungs were detected by Real-time PCR and ELISA,respectively.The levels of IL-25 mRNA and protein were detected by ovalbumin (OVA)in human bronchial epithelial cells.And the transcription factors that regulate IL-2 5 expression were explored through site prediction.Results The expressions of IL-25 mRNA and protein in the lung of OVA-induced asthma rats were significantly increased during animal experiments.Cell experiments showed that OVA could increase the expression of IL-2 5 in human bronchial epithelial cells in a dose-dependent manner,and OVA could upregulate the expression of transcription factor AP1.AP1 was found in the promoter region of IL-25 by site prediction.The AP1 inhibitor (T5224)significantly reduced the expression of IL-25 in OVA-induced human bronchial epithelial cells. Conclusion The molecular mechanism of IL-25 expression induced by OVA in asthma is related to the increase of transcription factor AP1 .
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Allergic airway inflammation is manifested as infiltration of CD4+ T cells and eosinophils in the airway,increased secretion of mucus,airway hyper-reactivity and airway remodeling.IL-25 is a member of the IL-17 family,which can promote and exacerbate Th2 cytokine-mediated airway inflammation after binding to its receptor IL-17RB.The increased IL-25 can induce the secretion of Th2 cytokines,including IL-4,IL-5 and IL-13,which may result in the local infiltration of eosinophils,airway hyperreactivity and therefore the injury of airway.As IL-25 plays an important role in allergic airway inflammation,the present paper would focus on the relationship between IL-25 and allergic airway inflammation.
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[ABSTRACT]OBJECTIVETo investigate the expression levels of IL-25 and IL-33 mRNA in the nasal mucosa of allergic rhinitis(AR) mice.METHODSBalb/c mice were used for establishing the animal model of allergic rhinitis with oval bumin sensitization as AR group, at the same time, the physiological saline as the control group. IL-25 and IL-33 mRNA in nasal mucosa of the two groups were detected by real-time quantitative PCR.RESULTSThe expression of IL-25 and IL-33 mRNA could be detected in both the control and AR group. The expression level of IL-25 and IL-33 mRNA in AR group were significantly higher than that in control group, the difference was statistically significant (P<0.05).CONCLUSIONIL-25 and IL-33 were involved in the development of allergic rhinitis. This result will be helpful for the further understanding of the pathogenesis of allergic rhinitis, and provide a theoretical basis for the treatment of allergic rhinitis.
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Objective To explore the effects of narrow-band ultraviolet B (NB-UVB)on the serum levels of thymic stromal lymphopoietin (TSLP)and interleukin-25 (IL-25), as well as on the expressions of TSLP receptor (TSLPR)and IL-25 receptor (IL-25R)mRNAs in peripheral blood mononuclear cells (PBMCs)from patients with atopic dermatitis(AD). Methods A total of 40 patients with AD and 30 healthy volunteers were enrolled in this study. All the patients were treated with NB-UVB at 0.3 - 2.5 J/cm2 thrice a week for 12 consecutive weeks. Venous blood samples were obtained from these patients before and after the treatment as well as from these healthy controls. Double-antibody sandwich enzyme-linked immunosorbent assay (ELISA)was performed to detect serum levels of TSLP and IL-25, and reverse transcription PCR(RT-PCR)to determine the mRNA expression levels of TSLPR and IL-25R in PBMCs from these subjects. The scoring atopic dermatitis (SCORAD)system developed by the European Task Force on Atopic Dermatitis was used to estimate the severity of AD, and visual analogue scale (VAS)to evaluate the degree of itch. Statistical analysis was carried out by the two-independent-sample t-test for intergroup comparisons and paired t-test for comparisons between pre- and post-treatment samples from these patients. Results After the treatment with NB-UVB, the total response rate reached 75%(30/40)in these patients, with a significant decrease in SCORAD score from 55.26 ± 10.88 before the treatment to 20.36 ± 5.12 after the treatment (t = 10.29, P 0.05). Conclusions TSLP and IL-25 may play important roles in the development of AD, and NB-UVB may treat AD by downregulating the expressions of them and their receptors.
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Objective To investigate the mechanism of therapeutic action of dexamethasone on asthmatic mice by detecting the levels of IL-25 and IFN-γ in bronchoalveolar lavage fluid (BALF). Methods Balb/c mice with SPF grade were randomly divided into normal control group, asthma group and dexamethasone group. Asthma group and dexamethasone group were sensitized and challenged with ovalbumin ( OVA) . Dexamethasone group was intraperitoneally injected with dexamethasone one hour before challenging. The mice were executed 24 hours after the last challenge, and the HE stained pathological sections of the right lung were made. Pathological sections of lung were observed. BALF in the left lung was also collected. The total white blood cell count and absolute eosinophile ( EOS) count were observed, and the percentage of EOS was calculated. The levels of IL-25 and IFN-γwere measured with ELISA, and correlation analyses were made. Results The counts of total white blood cell and EOS, and the percentage of EOS were significantly higher in the asthma group than in the normal control group and dexamethasone group (P<0. 05). No differences were found between the normal control group and dexamethasone group. The IL-25 level was higher in the asthma group than in the normal control group and dexamethasone group (P<0. 05), and its level in the dexamethasone group was also higher than that in the normal control group. The IFN-γlevel was lower in the asthma group than in the normal control group and dexamethasone group (P<0. 05), while there was no significant difference between the normal control group and dexamethasone group. IL-25 was negatively correlated with IFN-γin each group. Conclusion Part of the mechanisms of dexamethasone acting on asthma are related to its inhibition on the pulmonary inflammation and promotion on the expression of IFN-γ, and possible inhibition of IL-25 expression.
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Objective To detect the expression levels of interleukin (IL)-25 and IL-33 in peripheral blood of patients with chronic urticaria.Methods Ninety-three patients with chronic urticaria were included in this study along with 30 healthy individuals.All the patients were treated with loratadine for four weeks.Blood samples were collected from the healthy controls and patients before and after the four-week treatment.Enzyme-linked immunosorbent assay (ELISA) was performed to detect the serum levels of IL-25 and IL-33.The relationship between the expression levels of the two cytokines and urticaria severity was analyzed.Results The serum levels of IL-25 and IL-33 in the patients before treatment were significantly higher than those in the healthy controls (IL-25,139.86 ± 28.48 vs.114.41 ± 34.00 ng/L,P ＜ 0.01; IL-33,91.95 ± 21.88 vs.79.80 ± 30.72 ng/L,P ＜ 0.05),and positively correlated with the severity of urticaria (r =0.38,0.42,respectively,both P ＜ 0.01).After four weeks of treatment,clinical improvement was observed in 81.72％ of these patients with a significant decrease in the serum IL-25 level (116.48 ± 21.94 vs.139.86 ± 28.48 ng/L,P ＜ 0.01),but no obvious changes in the serum IL-33 level (90.88 ± 20.62 vs.91.95 ± 21.88 ng/L,P ＞ 0.05) compared with those before treatment.Conclusions The expressions of IL-25 and IL-33 are elevated in peripheral blood of patients with chronic urticaria,and positively correlated with the severity of urticaria.
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A total of 59 untreated asthmatics and 47 healthy control subjects were recruited from Qianfoshan Hospital of Shandong Province from May 2011 to April 2012.Compared with healthy control subjects,the levels of IL-25 in induced sputum and eosinophils,IgE,interleukin-4 (IL-4) and interleukin25 (IL-25) in serum samples of asthmatics were significantly higher while the level of interferon-gamma (IFN-γ) were much lower.However,after inhaled glucocorticoid treatment,the levels of eosinophils,IL-4 and IL-25 decreased and IFN-γ significantly increased,while the level of IgE showed no significant changes.It was also found the expression of IL-25 was markedly positively correlated with the levels of eosinophils and IL-4 in serum and markedly negatively correlated with the levels of IFN-γ and had no relatio.
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Objective To investigate the roles of interleukin(IL)-25,eosinophils in the occurrence of bronchial asthma.Methods Selected 30 cases of acute episode of asthma(asthma group),and ease a group of 23 cases of asthma treatment(remission group),20 cases of the normal control group.Using the method of gradient ultrasonic atomizing inhalation of Hyperosmotic saline collection of induced sputum specimens,by ELISA method for the determination IL-25 level in induced sputum,count of eosinophils,analysis of correlation between them.Results Group IL-25 in induced sputum of asthma and eosinophil levels[(313.12±75.64)ng/L vs(236.43±57.90)ng/L]were sig-nificandy higher than the control group[(0.386±0.267) × 109/L vs(0.005±0.002) × 109/L],and significantly higher than acute stage in remission stage[(268.63 + 40.19) ng/L,(0.120 + 0.016) × 109/L](P ＜ 0.05).Conclusion IL-25 has an important role in asthma development.It provides a new way of thinking for monitoring and treatment.
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Objective To explore the function and significance of interleukin(IL)-25 in the pathogenesis of inflammatory bowel disease (IBD) through testing its expression in the intestinal mucosal and serum of patients with IBD. Methods Intestinal or colonic mucosal biopsies of 12 patients with ulcerative colitis (UC), 16 patients with Crohn's disease (CD) and 10 healthy controls were collected. The expression of IL-25 at mRNA level was detected by real-time PCR and the situ expression of IL-25 in intestinal mucosa was analyzed with immunohistochemistry. At same time,serum of 20 UC patients, 24 CD patients and 20 controls was collected, and IL-25 concentration in the serum was determined by enzyme-linked immunosorbent assay (ELISA). Results Compared with healthy controls, the expression of IL-25 at mRNA level in inflamed mucosa of CD and UC patients was significantly decreased (P＜0.05), no statistic difference between UC and CD groups (P＞0.05).The immunohistochemistry results indicated that more IL-25 positive cells in normal lamina propria,the expression of IL-25 in mucosal epithelia cells was low, the expression of IL-25 protein in the intestinal or colonic mucosa of UC and CD patients significantly decreased ( P ＜ 0.05), no statistic difference between UC and CD groups (P＞0. 05). ELISA results showed that the level of IL-25 in the serum of UC and CD groups was significantly lower than healthy controls (P ＜ 0.05). Conclusion The expression of IL-25 in the intestinal mucosa and serum of IBD patients was significantly decreased,which suggested that IL-25 expression defects may closely related to the pathogenesis of IBD. IL-25 may be a new target for the IBD treatment.
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Many newly discovered interleukins have been implicated to play an important role in the pathogenesis of the allergic diseases, for example, human interleukin (IL)-17, a T-cell derived cytokine; interleukin (IL)-18, an interferon (IFN)-gamma-inducing cytokine; interleukin (IL)-23, produced by activated dendritic cells, and interleukin (IL)-25, a recently described T helper 2 (Th2) cell-derived cytokine. Understanding their characteristic and roles in diseases may help us to know better the mechanism of the allergic diseases and develop the strategy for treating the disease. [