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G protein-coupled receptors (GPCRs) represent the largest family of membrane proteins and are the target of approximately half of all therapeutic drugs. There are ～300 orphan GPCRs, which have great potential in drug development. G protein-coupled receptor 35 (GPR35), a rhodopsin-like orphan GPCR, is widely involved in immune regulation, gastrointestinal disorders, cardiovascular diseases, cancer, as well as other diseases, suggesting its great potential as a therapeutic target in a variety of diseases. However, the current research on GPR35 is insufficient, including the true endogenous ligand has not been confirmed, the molecular mechanism of its role in disease is not fully understood, and there is a lack of effective intervention strategies targeting GPR35. This article summarizes the deorphatization of GPR35, GPR35-related signaling pathways and their association with various diseases, in order to provide a reference for in-depth study of GPR35 in diseases and development of drugs targeting GPR35.
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Bombesin receptor subtype-3(BRS-3) is an orphan receptor in the bombesin receptor family. Its signal transduction mechanism and biological function have attracted much attention. Seeking the ligand for BRS-3 is of great significance for exploring its function. Considering the fact that the activation of BRS-3 receptor can induce the change in intracellular Ca~(2+) concentration, the fluo-rometric imaging plate reader(FLIPR) was utilized for ligand screening at the cellular level. Among more than 400 monomeric compounds isolated from Chinese herbs, yuanhunine from Corydalis Rhizoma and sophoraisoflavanone A and licoriphenone from Glycyrrhizae Radix et Rhizoma antagonized BRS-3 to varying degrees. It was confirmed in HEK293 cells expressing BRS-3 that yuanhunine, sophoraisoflavanone A, and licoriphenone inhibited the calcium current response after the activation of BRS-3 by [D-Phe~6,β-Ala~(11),Phe~(13),Nle~(14)]bombesin-(6-14) in a dose-dependent manner with the IC_(50) values being 8.58, 4.10, and 2.04 μmol·L~(-1), respectively. Further study indicated that yuanhunine and sophoraisoflavanone A exhibited good selectivity for BRS-3. In this study, it was found for the first time that monomers derived from Chinese herbs had antagonistic activity against orphan receptor BRS-3, which has provided a tool for further study of BRS-3 and also the potential lead compounds for new drug discovery. At the same time, it provides reference for the research and development of innovative drugs based on the active ingredients of Chinese herbs.
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Humans , Drugs, Chinese Herbal/chemistry , HEK293 Cells , Ligands , Receptors, BombesinABSTRACT
Objective:To explore the anti-inflammatory effect of pomegranate peel polyphenols on a rat auriclular model of acne and its mechanism of action.Methods:Totally, 36 specific-pathogen-free SD rats were randomly divided into 6 groups: blank group, model group, low-, medium- and high-dose pomegranate peel polyphenol groups and positive control group. In all groups except the blank group, 0.5 ml of 100% oleic acid was applied to the openings of bilateral auricular ducts once a day for 3 consecutive weeks, followed by subcutaneous injections of 50 μl of Propionibacterium acnes suspension at the oleic acid-applied sites once a day for 3 consecutive days, so as to establish a rat auriclular model of acne. After the model was confirmed to be successfully established by naked eyes, the low-, medium-, high-dose pomegranate peel polyphenol groups were topically treated with 0.5 mg of 1.4%, 2.8%, 5.6% (mass fraction) pomegranate peel polyphenol ointment respectively, the positive control group was topically treated with 0.5 mg of clindamycin hydrochloride gel, and the blank group and model group were topically treated with the same amount of distilled water. All the topical treatments were performed twice a day for 2 consecutive weeks. Twenty-four hours after the last topical treatment, abdominal aortic blood samples were collected, and enzyme-linked immunosorbent assay (ELISA) was conducted to detect the serum level of interleukin 17 (IL-17) in rats; rat auricular tissues were resected, hematoxylin-eosin (HE) staining was performed to observe histopathological changes of the skin tissues in each group, and immunohistochemical study to determine the expression of mammalian target of rapamycin (mTOR) , hypoxia-inducible factor-1α (HIF-1α) , and retinoic acid-related orphan receptor-γt (RORγt) in local tissues. Data meeting the assumptions of homogeneity of variances were analyzed by using one-way analysis of variance, and those that did not meet the assumptions of homogeneity of variances were analyzed by using Kruskal-Wallis H test; multiple comparisons were performed by using least significant difference- t test. Results:Compared with the model group, the pomegranate peel polyphenol groups and positive control group showed marked improvement in cysts, desquamation, crusts and epidermal keratinization, and reduced infiltration with inflammatory factors in the dermis at the modeling site. The serum level of IL-17 was significantly lower in the low-, medium- and high-dose pomegranate peel polyphenol groups (61.03 ± 5.99 ng/L, 55.35 ± 2.24 ng/L, 54.35 ± 4.29 ng/L, respectively) , positive control group (48.11 ± 4.07 ng/L) and blank group (42.10 ± 5.62 ng/L) than in the model group (70.24 ± 3.30 ng/L; t = 3.12, 5.34, 5.70, 8.29, 10.54, respectively, all P<0.05) . Immunohistochemical study revealed that the HIF-1α expression level was significantly lower in the low-, medium- and high-dose pomegranate peel polyphenol groups (0.29 ± 0.05, 0.29 ± 0.03, 0.33 ± 0.02, respectively) and positive control group (0.30 ± 0.01) than in the model group (0.41 ± 0.04; t = 4.89, 5.50, 3.62, 5.21, respectively, all P<0.05) ; the RORγt expression level was significantly lower in the low- and high-dose pomegranate peel polyphenol groups (0.28 ± 0.02, 0.31 ± 0.04, respectively) than in the model group (0.35 ± 0.02, t = 3.68, 2.18, respectively, both P<0.05) ; there was no significant difference in the mTOR expression level among these groups ( P = 0.119) . Conclusion:Pomegranate peel polyphenols could improve inflammatory reactions in the rat auriclular model of acne, which may be related to the down-regulation of HIF-1α/RORγt signaling pathway.
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Objective::To study the effect of warming and heat-clearing method (Wenyang Jiedu Huayu decoction) on the expressions of Forkhead box P3 (FoxP3), Retinoic acid-related orphan receptor gamma t (ROR-γt) in colon tissue of mice with acute-on-chronic liver failure (ACLF), in order to explore the possible regulatory mechanism on intestinal endotoxemia (IETM) in liver failure mice. Method::The 130 SD rats were randomly divided into normal group (10 rats) and model group (120 rats). The ACLF mice model was established through the subcutaneous injection with bovine serum albumin and the intraperitoneal injection with D-galactosamine(D-Gal) and lipopolysaccharide (LPS). The model mice were randomly divided into model group, heat-clearing group (Yinchenhao decoction, 6.68 g·kg-1), warming group (Yinchen Zhufu decoction, 7.09 g·kg-1) and warming and heat-clearing group (Wenyang Jiedu Huayu decoction, 19.53 g·kg-1). The normal group and the model group were given distilled water by gastric lavage, while the other groups were given equal volume of corresponding Chinese herbal medicines for a week. The value of each index at 1, 12 and 24 h was measured. The ratio of Treg/Th17 cell in peripheral blood were detected and calculated by flow cytometry. Real-time fluorescence quantitative PCR (Real-time PCR) was used to detect the expressions of FoxP3 and ROR-γt in colon tissues of mice at different time points. In situ hybridization and immunohistochemistry were used to observe the expressions of FoxP3 and ROR-γt genes and proteins. Result::Compared with normal group, the ratio of Treg/Th17 in the model group decreased significantly at each time point (P<0.01). Compared with the model group, the Treg/Th17 ratio increased only in the warming and heat-clearing method group (P<0.05). Compared with normal group, the expression of ROR-γt in the model group was significantly higher (P<0.01), and the expression of ROR-γt in the model group was higher than FoxP3.Compared with the model group, the expressions of FoxP3 and ROR-γt mRNA in the heat-clearing group and the warming group decreased at each time point (P<0.05), and the expressions of FoxP3 and ROR-γt in the warming and heat-clearing method group decreased significantly (P<0.01). The expressions of FoxP3 and ROR-γt mRNA in warming and heat-clearing group decreased compared with those in the warming group and heat-clearing group (P<0.05). Conclusion::The mechanism of the warming and heat-clearing method on IETM in liver failure may be related to the regulation of FoxP3 and ROR-γt expressions.
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OBJECTIVE: To observe the effect of acupoint injection on expression of fork head/winged helix protein 3 (Foxp3), retinoic acid-related orphan receptor γt (RORγt) in nasal mucosa and serum interleukin-17 (IL-17) level in allergic rhinitis (AR) rats, so as to explore its mechanism underlying improvement of AR in terms of balancing Th17/Treg. METHODS: Thirty-two SD rats (half male and half female) were randomized into normal control, AR model, acupoint injection and non-acupoint injection groups (n＝8 in each group). The AR model was established by ovalbumin sensitization. In the acupoint injection group, "Yintang" (EX-HN3) and bilateral "Yingxiang"(LI20) were selected for injection of mixture solution of dexamethasone (DEX) and transfer factor and lidocaine (0.1 mL/acupoint), once every 3 days for a total of 4 times. The non-acupoints, located at the mid-point between the "Houhai" (GV1) and "Huantiao"(GB30) on the bilateral hips and the sites 5 cm inferior to the axillary were injected with the same dose of mixture solution as that in the acupoint injection. The AR severity was assessed by cumulative quantification scoring methods (including the numbers of nose-catching and sneezes, and the amount of nasal secretions in 30 min). The expressions of Foxp3 and RORγt in the nasal mucosa were detected by immunohistochemistry. The serum IL-17 content was detected by enzyme linked immunosorbent assay (ELISA)．. RESULTS: The AR symptom score and serum IL-17 content were significantly higher in the AR model group than those in the normal control group (P0.05). The percentage of the Foxp3 positive cells and the ratio of Foxp3/RORγt were negatively correlated with the AR symptom score(P<0.05), the expression of RORγt and the content of IL-17 were positively correlated with the symptom score (P<0.05)．. CONCLUSION: Acupoint injection is able to improve symptoms of RA rats, which may be related with its function in up-regulating the level of nasal mucosal Foxp3 and suppressing the levels of nasal RORγt and serum IL-17 to correct the imbalance of Th17/Treg.
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Objective: To observe the effects of RuanJianXiaoYing Granule on the expressions of specific transcription factors and cytokines of Treg and Th17 in the Hashimoto thyroiditis (HT) rats with liver depression and spleen deficiency, and to investigate the therapeutic effect of RuanJianXiaoYing Granule on HT and its immunological mechanism. Methods: A total of 48 SD rats were randomly divided into normal group (12 rats) and modeling group (36 rats). The HT model was established by subcutaneous injection of excessive iodine drinking water and thyroglobulin, and then combined with chronic restraint stress, excessive fatigue and dietary disorders to prepare the rat models with liver depression and spleen deficiency. After modeling, the rats were randomly divided into model group (n=12), Tripterygium wilfordii group (n=12), and RuanJianXiaoYing group (n=12), and the rats were treated for 8 weeks. In addition to the dead rats and unqualified specimens during the experiment, the test results of 10 rats in each group were retained. The general situation of the rats in various groups was observed; the abdominal aortic blood and thyroid gland tissue of the rats in various groups were collected after the last administration; the levels of thyroglobulin antibody (TGAb), thyroid peroxidase antibody (TPOAb), free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin-releasing hormone (TRH) and thyrotropin (TSH) in serum and the levels of IL-17, IL-23 and IL-10 were detected by ELISA method; the pathomorphology of thyroid gland tissue of the rats in various groups were detected by HE staining; the expression levels of Foxp3 and RORyt proteins in thyroid gland tissue of the rats in various groups were detected by Western blotting method. Results: Compared with normal group, the levels of serum TGAb and TPOAb of the rats in model group, Tripterygium wilfordii group and RuanJianXiaoYing - group were increased (P0. 05); the level of serum IL-10 was increased (P<0. 05), and the levels of serum IL-17 and IL-23 were decreased (P<0. 05). The follicular cavity of thyroid gland in normal group had regular morphology, complete structure and no lymphocyte infiltration. In model group, the follicular cavity of thyroid gland was enlarged, the follicular structure was destroyed, and a large number of lymphocyte infiltration was observed in and around the follicular cavity. In Tripterygium wilfordii group, the follicular cavity of thyroid gland was enlarged, part of the follicular structure was destroyed, and there was a small amount of lymphocyte infiltration in and around the follicular cavity, which was less than that in model group. The morphological changes of thyroid gland in RuanJianXiaoYing group were similar to those in Tripterygium wilfordii group Conclusion: RuanJianXiaoYing Granule has the therapeutic effect in the HT rats with liver depression and spleen deficiency by regulating the expressions of the specific transcription factors Foxp3 and RORγt protein and related cytokines of Treg and Th17.
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This study was to investigate the effect of RORα activator SR1078 on ovarian cancer cells and its molecular mechanism in vitro. The survival rate of HeyA8 and Hey cells was detected by MTS assay; the apoptosis and cells cycle distribution after SR1078 treatment and the effect of p53 siRNA or PFT-α and PFT-β of p53 inhibitors on SR1078-induced apoptosis of HeyA8 or Hey cells were analyzed by flow cytometry. Western blot was used to detect the effect of SR1078 and p53 siRNA on the expression of p53 protein and the effect of p53 inhibitors alone or in combination with SR1078 on the expression of p53, p-p53 and its downstream pro-apoptotic protein Noxa. The results showed that SR1078 significantly reduced the cell viability and induced apoptosis in HeyA8 and Hey cells. In addition, SR1078 up-regulated the protein expression of p53 and Noxa, and p53 suppression led to significant inhibition of SR1078-induced apoptosis and the expression of Noxa in ovarian cancer cells. In summary, SR1078 induced apoptosis of ovarian cancer cells by activation of p53 signaling pathway.
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Objective: To investigate the effect of interferencing receptor tyrosine kinase-like orphan receptor 1 (ROR1) gene expression on epithelialmesenchymal transition (EMT) of osteosarcoma MG-63 cells. Methods: The specific siRNA targeting ROR1 gene (ROR1-siRNA) was transfected into osteosarcoma MG-63 cells with the relative high expression of ROR1 protein, then the down-regulation of ROR1 expression was confirmed by Western blotting. The migration and invasion abilities of MG-63 cells were examined by scratch wound healing assay and Transwell chamber assay. The morphological changes of MG-63 cells were observed under an inverted optical microscope. Finally, the expressions of EMT-associated E-cadherin and vimentin, and tumor metastasis-related zinc finger E-box binding homeobox protein 1 (ZEB1), matrix metalloproteinase 2 (MMP-2) and MMP-9 proteins in MG-63 cells were detected by Western blotting and immunofluoresence staining, respectively. Results: ROR1-siRNA transfection significantly inhibited the expression of ROR1 in MG-63 cells (P < 0.05). After down-regulating ROR1 gene expression by ROR1-siRNA transfection, the migration and invasion abilities of MG-63 cells were significantly reduced (both P < 0.05), the morphology of MG-63 cells conversed from mesenchymal phenotype to epithelial phenotype, and the expression level of E-cadherin was significantly up-regulated (P < 0.05), while the expression level of vimentin was significantly down-regulated (P < 0.05). Furthermore, the expressions of ZEB1, MMP-2 and MMP-9 in MG-63 cells transfected with ROR1-siRNA were decreased as compared with those in the untransfected group (all P < 0.05). Conclusion: RNA interference of ROR1 gene expression can reduce the migration and invasion abilities of osteosarcoma MG-63 cells through inhibiting the occurrence of EMT.
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OBJECTIVE: Recent studies have reported associations of retinoid-related orphan receptor alpha (RORA) gene single nucleotide polymorphisms (SNPs) with depression and anxiety disorders. Based on these, we attempt to test whether RORA polymorphism is associated with anxiety sensitivity (AS), the intermediate phenotype of depression and anxiety disorders. Considering gene-environment interactions and sex differences in AS, childhood maltreatment (CM) and sex were considered as confounders. METHODS: Two-hundred and five healthy young Korean adults (female: 98, male: 107; age, 23.0±3.2 years) completed genotyping for the RORA SNP rs11071547, as well as measures for AS and CM. Generalized linear models were used to examine the main and interaction effects of RORA genotype, CM, and sex in determining AS. RESULTS: The main effect of RORA polymorphisms was not found (p=0.760) whereas the main effect of CM and interaction effects among sex, genotype, and maltreatment were significant on AS. In separate analyses by sex, the interaction effect between RORA genotype and maltreatment was significant only in males (p < 0.001). In females, the main effects of genotype and CM were significant (both were p < 0.001), in which both a history of CM and C genotype tended to be associated with higher AS. CONCLUSION: The association between RORA polymorphism and AS might differ by sex. The interaction between RORA polymorphism and CM was significant only in males whereas RORA genotype and CM independently associated with AS in females. Further studies are encouraged to confirm the relationship between RORA polymorphism and AS.
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Adult , Child , Female , Humans , Male , Young Adult , Anxiety Disorders , Anxiety , Child, Orphaned , Depression , Gene-Environment Interaction , Genotype , Linear Models , Phenotype , Polymorphism, Single Nucleotide , Sex CharacteristicsABSTRACT
E2A is involved in promoting forkhead box P3 (FOXP3) and retinoid-related orphan receptor gamma t (RORγt) gene transcription,which are pivotal transcription factors of T regulatory cells and Thl7 cells,respectively.Little is known about the involvement of E2A in pregnancy process.This study aimed to investigate the expression of E2A,cytotoxic T-lymphocyte-associated protein 4 (CTLA-4),and Foxp3 in luteal phase endometrium of women suffering recurrent miscarriage (RM) (n=21) and control group (n=11) by immunohistochemistry,with the Vectra(R) automated quantitative pathology imaging system for analysis.The percentage of E2A+ cells and CTLA-4+ cells was significantly higher in the endometrium of women with RM than in the controls.There was positive correlation between E2A and CTLA-4 (r=0.523,P=0.002),E2A and FOXP3 (r=0.380,P=0.032),and FOXP3 and CTLA-4 (r=0.625,P=0.000) in the mid-secretory phase of endometrium for all subjects.It was concluded that the abnormal expression of endometrial E2A existed in mid-secretory endometrium of women with RM,and there was a positive correlation between E2A and FOXP3,and E2A and CTLA-4,suggesting the possible regulation role of E2A involved in regulating endometrium receptivity.
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<p><b>OBJECTIVE</b>To observe the expression of wingless-type MMTV integration site family, member 5A (Wnt5A)/receptor tyrosine kinase-like orphan receptor 2 (Ror2) signal in the dental follicle cells during the normal eruption of the teeth as well as to explore the relationship between the expression of dental follicle cells and the formation of mature osteoclasts and eruption of the teeth.</p><p><b>METHODS</b>The mandibulars of 1-13 d old SD rats were separated to observe the growth and develop-ment of the teeth and alveolar bone through hematoxylin-eosin(HE) staining. Ror2 and Wnt5A expressions in rat dental follicle were also observed through immunohistochemistry. Dental follicle cells from the lower first intact molar germs of 5-6-day old SD rats were separated and cultured.</p><p><b>RESULTS</b>On the second day after birth, the dental follicle began to differentiate into periodontal tissues, but no obvious changes were observed in the alveolar bone one to three days after birth. On the fourth day, the number of osteoclasts increased significantly. The results of immunohistochemistry showed that Wnt5A was not significantly expressed in rat dental follicle tissues before the fourth day, but positive expression was expressed in the next day and continued to express to thirteenth days. Ror2 was expressed in the rat dental follicle at postnatal days 1-3, but weak expression was found in days 4-13.</p><p><b>CONCLUSIONS</b>Wnt5A and Ror2 expressions in the process of tooth eruption have specific time distributions, suggesting that these expressions may participate in the regulation of the eruption of the teeth.</p>
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Animals , Rats , Dental Sac , Molar , Osteoclasts , Periodontium , Rats, Sprague-Dawley , Receptor Tyrosine Kinase-like Orphan Receptors , Tooth Eruption , Wnt Proteins , Wnt-5a ProteinABSTRACT
Objective To explore effect of grape seed proanthocyanidin extract (GSPE)on airway inflammation and hyperresponsiveness of ovalbumin-induced murine asthma model and the associated regulatory effect on Treg/Th17 imbalance.Methods A total of 40 mice were randomly assigned to four experimental groups:control,asthma model,low dose GSPE (40 mg/kg),and high dose GSPE (80 mg/kg).Acute asthma model was established with OVA;airway responsiveness of mice in each group was measured with a noninvasive pulmonary function instrument;lung inflammation changes were observed by pathological HE staining;Treg/Th17 cytokines levels in bronchoalveolar lavage fluid were evaluated by ELISA;the expressions of forkhead/winged helix transcription factor(Foxp3) mRNA and retinoid-related orphan receptor gammat (RORγt) mRNA in lung tissue of each group were gained by Real-time PCR method.Results GSPE inhibited ovalbumin-induced increases in airway responsiveness(P ＜ 0.05).Histological studies demonstrated that GSPE substantially inhibited OVA-induced airway inflammation in lung tissue.GSPE decreased IL-17A levels and increased IL-10 levels in bronchoalveolar lavage fluid (P ＜ 0.05).In the asthma model group,RORγt mRNA expression in lung tissue was significantly higher than that in the control group(P ＜ 0.05)and Foxp3 mRNA expression was significantly lower than that in the control group (P ＜ 0.05).In the GSPE group,RORγt mRNA expression was lower than that in asthma model group (P ＜ 0.05),however the Foxp3 mRNA expression was higher than that in asthma model group(P ＜ 0.05).Conclusion GSPE could alleviate airway hyperresponsiveness and airway inflammation of in asthmatic mice.It can modify the asthmatic mice Treg/Th17 imbalance by decreasing IL-17A and increasing IL-10 concentration at the level of cytokines;and also by increasing Foxp3 mRNA expression and inhibiting the expression of RORγt mRNA at the transcriptional level,which provide a new way for treatment of bronchial asthma.
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Interleukin-33 is regarded as the orphan receptor ST2 that belongs to the cytokine family of interleukin-1 in 2005. IL-33 is found to play a potentially pathogenic roles in the autoimmune disease, allergic disease, vascular disease, inflammatory disease and it might be a useful sera marker for the diagnosis and prognosis in related diseases. Here we make a review on the relationship between IL-33 and autoimmune disease in recent years.
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Objective To observe the changes in forkhead/winged helix transcription factor p3(Foxp3), regulatory T cells(Treg),retinoid-related orphan receptor gamma(RORγt)in rat model of chronic obstructive pulmonary disease(COPD). Methods Twenty Sprague-Dawley(SD)rats were randomly divided into normal control group and COPD model group,with 10 rats in each group. The COPD model was reproduced by smoke inhalation and tracheal instillation of lipopolysaccharide(LPS),and no such treatment was conducted in normal control group. Twenty-eight days after the model reproduction,the pulmonary function was determined,the pathological changes of lung tissue were observed with haematoxylin-eosin(HE)staining,interleukins(IL-6,IL-10)in serum were detected by enzyme-linked immunosorbent assay(ELISA),CD4+CD25+Foxp3+Treg of peripheral blood was determined by flow cytometry,and the expressions of Foxp3,RORγt,IL-17 protein in lung tissue were assayed by Western Blot. Results Under light microscope,significal interstitial infiltration of inflammatory cells was found in alveoli and interstitial tissue of the lung,and destruction of alveolar tissue,alveolar wall thinning,and even rupture to fuse into bullae,and bleeding into alveoli in different degress could be observed. Compared with the normal control group,forced vital capacity(FVC),forced expiratory volume in 0.3 second(FEV0.3),FEV0.3/FVC,peak expiratory flow(PEF)in model group were significantly decreased〔FVC(mL):8.04±2.03 vs. 9.97±2.14,FEV0.3(mL):6.16±2.23 vs. 8.84±2.12,FEV0.3/FVC:0.70±0.09 vs. 0.85±0.11,PEF(mL/s):33.56±4.76 vs. 40.14±5.64, P<0.05 or P<0.01〕. Serum IL-6 was obviously increased(ng/L:93.17±20.96 vs. 76.28±13.24,P<0.05), IL-10 was significantly decreased(ng/L:78.62±15.17 vs. 104.34±19.46,P<0.01),and CD4+CD25+FoxP3+Treg was significantly diminished〔(2.75±0.83)% vs.(4.16±1.14)%,P<0.01〕in model group compared with those in the normal control group. The expression of Foxp3 protein in lung tissue in model group was significantly down-regulated compared with that in the normal control group(gray scale:0.38±0.15 vs. 0.63±0.11,P<0.01), and RORγt and IL-17 protein expressions were significantly up-regulated〔RORγt(gray scale):0.96±0.23 vs. 0.47±0.11,IL-17(gray scale):1.02±0.24 vs. 0.34±0.08,both P<0.01〕. Correlation analysis showed that FEV0.3 was positively correlated with Foxp3(r=0.585,P<0.05),and FEV0.3/FVC was negatively correlated with IL-6 and RORγt(r=-0.655,r=-0.607,both P<0.05). PEF was positively correlated with Treg(r=0.573, P<0.05),and negatively correlated with IL-17(r=-0.198,P<0.05). IL-6 was negatively correlated with Foxp3(r=-0.603,P<0.05),and positively correlated with RORγt(r=0.588,P<0.05). IL-10 was positively correlated with Treg(r=0.573,P<0.05). Treg was positively correlated with Foxp3(r=0.607,P<0.05), and negatively correlated with IL-17(r=-0.569,P<0.05). Foxp3 was negatively correlated with RORγt(r=-0.591, P<0.05). RORγt was positively correlated with IL-17(r=0.578,P<0.05). Conclusion There is a relationship among decreased pulmonary function,inflammation and imbalance of Foxp3/Treg and RORγt/Th17 in COPD.
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BACKGROUND: Th2 cells are crucially important in allergic disease and the possible involvement of Treg and Th17 cells has not been clearly identified. OBJECTIVE: To identify the mRNA expression of T cell transcription factors in nasal mucosa in patients with allergic rhinitis (AR) and to reveal their correlations with clinical features. METHODS: Eighteen patients with AR and 12 controls with turbinate hypertrophy were included. mRNA expression of the following transcriptional factors in nasal mucosa were measured by quantitative polymerase chain reaction; T-bet (Th1), GATA3 (Th2), retinoic acid-related orphan receptor C (RORC; Th17), and forkhead box P3 (Foxp3; Treg). mRNA expression was compared among groups and correlation between mRNA expression level and clinical features (rhinitis symptoms, eosinophil count, and IgE) were also investigated. RESULTS: GATA3 and RORC were significantly increased and Foxp3 was significantly decreased in the AR group. Moderate-to-severe AR group also had increased expression of GATA3 and RORC than mild AR group, suggesting severity of AR influence expression of transcription factors. Correlation analysis showed that none of these transcription factors were associated with severity of clinical symptoms, eosinophil counts and skin prick test severity and that IgE level was significantly correlated with expression level of GATA3 and RORC, suggesting an association of IgE production with Th2 and Th17 cells. CONCLUSION: Increased mRNA expression of GATA3 (Th2), increased expression of RORC and decreased expression of Foxp3 may be important in pathogenesis of AR. GATA3 and RORC may be closed related with IgE level.
Subject(s)
Child , Humans , Child, Orphaned , Eosinophils , Hypertrophy , Immunoglobulin E , Nasal Mucosa , Polymerase Chain Reaction , Rhinitis, Allergic , RNA, Messenger , Skin , Th17 Cells , Th2 Cells , Transcription Factors , TurbinatesABSTRACT
Objective Single nucleotide polymorphisms(SNPs) in receptor tyrosine kinaselike orphan receptor 2 (ROR2) gene were analyzed and compared between Han Chinese in Beijing(CHB) and Japanese in Tokyo(JPT) using the HapMap data,to provide basis for SNP determination.ROR2 gene related etiologic studies were conducted in the above mentioned two populations.Methods Monotonic and un-monotonic SNPs of ROR2 gene were distinguished by Haploviewprogram.Minor allele frequency (MAF),haplotype blocks and haplotype frequencies were analyzed ineligible SNPs and tag SNPs respectively with genotyping call rate ＞80％,MAF＞1％,H-Wequilibrium (P＞0.01) and no gender difference (P＞0.05).Tag SNPs were determined under thecriteria of r2≥0.8 or logarithm of the odd score (LOD) ≥3 for pairwise eligible SNPs in CHB and JPT.Common tag SNPs for CHB and JPT were directly reported by Haploview program or being identified from those which were higly related to tag SNPs reported by haploview program under SPSS 13.0 software.Results A total of 404 common SNPs were provided for both CHB and JPT samples by HapMap,where 101 common monotonic SNPs between CHB and JPT had the common minor alleles.The common SNPs between CHB and JPT were 257.In the 257 common eligible SNPs,224 (87.2％) had common minor alleles.Among the 18 and 27 haplotype blocks identified in 257common eligible SNPs between CHB and JPT,except for 2 independent haplotype blocks identified only in JPT.Other haplotype blocks between CHB and JPT were overlapped partly or completely.A number of 50 common tag SNPs between CHB and JPT were determined and the proportions in CHB and JPT were 64.9％ and 70.4％ respectively.Conclusion Analysis of HapMap data provided an opportunity to avoid monotonic SNPs that had been included in ROR2 gene related etiologic studies.SNPs in ROR2 gene had common features in alleles,MAF,haplotype blocks and haplotype frequencies between CHB and JPT populations,which were consistent with the geographic and ethnic origins of the two populations.