ABSTRACT
Background; Immunological dysfunction plays a key role in the pathogenesis of inflammatory bowel disease (I B D). Notopterol is the main ingredient of the traditional Chinese herb medicine Notopterygium ineisum Ting ex H. T. Chang and has anti-inflammatory effect. Aims; To explore the effect of notopterol on dextran sulfate sodium (DSS)-induced colitis in mice. Methods; C57BL/6 mice were randomly divided into normal group, negative control group, model group and notopterol group. Mice in model group and notopterol group were treated with 2% DSS to induce colitis. Mice in negative control group and notopterol group were injected intraperitoneally with notopterol 40 mg/kg, and mice in normal group and model group were injected intraperitoneally with 0. 9% NaCl solution. Mice were sacrificed 10 days later, and disease activity index (DAI) score, colon length and histopathologieal score were determined. The levels of TNF-α, IL-1β, IL-6, IL-17A were assessed by ELISA. The mRNA expressions of IL-17A, RORγt were detected by quantitative PCR. Results; Compared with the normal group, DAI score, histopathologieal score, levels of TNF-α, IL-1β, IL-6, IL-17A, mRNA expressions of IL-17A and RORγt in model group were significantly increased (P < 0. 0 1), and colon length were significantly shortened (P < 0. 0 1). Compared with the model group, notopterol significantly reduced DAI score and histopathologieal score (P<0.01), downregulated levels of TNF-α, IL-1β, IL-6, IL-17A (P<0.01), inhibited the mRNA expressions of IL-17A, ROR-γt (P < 0. 0 1), and greatly recovered colon length (P < 0. 0 1). Conclusions; Notopterol has protective effects on DSS-induced colitis in mice. The mechanism may be related to reducing the secretion of pro-inflammatory cytokines and inhibiting the function and differentiation of Thl7 cells.
ABSTRACT
Aim: To explore the role of paeoniflorin-6'- O-benzenesulfonate (CP-25) in MRL/lpr mice and the regulating action on Thl7 cell differentiation. Methods MRL/lpr mice were randomly assigned to five groups as follows; model group, CP-25 (20, 40, 80 mg · kg
ABSTRACT
Aim To observe the anli-granuloma of resveratrol in mice with schistosomiasis japonica and its effect on Thl7 and Treg responses. Methods Forty- five mice infected with S. japonieum cercariae for three weeks were randomly divided into three groups named as infected group ( A ) , resveratrol group ( H ) and praziquantel group ( C). Fifteen normal mice were taken as normal control group (D). At the 9th week post-infection, the granuloma of the liver tissues was observed using HE staining, and the number of neutrophils was calculated. IL-17A, CXCL1, CXCL2, Foxp3 levels in liver tissues were delected by RT-PCR. Thl 7 and Treg responses in spleen were determined by FCM respectively. Splenocytes from healthy mice were stimulated by PBS and SEA respectively. After SEA stimulation, resveratrol and praziquantel were added respectively, and Thl7 and Treg responses were detec ted by FCM. Results Compared to group A, the granuloma was alleviated ( P < 0. 01 ) , the number of neutrophils in single granuloma was reduced ( P < 0.01), Thl7 response significantly decreased (P < 0. 05) and Treg response increased markedly in group B ( P <0.05). The hepatic expression of IL-17A, CXCL1 , CXCL2 levels in group B was lower than that of group A (P< 0.05), and Foxp3 level in group B were higher than in group A(P <0. 01 ). In vitro, resveratrol inhibited the differentiation of Thl7 cells (P < 0. 05 ) and enhanced that of Treg cells after SEA treatment ( P < 0. 05 ). Conclusion Resveratrol inhibits the heptic granulomatous response through down-rcgu- lating Thl7 res()onse and up-regulating Treg response in mice with schistosomiasis.
ABSTRACT
Aim To explore the effect of ZishenT-ongluo formula (ZTF) on the differentiation and the balance of Thl7/Treg cells in collagen-induced arthritis ( CIA) and its mechanisms. Methods DBA/1 mice were used to induce the arthritis model through injecting collagen II , and they were randomly divided into the model group and ZTF group (8. 4 g • kg-1) 21 days later. Another DBA/1 mice were used as control. General conditions and joint swelling were observed. After four weeks of administration, the histopathologic changes of ankle tissues, the levels of IL-10 and IL-17 in plasma, the ratio of Thl7 and Treg cells in peripheral blood and spleen, and the expression of IL-10 and IL-17 mRNA in CD4+ T cells were measured. Results CIA mice showed significant joint swelling. The levels of IL-17 in plasma of CIA mice significantly increased and the levels of IL-10 significantly decreased. The proportion of Thl7 cells in blood and spleen, and the expression of IL-17 mRNA in CD4+ T cells increased significantly, while the proportion of Treg cells and the expression of IL-10 mRNA decreased significantly in CIA mice. After treating with ZTF, the joint swelling and arthritis scores were obviously reduced, the levels of IL-17 in plasma decreased and the levels of IL-10 increased. Meanwhile, the proportion of Thl7 cells in blood and spleen, and the expression of IL-17 mRNA in CD4+ T cells decreased, while the proportion of Treg cells and the expression of IL-10 mRNA increased. Conclusions Thl7/Treg cell imbalance exists in CIA mice. ZTF could regulate the ratio of Thl7 and Treg cells, resume the Thl7/Treg balance, and then regulate the release of related cytokines. That may be one of the mechanisms of ZTF in treating rheumatoid arthritis.
ABSTRACT
Objective: To investigate the inhibitory effects of astragalus polysaccharides (A P S) with different molecular weights on the pulmonary inflammaton in the asthmatic mice, and to elucidate their mechanisms. Methods: A total of 30 female BALB/c mice were selected. They were randomly divided into normal control group, asthma model group (model group), low molecular weight APS (APS-low) group, midde molecular wieght APS (APS-middle) and high molecular weight APS (APS-high) group, with 6 mice in each group. The mouse models of asthma in model group and APS groups were established by injecting and inhaling ovalbumin (OVA). The mice in APS-low, APS-middle and APS- high groups were separately given 0. 1 mL of 4 500, 15 000, 30 000 molecular weight APS for intrapeitoneal injecton before inhaled OVA The mice in normal control group were treated with the same amount of normal saline instead of OVA injected and inhalled. The behavioral changes of the mice were observed during the atomization with OVA, and the total number of WBC and the counts of inflammatory cells in the bronchoalveolar lavage fluid (BALF) were observed with light microscope; the pathological changes of lung tissue was observed by HE staining. Cytometric Bead Array (CBA) method was used to detect the levels of IL-4 and IFN -y in the serum as well as BALF. The spleen CD4 T cells were extracted and cultured, and the ratios of T h l, Th2, Thl7 and Treg cells were detected by flow cytometry. CBA method was used to detect the levels of IL-4, IFN-y, IL-17, and IL-10 in the culture supernatant. Results: Compared with normal control group, the mice in model group showed asthma-like symptoms such as sneezing, snouting nose and shortness of breath, inflammatory infiltration of lung tissue, airway mucosal edema, smooth muscle thickening; the IL-4 levels in serum and BALF were increased (P < 0 . 05), and the IFN-y levels in serum and BALF were significantly decreased (P < 0 . 05); IL-4 and IL-17 levels in cell culture supernatant were significantly increased (P < 0 . 05), and the IFN-y and IL-10 levels were significantly decreased (P < 0 . 05); the ratios of Th2 and Thl7 cells were significantly increased (P < 0 . 05), and the ratios of T h l and Treg cells were significantly decreased (P < 0 . 05). Compared with model group, the asthmatic symptoms of the mice in APS groups, for example, scratching nose and mouth, shortness of breath, and irritability, were relieved to varying degrees; the inflammatory cell infiltration and wall thickening were significantly improved; the levels of IL-4 in serum and BALF were significantly reduced (P < 0 . 05), and the IFN -y levels were increased (P < 0 . 05); the levels of IL-4 and IL-17 in the culture supernatant were significantly reduced (P < 0 . 05) and the levels of IFN-y and IL-10 were increased (P < 0 . 05); the ratios of Th2 and Thl7 cells were significantly decreased (P < 0 . 05), and the ratos of T h l and Treg cells were increased (P < 0 . 05). Compared between three APS groups, the asthmatic symptoms and lung tissue inflammatory infiltration were lightened obviously in APS-low group, the IL-4 levels and the ratios of Th2 and Thl7 cells in serum and BALF were significantly decreased (P < 0. 05), and the IFN-y levels in serum and BALF and the ratios of Th2 and Thl7 cells were significantly increased (P < 0 . 05). Conclusion: APS can significantly improve the situaton of airway inflammaton infiltraton and the symptoms of the asthmatic mice. APS plays a therapeutic role for asthma by regulating the Th 1 / Th 2 and Th l7 / Treg cell balance, decreasing the levels of IL-4 and IL-17 and increasing the levels of IFN -y and IL-10 level; the low molecular weight APS shows an obvious effect.
ABSTRACT
Bronchiolitis is a common lower respiratory infectious disease in children under two years old.The main pathogen of bronchiolitis is respiratory syncytial virus.Bronchiolitis is also associated with asth-ma.It is still unknown for us about the pathogenesis of bronchiolitis.In recent years,we were found find that the T helper l7 cell(Thl7)and regulatory T cell(Treg)play an important role in bronchiolitis.We review the role of Thl7/Treg imbalances in the pathogenesis of bronchiolitis in this paper.
ABSTRACT
Objective To investigate the expression characteristics of T lymphocyte subsets in peripheral blood of patients with newly diagnosed multiple myeloma(MM),as well as the equilibrium relationship between the ratio of helper T cells 17(Thl7)and CD4+CD25+Foxp3+regulatory T cells(Treg cells),and analyze their clinical significance in the pathogenesis of MM.Methods The proportion of CD3+,CD3+CD4+,CD3+CD8+cells,Th17 cells,Treg cells in peripheral blood and the ratios of CD3+CD4+/CD3+CD8+、Th17/Treg were analyzed between the 30 patients with MM in newly diagnosed and 20 healthy volunteers(control group),then analysis the differences between MM patients and control group.In 30 cases of newly diagnosed MM patients(patient group)and 20 healthy volunteers(control group),total T cells in peripheral blood(CD3+),auxiliary T cells /induced T cells(CD3+CD4+),the inhibitory T cell /cytotoxic T cells(CD3+CD8+),the ratio of(CD3+CD4)/(CD3+CD8+),the percentages of Th17 cells and Treg cell and the ratio of Thl7 and Treg were detected,and the differences between MM patients and control group were compared.Results The ratio of inhibition/cytotoxic T cells(CD3+CD8+)in the patient group was higher than that in the control group(P<0.05).(CD3+CD4+)/(CD3+CD8+)ratio in the patient group was lower than that in the control group(P<0.05);in the patient group,the ratio of Th17 cells in peripheral blood of patients was(5.9 ± 1.9)%,which was increased compared with the control group(4.0 ± 0.9)%(P<0.05);the ratio of Treg cells in the patient group was(1.2 ± 0.3)%,which was decreased com-pared with the control group(2.1 ± 0.4%)(P< 0.05);and the ratio of Th17/Treg cells was significantly higher in the patient group,and the difference was statistically significant(P<0.05).Conclusion Peripheral blood T cell subsets disorder exists in pa-tients with MM,Thl7/Treg cell imbalance caused by the increase of Thl7 cell ratio and the decrease of the ratio of Treg cells,and the imbalance of immune system may play a role in the occurrence and development of MM,and has some guiding value for the prognosis.
ABSTRACT
Objective To investigate the changes of Treg cells,Th17 cells and related cytokines in pe?ripheral blood of patients with severe hand?foot?mouth disease( HFMD) in the initial stage of infection caused by Enterovirus 71 virus. Methods Thirty?five cases of severe HFMD children in the Fifth Hospital of Shijiazhuang from May 2013 to December 2013 were selected as the research subjects,including 27 cases of severe formed group and 8 cases of danger severe formed group. The frequencies of Th17 cells ( CD3+CD8?IL?17+) and Treg cells( CD4+CD25+Foxp3+) in peripheral blood were detected by flow cytometry in patients with severe HFMD and 31 healthy children(control group). Moreover the serum levels of interleukin 6(IL?6),interleukin 17(IL?17) ,interleukin 10( IL?10) ,interleukin 23( IL?23) ,and human transforming growth factorβ1 ( TGF?β1) were measured by ELISA. Results As compared with those in control group,the frequencies of Treg cells,ratio of Treg/Th17,serum levels of TGF?β1, IL?10 in severe HFMD groups were significantly decreased ( F=23. 23, 30. 88,10. 766,11. 680 respectively;P<0. 05) . However the frequency of Th17 cells,serum levels of IL?6,IL?17,IL?23 in severe HFMD groups were significantly increased( F=646. 81,5. 904,10. 557,3. 490 respectively;P<0. 05) . Conclusion The changes of Treg and Thl7 cells and related cytokines appear in peripheral blood of patients with HFMD in the initial stage of infection caused by Enterovirus 71 virus. The frequency of Treg cell is decreased,however,the frequency of Thl7 cells frequency is increased,as a result,which may spread inflammato?ry reaction and cause complication.
ABSTRACT
Objective To study the effects of EP4 and EP2 antagonists on the differentiation of Treg/ Th17 cells and disease progression in mice of collagen-induced arthritis (CIA) model.Methods DBA/1 mice wereimmunized subcutaneously twice at the root of the tail with type Ⅱ collagen emulsified in Freund's complete adjuvant.EP2 and EP4 antagonist therapies were intraperitoneally administrated for 14 consecutive days after the second immunization.Clinical signs,histological manifestation,serum interleukin (IL)-17 and quantity of CD4+CD25+Foxp3+ Treg cells were determined.ANOVA and t-test were used for statistical analysis.Results Clinical signs of the disease appeared on day 27 and peaked on day 35 after the first immunization.The quantity of CD4+CD25+Foxp3+ Treg cells in spleens [(1.67±0.15)％] and draining inguinal lymph nodes [(3.30±0.36)％] isolated from CIA mice were significantly lower than those of normal DBA/1 mice [(2.77±0.45)％ and (4.73 ±0.45)％ respectively,P＜0.05].Serum IL-17 level of CIA mice [(27±7) pg/ml] was significantly higher than that of normal DBA/1 mice [(14±4) pg/ml,P＜0.05].Intra-peritoneal injection of EP4 but not EP2 antagonist to CIA mice decreased paw edema and swelling,and alleviated the histological manifestations (1.8±1.0 vs 3.5±0.6,P＜0.05) on day 35 after the first immunization.The percentages of CD4+CD25+Foxp3+ Treg cells in both inguinal lymph nodes [(4.20±0.32)％] and spleens [(2.63±0.40)％] were significantly higher in EP4 antagonist-treated but not EP2 antagonist-treated CIA mice compared with CIA mice group [(3.30±0.36)％ and (1.67±0.15)％ respectively,P＜0.05].The level of serum IL-17 was significantly lower in EP4 antagonist-treated [(15±7) pg/ml] but not EP2 antagonist-treated CIA mice compared with CIA mice group [(27±7) pg/ml,P＜0.05].Conclusion EP4 antagonist therapy alleviates clinical symptoms of CIA,improves the histological manifestations,decreases the serum IL-17 level and increases the percentages of CD4+CD25+Foxp3+ Treg cells in both spleens and draining inguinal lymph nodes,so targeting EP4 receptor may be a new possible therapeutic possibility in the prevention and treatment of rheumatoid arthritis.
ABSTRACT
Objective To review the pathogenesis and research prospects in AA.[Methods] In this paper, we summarize the imbalance mechanism of Th1/Th2, and the relationship of fol icular helper T cells(Tfh),Thl7, Th9 ,Th22 with aplastic anemia. [Results]The imbalance of Th1/Th2 cells leads to bone marrow failure. Immunosuppressive therapy can inhibit Th1 cell, restore the balance. The pathogenesis of Tfh, Thl7, Th9 and Th22 is closely correlated with AA. [Conclusion] AA pathogenesis is complex, CD4+cellsubsets is related to the occurrence and development of AA. Detect the levels of immune cells in the serum of patients is beneficial for diagnosis and treatment of AA.
ABSTRACT
Objective To further explore the pathogenesis of disturbed adaptive immune response in infants with sepsis. Methods Forty-eight infants with sepsis and 26 age-matched healthy infants were enrolled in this study. The HLA-DR expression of CD14~+ monocyte, the proportion of CD4~+ CD25~+ Foxp3~(high) Tr cells and the proportion of Thl7 cells were measured by flow cytometry. Cytokines (IL-1β, IL-6, TNF-α, IL-10, TGF-β and IL-17A) were measured by ELISA. Real-time PCR were used to evaluate the mRNA levels of Foxp3, ROR-γt in CD4-positive cells and IL-17A. Forty-eight infants with sepsis were divided into two groups according to HLA-DR expression of CD14~+ monocyte: DR-H group ( ＞ 30% ) and DR-L group ( ＜ 30% ). Results The ratio of IL-10/TNF-α in DR-L group was higher than that in healthy control or DR-H group(P ＜0.05). The proportion of CD4~+ CD25~+ Foxp3~(high) Tr cells and mRNA expression of transcription factor Foxp3 in DR-L group was found to be significantly higher than that in healthy control or DR-H group(P＜0.05). The proportion of Thl7 cells, Serum concentration of IL-17A, the mRNA expression of IL-17A and transcription factor ROR-γt were significantly increased in DR-H group and DR-L group (P ＜ 0.05) , while there is no significant difference between DR-H and DR-L group( P ＞0.05). Serum levels of Th17-inducing cytokine such as IL-1β, IL-6 were significantly elevated in DR-H group and DR-L group (P＜0.05), while there is no significant difference between DR-H and DR-L group( P＞0.05). Serum level of CD4~+ CD25~+ Foxp3~(high) Tr-inducing cytokine TGF-p in DR-L group was higher than that in DR-H or healthy control group(P＜0. 05). Conclusion Over-activation of Th17 cells may be one of the factors causing aberrant increase of pro-inflammatory cytokine/chemotatic factor in infant with sepsis. The imbalance of CD4~+ CD25~+ Foxp3~(high) Tr cells/Th17 cells may be contributed to the pathogenic mechanism of mixed antagonist response syndrome ( MARS) in infant with sepsis. The changes of cytokine environment in infants with sepsis may be one of the factors causing the imbalance of CD4~+ CD25~+ Foxp3~(high) Tr cells/Th17 cells.