| Background:Bronchial asthma(asthma),with pathological features of airway inflammation and airway remodeling,is a chronic inflammatory disease characterized by variable and reversible airflow limitation and airway hyperresponsiveness(AHR).In patients of asthma,airway remodeling results in pathological changes including AHR and irreversible airflow limitation,which is responsible for the impaired lung function.In general,airway remodelling is composed of thickening of airway wall and deposition of extracellular matrix(ECM),neoangiogenesis,hyperplasia and hypertrophy of airway smooth muscle(ASM)cells.Although symptoms of asthmatic patients can be effectively controlled,the airway remodeling cannot be preventable or cureable.T lymphocytes play a crucial role in the pathogenesis of asthma with their cytokines.The imbalance of immune response of T helper cells(Th)subsets is closely related to the pathogenesis of asthma and Th1/Th2 imbalance is an important factor.The precise regulation of the Th1/Th2 balance and the downstream of signaling pathways involved in Th1 and Th2 cells are crucial for maintenance of pulmonary homeostasis as well as development of airway inflammation and airway remodeling in asthmatics.Studies have found that the level of IL-27 in serum changed in patients with acute asthma and it was associated with alterations of lung function.Jirmo AC and colleagues reported that IL-27 enhanced secretion of IFN-y whereas it reduced that of IL-5 and IL-13,demonstrating its direct effect on inhibiting Th2 responses.Their findings provide evidence of an important role of IL-27 for the suppression of allergic asthma.Based on OVA-induced mouse model,Yoshimoto et al.have shown that intranasal administration of IL-27 can reduce OVA-induced airway hyperresponsiveness and inflammation.However,Su X and colleagues have found that preventative intranasal administration of IL-27 alleviates airway inflammation and improves the pathological changes while therapeutic administration of IL-27 does not have effects on AHR and airway inflammation due to already differentiated Th2 cells which exist in airways and resist to IL-27-mediated Th2 development.Furthermore,it has not been studied whether IL-27 occupies a role in airway remodeling in chronic model of asthma.Moreover,current studies have focused on not the effect of IL-27 on airway remodeling but the airway inflammation.As a pathological feature of asthma,airway remodeling has not been well studied.In addition,whether therapeutic administration of IL-27 can reduce airway inflammation,AHR,and other pathological process in asthmatic model of mice is still inconsistent.Furthermore,it is still controversial by which signaling pathway IL-27 can have a role in inhibiting airway inflammation as well as AHR.Finally,there is so far no literature on whether IL-27 has an effect on airway remodeling.Objective:To investigate whether preventative and therapeutic administration of IL-27 could inhibit airway inflammation,airway hyperresponsiveness and airway remodeling in models of asthmatic mice.If they can be inhibited,signaling pathways by which IL-27 plays a role are also examined.This research may shed light on administration of IL-27,which has the potential to be used as an intervention for asthma and provide a new target for the prevention and management of airway remodeling in asthmatics.Methods:1.Female BALB/c mice aged 6 weeks were sensitized and challenged with chicken egg ovalbumin(OVA)and acute plus chronic models of experimental asthma in mice were set up.In the preventative treatment group,mice were divided into normal PBS group(PBS),OVA group(OVA)and IL-27 Preventative treatment group(OVA+IL-27)at random and they were randomized to normal PBS group(PBS),OVA group(OVA)and IL-27 Therapeutic treatment group(OVA+IL-27)in the therapeutic treatment group.Each group had 8 mice.2.Bronchoalveolar lavage of fluid(BALF)from mice were collected.The total and differential cell counts were determined on cytocentrifuged preparations(Cytospin)after staining with Wright-Giemsa,including cell counts of neutrophils(Neu),monocytes(Mon),lymphocytes(Lym),eosinophils(Eos)and basophils(Bas).3.The concentrations of IL-4,IL-5,IL-13,IL-17 and IFN-y in serum and supernatant of BALF from mice were ascertained by enzyme-linked immuno sorbent assay(ELISA).4.Airway resistance and airway compliance were detected by an invasive pulmonary function analysis system.5.The expressions of mRNA for STAT1,STAT3,GATA-binding protein-3(GATA-3)and transcription factors T-box expressed in T-cells(T-bet)in lung tissues of mice were probed using Real-time PCR.6.The expressions of proteins for STAT1,phosphorylated STAT1(p-STAT1),STAT3,p-STAT3,GATA-3 and T-bet in lung tissues of mice were examined by Western blot.The ratio of p-STAT1 to STAT1 and that of p-STAT1 to STAT1 were also calculated.7.Airway remodeling in lung tissues was evaluated by various staining methods:1)The area of airway wall(Wat),area of smooth muscle(Wam)and the perimeter of basement membrane(Pbm)were measured and the averages were calculated using image analysis software based on lung tissue sections stained with hematoxylin and eosin(H&E).The airway wall thickening and smooth muscle hyperplasia were determined by the ratio of Wat to Pbm(Wat/Pbm)(?m2/?m)and that of Wam to Pbm(Wam/Pbm)(?m2/?m).2)The measurement of area with blue collagen deposition under basement membrane was done and the average of the area was calculated by image analysis software according to lung tissue sections stained with Masson's trichrome stain.The degree of collagen deposition was evaluated by the area of Masson's trichrome-positive stained per um of Pbm.3)The area of periodic-acid schiff(PAS)-positive stained(PAS+)was surveyed and the calculation of the averaged area was gotten by image analysis software on the basis of lung tissue sections stained with PAS stain.The level of hyperplasia of goblet cells was examined by the area of PAS+divided by Pbm.4)The quantificational level of area with peribronchial ?-SMA immunostaining(?-SMA+)was obtained by using image analysis software based on lung tissue sections.The extent of activation of myofibroblast was estimated by the area of ?-SMA+ per um of Pbm.5)The degree of area with peribronchial CD31 immunostaining(CD31+)was evaluated using image analysis software according to lung tissue sections.The level of the angiogenesis in the airway wall was assessed by the area of CD31+divided by Pbm.Results:1.The clinical manifestations of asthmatic mice induced by OVAThe mice in the asthmatic model group(OVA group)showed obvious symptoms of asthma attack immediately after inhalation of OVA,such as dysphoria,dyspnea,convulsion of abdominal muscle,more activity,urinary and fecal incontinence,hair raising.Some mice have abnormal manifestations such as wheeze,lags in response and slow movements.These indicate asthmatic model of mice were successfully made.2.The total and differential cell counts in BALF of mice2.1 The total cell counts in BALF of mice2.1.1 IL-27 decreased the total number of cells in BALF in mice of Preventative treatment group The total number of cells(×104 cells/ml)in BALF was significantly different among the three groups(PBS group:8.38±1.94,OVA group:190.70±29.77,OVA+IL-27 group:99.94±17.31,F=167.60,P<0.001,one-way ANOVA).The total cell number in BALF in the OVA+IL-27 group was significantly lower than that in the OVA group(t=9.11,P<0.001,Bonferroni's Multiple Comparison Test).2.1.2 IL-27 did not reduce the total number of cells in BALF in mice from Therapeutic treatment groupThe total number of cells(×104 cells/ml)in BALF of the three groups was significantly different(PBS group:8.59±2.07,OVA group:193.50±40.35,OVA+IL-27 group:152.50±40.31,F=69.52,P<0.001,one-way ANOVA).There was no significant difference in total cell counts of BALF between the OVA group and the OVA+IL-27 group(t=2.49,P>0.05,Bonferroni's Multiple Comparison Test).2.2 The differential cell counts in BALF of mice2.2.1 IL-27 can reduce the numbers of different inflammatory cells in BALF of mice in Preventative treatment groupThere were significant differences in the number of Monocytes(Mon)(×104 cells/ml)in BALF of the three groups of mice(PBS group vs OVA group vs OVA+IL-27 group,the same below:4.53±1.77 vs 17.82±5.18 vs 10.40±2.36,F=29.95,P<0.001,one-way ANOVA,the same below),Eosinophil(Eos)(0.47±0.25 vs 61.99±19.77 vs 17.22±4.36,F=59.26,P<0.001),Neutrophil(Neu)(2.31±1.04 vs 27.79±6.17 vs 15.91±4.34,F=67.20,P<0.001),Lymphocyte(Lym)(0.97±0.35 vs 78.23±15.32 vs 69.44±19.56,F=69.54,P<0.001)and Basophil(Bas)(0.37±0.08 vs 6.03±1.76 vs 1.89±0.49,F=61.51,P<0.001)among the three groups of mice.The cell numbers of Mon(t=4.31,P<0.001,Bonferroni's Multiple Comparison Test,same as below),Eos(t=7.66,P<0.001),Neu(t=5.40,P<0.001),Lym(t=4.43,P<0.001)and Bas(t=7.83,P<0.001)in BALF in the OVA+IL-27 group was significantly lower than those in the OVA group.2.2.2 IL-27 could not diminish the numbers of different inflammatory cells in BALF of mice in Therapeutic treatment groupSignificant differences in the number of Mon(×104 cells/ml)in BALF of the three groups of mice(PBS group vs OVA group vs OVA+IL-27 group,the same below:4.70±1.59 vs 18.01±6.35 vs 13.56±5.14,F=16.01,P<0.001,one-way ANOVA,the same below),Eos(0.50±0.25 vs 62.32±20.52 vs 52.78±13.33,F=44.38,P<0.001),(Neu)(2.34±1.06 vs 28.17±5.78 vs 24.15±4.80,F=80.58,P<0.001),(Lym)(1.01±0.39 vs 74.97±16.53 vs 49.84±10.64,F=87.81?P<0.001)and(Bas)(0.38±0.11 vs 6.23±2.19 vs 4.77±1.59,F=30.18,P<0.001)were found among the three groups of mice.No marked differences were found in the counts of Mon(t=4.31,P<0.001,Bonferroni's Multiple Comparison Test,same as below),Eos(t=7.66,P<0.001),Neu(t=5.40,P<0.001)?Lym(t=4.43,P<0.001)and Bas(t=7.83?P<0.001)in BALF between the OVA group and the OVA+IL-27 group.3.Measurement of airway hyperreactivity(AHR)in mice3.1 IL-27 ameliorated the airway responsiveness to acetylcholine in mice of Preventative treatment groupNo significant differences were found in the baseline airway responsiveness amongst the three groups.When mice were challenged by inhalation of methacholine at a concentration of 20 mg/m],the airway resistance(R)enhanced(2.93±0.17 vs 5.10±0.19,F=285.30,P<0.001,one-way ANOVA;t=9.14,P<0.001,Bonferroni's Multiple Comparison Test)while lung compliance(Cdyn)decreased significantly(0.48±0.02 vs 0.29±0.03,F=171.70,P<0.001,one-way ANOVA;t=10.19,P<0.001,Bonferroni's Multiple Comparison Test)in OVA-challenged mice compared with that in PBS-challenged ones.The airway responses to methacholine challenge in the OVA+IL-27 group were pronouncedly lower compared to those in the OVA group.Compared to the OVA group,there were significant decreases in R(5.10±0.19 vs 4.26±0.19?F=285.30,P<0.001,one-way ANOVA;T=9.14,P<0.001?Bonferroni's Multiple Comparison Test)and increases in Cdyn(0.29±0.03 vs 0.39±0.02,F=171.70,P<0.001,one-way ANOVA,T=10.19,P<0.001,Bonferroni's Multiple Comparison Test)in the OVA+IL-27 group when mice were challenged by inhalation of methacholine at a concentration of 20 mg/ml.3.2 IL-27 did not improve the airway responsiveness to acetylcholine in mice of Therapeutic treatment groupNo marked differences were found in the baseline airway responsiveness amongst the three groups.When mice were challenged by inhalation of methacholine at a concentration of 20 mg/ml,the R enhanced(2.94±0.44 vs 5.02±0.20,F=111.10,P<0.001,one-way ANOVA;t=14.00,P<0.001,Bonferroni's Multiple Comparison Test)while Cdyn decreased significantly(0.49±0.02 vs 0.29±0.03,F=175.80,P<0.001,one-way ANOVA;t=17.37,P<0.001,Bonferroni's Multiple Comparison Test)in OVA-challenged mice compared to that in PBS-challenged mice.There were no significant differences in the airway responses to methacholine challenge between the OVA+IL-27 group and the OVA group.When mice were challenged by inhalation of methacholine at a concentration of 20 mg/ml,no significant diminishment of R(5.02±0.20 vs 4.64±0.18,F=111.10,P<0.001,one-way ANOVA;t=2.56,P>0.05,Bonferroni's Multiple Comparison Test)and enhancement of Cdyn(0.29±0.03 vs 0.32±0.02,F=175.80,P<0.001,one-way ANOVA;t=2.56,P>0.05,Bonferroni's Multiple Comparison Test)were found between the OVA group and the OVA+IL-27 group.4.The concentrations of IL-4,IL-5,IL-13,IL-17 and IFN-? in supernatant of BALF in the acute asthma model of mice4.1 IL-27 decreased the levels of IL-4,IL-5,IL-13 and IL-17 in BALF of mice while increased that of IFN-yin Preventative treatment groupThere were significant differences in the level of IL-4(pg/ml)(PBS group vs OVA group vs OVA+IL-27 group,the same below:60.03±13.34 vs 134.20±26.59 vs 101.60±21.90,F=24.30,P<0.001,one-way ANOVA,the same as below),IL-5(39.33±9.75 vs 84.52±14.70 vs 62.68±12.97,F=25.58,P<0.001),IL-13(122.90±26.79 vs 369.50±100.40 vs 244.60168.97,F=23.48,P<0.001),IL-17(67.61±12.13 vs 203.50±38.32 vs 142.20±22.99,F=51.84,P<0.001)and IFN-?(80.22±18.45 vs.39.99±9.21 vs 59.87±14.82,F=15.06,P<0.001)among the three groups of mice.Compared with the OVA group,the concentrations of IL-4(t=3.06,P<0.05,Bonferroni's Multiple Comparison Test,the same below),IL-5(t=3.46,P<0.05),IL-13(t=3.47,P<0.05),and IL-17(t=4.59,P<0.01)in serum of mice significantly decreased and that of IFN-y(t=2.71,P<0.05)significantly increased in the OVA+IL-27 group.4.2 Il-27 did not affect levels of IL-4,IL-5,IL-13,IL-17 and IFN-?in BALF of mice in Therapeutic treatment groupSignificant differences in the level of IL-4(pg/ml)(PBS group vs OVA group vs OVA+IL-27 group,the same as below:58.96±15.47 vs 130.00±30.39 vs 104.60±26.14,F=16.84,P<0.001,one-way ANOVA,the same below),IL-5(39.80±11.32 vs 79.61±23.60 vs 63.87±18.53,F=9.38,P<0.001),IL-13(117.50±34.18 vs 380.00±87.13 vs 285.20±87.69,F=25.77,P<0.001),IL-17(68.25±17.66 vs 215.80±46.22 vs 177.20±26.43,F=44.66,P<0.001)and IFN-?(68.25±17.66 vs 215.80±46.22 vs 177.20±26.43,F=44.66,P<0.001)were found among the three groups of mice.Evident reductions in the concentrations of IL-4(t=2.05,P>0.05,Bonferroni's Multiple Comparison Test,the same below),IL-5(t=1.70,P>0.05),IL-13(t=2.56,P>0.05),and IL-17(t=2.39,P>0.05)and increase in that of IFN-y(t=0.99,P>0.05)were no longer found between the OVA group and the OVA+IL-27 group.5.The concentrations of IL-4,IL-5,IL-13,IL-17 and IFN-? in serum in three groups of the acute asthma model of mice5.1 IL-27 decreased the levels of IL-4,IL-5,IL-13 and IL-17 in serum of mice while increased that of IFN-yin Preventative treatment groupThere were significant differences in the level of IL-4(pg/ml)(PBS group vs OVA group vs OVA+IL-27 group,the same as below:24.21±8.74 vs 110.60±20.39 vs 66.98±17.00,F=57.36,P<0.001,one-way ANOVA,the same below),IL-5(24.23±8.15 vs 82.87±18.42 vs 53.97±12.36,F=36.96,P<0.001),IL-13(122.90±26.79 vs 369.50±100.40 vs 244.60±68.97,F=23.48,P<0.001),IL-17(46.00±15.44 vs 215.80±46.22 vs 177.20±26.43,F=44.66,P<0.001)and IFN-?(58.81±9.05 vs 32.76±9.55 vs 50.08±10.28,F=15.13,P<0.001)among the three groups of mice.Compared with the OVA group,the concentrations of IL-4(t=5.41,P<0.01,Bonferroni's Multiple Comparison Test,the same below),IL-5(t=4.24,P<0.01),IL-13(t=4.06,P<0.05),and IL-17(t=4.98,P<0.01)in serum of mice significantly decreased and that of IFN-y(t=3.59,P<0.01)significantly increased in the OVA+IL-27 group.5.2 Il-27 could not affect levels of IL-4,IL-5,IL-13,IL-17 and IFN-?in serum of mice in Therapeutic treatment groupSignificant differences in the level of IL-4(pg/ml)(PBS group vs OVA group vs OVA+IL-27 group,the same as below:26.25±12.01 vs 100.40±28.67 vs 80.58±24.13,F=22.84,P<0.05,one-way ANOVA,the same as below),IL-5(26.86±9.26 vs 79.57±19.31 vs 61.55±15.80,F=24.31,P<0.001),IL-13(149.90±39.42 vs 439.40±101.10 vs 345.40±112.20,F=21.48,P<0.001),IL-17(46.00±15.44 vs 157.70±37.82 vs 126.50±33.26,F=28.75,P<0.001)and IFN-?(59.96±12.06 vs 33.84±12.47 vs 44.84±12.39,F=9.07,P<0.001)were found among the three groups of mice.However,no evident reductions in the concentrations of IL-4(t=1.74,P>0.05,Bonferroni's Multiple Comparison Test,the same below),IL-5(t=2.35,P>0.05),IL-13(t=2.09,P>0.05),and IL-17(t=2.05,P>0.05)and increase in that of IFN-y(t=1.79,P>0.05)in the OVA+IL-27 group were observed in comparison with those in the OVA group.6.The expressions of mRNA for STAT1,STAT3,T-bet and GATA-binding protein-3(GATA3)in lung tissues of the mice6.1 IL-27 enhanced the expressions of STAT1mRNA and T-bet mRNA while decreased that of GATA3 mRNA in lung tissues of mice in Preventative treatment groupThere were significant differences in the expression of STAT1 mRNA(PBS group vs OVA group vs OVA+IL-27 group,the same below:0.94±0.21 vs 0.67±0.19 vs 1.04±0.32,F=4.61,P<0.05,one-way ANOVA,the same below),GATA3 mRNA(1.15±0.39 vs 5.06±0.83 vs 2.93±0.90,F=55.30,P<0.01)and T-bet mRNA(0.97±0.29 vs 0.31±0.11 vs 0.62±0.25,F=16.83,P<0.001)among the three groups of mice.No significant differences in the expressions of STAT3 mRNA(0.99±0.25 vs 0.73±0.24 vs 0.88±0.25,F=2.14,P>0.05)were found amongst the three groups of mice.Compared with the OVA group,the expressions of STAT1 mRNA(t=2.70,P<0.05,Bonferroni's Multiple Comparison Test,the same below)and t-bet mRNA(t=2.72,P<0.05)significantly upregulated and that of GATA3 mRNA(t=9.72,P<0.01)significantly downregulated in the OVA+IL-27 group.No significant differences in the expressions of STAT3 mRNA(t=1.21,P>0.05)exsits between the OVA group and the OVA+IL-27 group.6.2 IL-27 had no effect on the expressions of STAT1 mRNA,STAT3 mRNA,T-bet mRNA and GATA3 mRNA in the lung tissues of mice in Therapeutic treatment groupNo significant differences in the expressions of STAT1 mRNA(PBS group vs OVA group vs OVA+IL-27 group,the same below:1.04±0.23 vs 0.94±0.13 vs 1.03±0.16,F=0.74,P>0.05,one-way ANOVA,the same below)and STAT3 mRNA(1.00±0.25 vs 0.79±0.33 vs 0.88±0.23,F=1.26,P>0.05)were found among the three groups of mice.For the expression of both GATA3 mRNA(0.98±0,34 vs 5.56±1.42 vs 4.37±1.36,F=34.04,P<0.01)and T-bet mRNA(0.96±0.29 vs 0.45±0.14 vs 0.64±0.22,F=9.85,P<0.01),there were pronounced disparities amongst the three groups of mice.However,there were no significant differences in the expression of STAT1 mRNA(t=0.98,P>0.05,Bonferroni's Multiple Comparison Test,the same below),STAT3 m RNA(t=0.67,P>0.05),GATA3 mRNA(t=2.07,P>0.05)and T-bet mRNA(t=1.62,P<0.05)between the OVA group and the OVA+IL-27 group.7.Expression of proteins for STAT1,phosphorylated STAT1,STAT3,phosphorylated STAT3,T-bet and GATA3 in lung tissues of mice7.1 IL-27 increased the protein expressions of STAT1,p-STAT1,p-STAT3 and T-bet whereas decreased that of GATA3 in the lung tissues of mice in Preventative treatment group?-actin was used as the internal control.There were significant differences in the expression of STAT1 protein(PBS group vs OVA group vs OVA+IL-27 group,the same as below:0.42±0.17 vs 0.39±0.13 vs 0.63±0.22,F=4.24,P<0.05,one-way ANOVA,the same below),phosphorylated STAT1(p-STAT1)protein(0.99±0.21 vs 0.49±0.11 vs 0.76±0.13,F=31.62,P<0.01),p-STAT3 protein(1.15±0.25 vs 0.40±0.17 vs 0.96±0.31,F=19.64,P<0.01),T-bet protein(0.80±0.12 vs 0.34±0.11 vs 0.50±0.09,F=16.83,P<0.001)and GATA3 protein(1.19±0.24 vs 3.12±0.95 vs 2.03±0.40,F=19.95,P<0.001)among the three groups of mice.Further,significant differences in the ratios of p-STAT1 to STAT1(p-STAT1/STAT1)(2.61±0.79 vs 1.04±0.30 vs 1.78±0.53,F=15.45,P<0.01)and p-STAT3 to STAT3(p-STAT3/STAT3)(1.85±0.53 vs 0.69±0.33 vs 1.36±0.38,F=15.59,P<0.01)were also found among the three groups of mice.In comparision with the OVA group,the expressions of STAT1 protein(t=2.63,P<0.05,Bonferroni's Multiple Comparison Test,the same as below),p-STAT1 protein(t=4.83,P<0.01),p-STAT3 protein(t=4.54,P<0.01)and T-bet protein(t=2.72,P<0.05)in the lung tissues of mice of OVA+IL-27 group upregulated significantly,while the expression of GAT A3 protein downregulated significantly(t=3.56,P<0.05).Compared with the OVA group,p-STAT1/STAT1(t=2.69,P<0.05)and p-STAT3/STAT3(t=3.21,P<0.05)increased strikingly.No markedly disparity in the expression of protein for STAT3was found among the three groups of mice.7.2 IL-27 did not alter the protein expressions of STAT1,STAT3,GATA3 and T-bet in the lung tissues of mice in Therapeutic treatment groupNo significant differences in the expressions of STAT1 protein(PBS group vs OVA group vs OVA+IL-27 group,the same as below:0.45±0.17 vs 0.41±0.12 vs 0.49±0.13,F=0.92,P>0.05,one-way ANOVA,the same below)and STAT3 protein(0.71±0.21 vs 0.68±0.23 vs 0.74±0.18,F=0.13,P>0.05)were found among the three groups of mice.Further,no significant differences in the ratios of p-STATl to STATl(p-STAT1/STAT1)(2.83±1.79 vs 1.50±0.96 vs 1.52±0.80,F=2.92,P>0.05)and p-STAT3 to STAT3(p-STAT3/STAT3)(1.56±0.51 vs 1.36±0.85 vs 1.42±0.54,F=0.19,P>0.05)were found among the three groups of mice.However,there were significant differences in the expressions of p-STAT1 protein(1.15±0.25 vs 0.76±0.11 vs 0.98±0.20,F=7.87,P<0.01),p-STAT3 protein(1.15±0.25 vs 0.76±0.11 vs 0.98±0.20,F=7.87,P<0.01),T-bet protein(0.79±0.14 vs 0.41±0.12 vs 0.56±0.14,F=17.15,P<0.001)and GATA3 protein(1.25±0.32 vs 3.46±0.83 vs 2.69±0.66,F=24.45,P<0.001)among the three groups of mice.No significant differences in the expressions of p-STAT1 protein(t=1.34,P>0.05,Bonferroni's Multiple Comparison Test,the same below),p-STAT3 protein(t=2.23,P>0.01),T-bet protein(t=2.27,P>0.05),GATA3 protein(t=2.41,P>0.05),and p-STAT1/STAT1(t=2.69,P<0.05)and p-STAT3/STAT3(t=3.21,P<0.05)between the OVA group and the OVA+IL-27 group.8.Effects of IL-27 on airway remodeling in chronic mouse model of asthma8.1 IL-27 could attenuate airway remodeling in mice with chronic asthma in Preventative treatment groupThe measurements of Wat/Pbm(?m2/?m)(PBS group vs OVA group vs OVA+IL-27 group,the same as below:3.59±1.42 vs 8.49±2.86 vs 5.38±2.21,F=9.78,P<0.001,one-way ANOVA,the same below)and Wam/Pbm(?m2/?m)(10.22±4.02 vs 24.87±6.44 vs 17.00±5.77,F=14.20,P<0.001)in H&E-stained lung sections,the area of Masson's trichrome-positive stained per um of Pbm(?m2/?m)(1.25±0.41 vs 3.79±0.97 vs 2.39±0.92,F=19.84,P<0.001),the area of PAS+divided by Pbm(?m2/?m)(0.36±0.18 vs 3.06±1.53 vs 1.31±0.92,F=14.05,P<0.001),the area of a-SMA+per um of Pbm(0.69±0.32 vs 2.74±1.21 vs 1.56±0.75,F=11.92,P<0.001)and the area of CD31+ divided by Pbm(0.002±0.001 vs 0.37±0.15 vs 0.19±0.12,F=22.50,P<0.001)all exhibited significant differences among the three groups of mice.Compared with the OVA group,the Wat/Pbm(t=2.77,P<0.05,Bonferroni's Multiple Comparison Test,the same below)and Wam/Pbm(t=2.86,P<0.05)in H&E-stained lung sections,the ratio of Masson's+/Pbm(t=3.45,P<0.05),PAS+/Pbm(t=3.37,P<0.05),a-SMA+/Pbm(t=2.79,P<0.05)and CD31+/Pbm(t=3.32,P<0.05)reduced significantly in the OVA+IL-27 group.8.2 IL-27 can not alleviate airway remodeling in mice with chronic asthma in Therapeutic treatment groupEvident disparities exist amongst the three groups of mice in the measurements of Wat/Pbm(?m2/?m)(PBS group vs OVA group vs OVA+IL-27 group,the same below:3.91±1.81 vs 9.13±3.49 vs 6.61±2.38,F=7.75,P<0.01,one-way ANOVA,the same below)and Wam/Pbm(?m2/(?m)(11.31±5.19 vs 26.27±10.23 vs 19.72±6.34,F=7.85,P<0.05)in H&E-stained lung sections,the area of Masson's trichrome-positive stained per um of Pbm(?m2/?m)(1.21±0.35 vs 3.82±1.24 vs 3.09±0.99,F=16.36,P<0.001),the area of PAS+divided by Pbm(?m2/?m)(0.40±0.20 vs 3.53±1.55 vs 2.80±1.18,F=16.66,P<0.001),the area of a-SMA+per um of Pbm(0.73±0.34 vs 3.30±1.58 vs 2.37±1.46,F=8.58,P<0.001)and the area of CD31+ divided by Pbm(0.001±0.001 vs 0.40±0.16 vs 0.29±0.15,F=21.48,P<0.001).Compared to the OVA group,the Wat/Pbm(t=1.91,P>0.05,Bonferroni's Multiple Comparison Test,the same below)and Wam/Pbm(t=1.73,P>0.05)in H&E-stained lung sections,the ratios of Masson's+/Pbm(t=1.57,P>0.05),PAS+/Pbm(t=1.28,P>0.05),a-SMA+/Pbm(t=1.48,P>0.05)and CD31+/Pbm(t=1.72,P>0.05)showed no significant changes in the OVA+IL-27 group.Conclusions:1.IL-27 is responsible for augment of the Th1 immune response and suppression of the Th2 response and it can improve Th1/Th2 cytokine balance in asthmatic mice.2.The intranasally preventive administration of IL-27 could inhibit the airway inflammation,airway hyperresponsiveness,and airway remodeling in experimental model mice with asthma through signaling pathways of both STAT1 and STAT3.3.IL-27 may be a potential approach for the prevention and treatment of asthma. |
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