Objective S100A11 is a member of the S100 calcium-binding protein family and has intracellular and extracellular regulatory activities.We previously reported that S100A11 was differentially expressed in the respirator...Objective S100A11 is a member of the S100 calcium-binding protein family and has intracellular and extracellular regulatory activities.We previously reported that S100A11 was differentially expressed in the respiratory tracts of asthmatic rats as compared with normal controls.Here,we aimed to analyze the potential of S100A11 to regulate both allergen-induced airway hyperresponsiveness(AHR)as well as acetylcholine(ACh)-induced hypercontractility of airway smooth muscle(ASM)and contraction of ASM cells(ASMCs).Methods Purified recombinant rat S100A11 protein(rS100A11)was administered to OVA-sensitized and challenged rats and then the AHR of animals was measured.The relaxation effects of rS100A11 on ASM were detected using isolated tracheal rings and primary ASMCs.The expression levels of un-phosphorylated myosin light chain(MLC)and phosphorylated MLC in ASMCs were analyzed using Western blotting.Results Treatment with rS100A11 attenuated AHR in the rats.ASM contraction assays showed that rS100A11 reduced the contractile responses of isolated tracheal rings and primary ASMCs treated with ACh.In addition,rS100A11 markedly decreased the ACh-induced phosphorylation of the myosin light chain in ASMCs.Moreover,rS100A11 also suppressed the contractile response of tracheal rings in calcium-free buffer medium.Conclusion These results indicate that S100A11 protein can relieve AHR by relaxing ASM independently of extracellular calcium.Our data support the idea that S100A11 is a potential therapeutic target for reducing airway resistance in asthma patients.展开更多
Airway hyperresponsiveness (AHR) is a characteristic feature of asthma, and generally correlates with severity of asthma. Understanding the protection mechanism against excessive airway narrowing and how it breaks dow...Airway hyperresponsiveness (AHR) is a characteristic feature of asthma, and generally correlates with severity of asthma. Understanding the protection mechanism against excessive airway narrowing and how it breaks down is fundamental to solving the problem of asthma. In this paper we have proposed a stochastic modeling the airway smooth muscle bundle for reproducing AHR such as an increased sensitivity of the airways to an inhaled constrictor agonist, a steeper slope of the dose-response curve, and a greater maximal response to agonist. A large number N of contractile muscle cells was assumed to repeat themselves in between contraction and relaxation asynchronously. Dynamic equilibrium of statistic physics was applied to the system of ASM bundle. Thus, the relation of dose to response of a piece of ASM bundle was described by Φ=tanh(βH) , where β was Boltzman factor and H represented energy of contraction induced by constrictor agents. Each of adjacent pair contractile cells was assumed to have Ising-type of antimagnetic interactions of preference energy J (for the condition of contraction-relaxation) between them. A motion equation for a piece of ASM bundle was described by Φ=N(H-zJΦ , which explained existence of combined tonic and phasic contractions. Based on observations of Venegas et al. [4], airway responsiveness was assumed to be assessable by total volume of the ventilation defects (TVD) of 13NN PET-CT images. Interactions via propagation of Ca ion waves between ASM bundles would cause percolation probability by PΦ=(1+tanh(βH))2/4 along the tree, then the relation of dose βH to TVD was described by TVD=PΦ[1-(1-PΦ)3/PΦ3]-TVD0. TVD0 represented the protection mechanism against excessive airway narrowing, which was determined by the ratio of amplitudes between tonic and phasic contractions, thus the balance of amplitudes between tonic and phasic contractions of peripheral lobular smooth muscles would be the determinant of AHR.展开更多
Objectives’ To observe the effects of reflux esophagitis(RE) on the lung function and alrway reactivity,and study the mechanism of airway hyperresponsiveness(AHR) in patients with RE.Methods. Lung function measuremen...Objectives’ To observe the effects of reflux esophagitis(RE) on the lung function and alrway reactivity,and study the mechanism of airway hyperresponsiveness(AHR) in patients with RE.Methods. Lung function measurements and airway provocation tests were performed in 31 RE patientsand 35 control subjects’ TXB, and PGF,. were determined in 20 cases of each group.Results. In RE patients the lung function was lower and the rate of AHR was higher than control sub-jects (P<0. 05). Among RE patients 25 % had higher airway sensitivity (Dminr 3u ). The TXB2 of REpatients with AHR was higher than those without AHR’ Dmin correlated significantly with TXB2 (r=0. 653, P<0. 05).Concluswhs’ RE could damage the lung function. The rate of AHR was 61 %, the high airway sensltivity was probably potential asthma, and TXB2 may play a role in the pathogenesis of AHR.展开更多
目的:观察小青龙汤加减治疗小儿支原体肺炎的临床疗效。方法:将92例小儿支原体肺炎患者按照随机数字表法分为对照组和研究组,每组46例。对照组给予常规治疗,肺炎急性期使用布地奈德雾化液雾化治疗,肺炎症状缓解期使用孟鲁司特钠咀嚼片...目的:观察小青龙汤加减治疗小儿支原体肺炎的临床疗效。方法:将92例小儿支原体肺炎患者按照随机数字表法分为对照组和研究组,每组46例。对照组给予常规治疗,肺炎急性期使用布地奈德雾化液雾化治疗,肺炎症状缓解期使用孟鲁司特钠咀嚼片口服治疗。研究组在对照组治疗的基础上给予小青龙汤加减治疗。观察两组患者临床疗效、肺功能[用力肺活量(forced vital capacity,FVC)、最大呼气流速(peak expiratory flow,PEF)以及第1秒用力呼气容积(forced expiratory volume in the first second,FEV1)]、气道高反应性、复发情况,并检测血清白细胞介素(interleukin,IL)-4、IL-5与外周血嗜酸性粒细胞(eosinophil,EOS)水平。结果:研究组有效率91.30%,对照组有效率为76.09%,研究组有效率高于对照组,差异有统计学意义(P<0.05)。研究组治疗后FVC、PEF、FEV1水平高于对照组,差异有统计学意义(P<0.05)。研究组治疗后最小诱发累积量、促使气道阻力增加至基础值的135%所需要的组胺累积剂量高于对照组,差异有统计学意义(P<0.05)。研究组治疗后血清IL-4、IL-5与外周血EOS低于对照组,差异有统计学意义(P<0.05)。研究组复发率为19.05%(8/42),对照组复发率为42.86%(15/35),研究组复发率低于对照组,差异有统计学意义(P<0.05)。结论:小青龙汤加减治疗治疗小儿支原体肺炎,能改善患者肺功能,减轻患儿气道高反应性,调节血清IL-4、IL-5水平以及外周血EOS水平,降低复发率。展开更多
目的探讨吸入糖皮质激素对咳嗽变异性哮喘患者AHR、BPT转阴率及LCQ评分的影响。方法将48例咳嗽变异性哮喘患者按就诊顺序随机分为布地奈德组、孟鲁司特钠组、沙丁胺醇组三组,每组各16例,三组患者均予吸氧,清淡饮食、盐酸溴已新片8mg po ...目的探讨吸入糖皮质激素对咳嗽变异性哮喘患者AHR、BPT转阴率及LCQ评分的影响。方法将48例咳嗽变异性哮喘患者按就诊顺序随机分为布地奈德组、孟鲁司特钠组、沙丁胺醇组三组,每组各16例,三组患者均予吸氧,清淡饮食、盐酸溴已新片8mg po tid及对症治疗,在此基础上,布地奈德组予布地奈德100μg吸入bid,孟鲁司特钠组予孟鲁司特钠10mg po qn,沙丁胺醇组予沙丁胺醇100μg吸入bid。疗程均为8周。比较BPT转阴率、抗透明质酸酶反应(AHR)、LCQ评分之间的差异。结果治疗后三组BPT转阴率比较,布地奈德组优于孟鲁司特组(P<0.05),并明显优于沙丁胺醇组P<0.01);治疗后三组AHR均有改善,布地奈德组作用最显著,较孟鲁司特组更具优势(P<0.05)。三组LCQ评分前后差值,布地奈德组较孟鲁司特组及沙丁胺醇组分值减少更显著(P<0.01)。结论吸入糖皮质激素能降低AHR及增加BPT的转阴率,还能有效减少LCQ评分。展开更多
Objective:To evaluate the inflammatory pattern and the interferon(IFN)-γin the bronchial secretion of asthma patients in response to acute cold bronchoprovocation.Material and methods:We enrolled 42 patients with ast...Objective:To evaluate the inflammatory pattern and the interferon(IFN)-γin the bronchial secretion of asthma patients in response to acute cold bronchoprovocation.Material and methods:We enrolled 42 patients with asthma.We assessed asthma by Asthma Control Test,the lung function by spirometry before and after the bronchodilator test,followed by collecting induced sputum.The next day,we collected exhaled breath condensate(EBC)and conducted a 3-minute isocapnic hyperventilation with cold air(IHCA),followed by collecting spontaneously produced sputum.Results:Group 1 included 20 patients with cold airway hyperresponsiveness(CAHR),and group 2 included 22 patients without CAHR.In both groups,a high level of neutrophils in bronchial secretion was observed before and after IHCA.In response to IHCA,the number of epitheliocytes in the sputum decreased to a greater extent in patients of group 1.The baseline epitheliocytes and the concentration of IFN-γafter IHCA had an inverse relationship(r=-0.60;P=0.017).The baseline IFN-γin EBC before and after IHCA was lower in group 1.Airway response to cold exposure directly correlated with IFN-γlevels after IHCA(Rs=0.42;P=0.014).Conclusion:In asthma patients with CAHR,there is a relationship between the persistence of mixed inflammation and the level of IFN-γin the bronchi.IFN-γin response to IHCA is decreased with increased cytokine utilization during cold bronchospasm,which is accompanied by the mobilization of neutrophils and the shift in the cytokine spectrum of the respiratory tract towards the T helper cells(Th)1 immune response.展开更多
Interleukin-5 (IL-5) accompanies the development of airway inflammation and hyperresponsiveness through the activation of eosinophils. Therefore, interference of IL-5 expression in lung tissue seems to be an accepted ...Interleukin-5 (IL-5) accompanies the development of airway inflammation and hyperresponsiveness through the activation of eosinophils. Therefore, interference of IL-5 expression in lung tissue seems to be an accepted approach in asthma therapy. In this study, we designed a small interfering RNA (siRNA) to inhibit the expression of IL-5. The siRNAs against IL-5 were constructed in a lentivirus expressing system, and 1.5×106 IFU (inclusion-forming unit) lentiviruses were administered intratracheally to ovalbumin (OVA)-sensitized murine asthmatic models. Our results show that lentivirus-delivered siRNA against IL-5 efficiently inhibited the IL-5 messenger ribonucleic acid (mRNA) expression and significantly attenuated the inflammation in lung tissue. Significant decrease of eosinophils and inflammatory cells were found in peripheral blood, bronchoalveolar lavage fluid (BALF), and lung tissue. In addition, significant inhibition of airway hyperresponsiveness (AHR) was found in the mice treated with siRNA against IL-5. These observations demonstrate that siRNA delivered by means of the lentivirus system is possibly an efficacious therapeutic approach for asthma.展开更多
Background The down-regulation of constitutive nitric oxide synthase （cNOS） and up-regulation of inducible nitric oxide synthase （iNOS） are associated with the allergen-provocated airway hyperresponsiveness （AHR...Background The down-regulation of constitutive nitric oxide synthase （cNOS） and up-regulation of inducible nitric oxide synthase （iNOS） are associated with the allergen-provocated airway hyperresponsiveness （AHR）. This study aimed to determine whether their alteration also plays an important role in the AHR induced by lipopolysaccharide （LPS）. Methods Hartley male guinea pigs, weighing between 250 g and 350 g, were injected with LPS at a dose of 1 mg/kg every 24 hours for three days. A non-selective NOS inhibitor, N^-nitro-L-arginine methyl ester （L-NAME）, or a selective inducible NOS inhibitor, aminoguanidine （AG）, were used thirty minutes before each injection of LPS. Airway reactions, nitric oxide （NO） production and inflammatory changes were detected 24 hours after the last dose of LPS. Results AG significantly decreased the NO production in the bronchoalveolar lavage fluid （BALF） and sharply reduced the intensity of bronchoconstdction to histamine challenge. L-NAME also significantly decreased the NO production in the BALF, but had no effect on airway reactions or, perhaps, a tendency to enhance the intensity of AHR. Conclusions The data suggest that inducible NOS contributes to the AHR induced by repetitive intraperitoneal LPS, and constitutive NOS was also involved.展开更多
Exposure to particulate matter 2.5(PM2.5)potentially triggers airway inflammation by activating nuclear factor-κB(NF-κB).Sirtuin 2(SIRT2)is a key modulator in inflammation.However,the function and specific mechanism...Exposure to particulate matter 2.5(PM2.5)potentially triggers airway inflammation by activating nuclear factor-κB(NF-κB).Sirtuin 2(SIRT2)is a key modulator in inflammation.However,the function and specific mechanisms of SIRT2 in PM2.5-induced airway inflammation are largely understudied.Therefore,this work investigated the mechanisms of SIRT2 in regulating the phosphorylation and acetylation of p65 influenced by PM2.5-induced airway inflammation and bronchial hyperresponsiveness.Results revealed that PM2.5 exposure lowered the expression and activity of SIRT2 in bronchial tissues.Subsequently,SIRT2 impairment promoted the phosphorylation and acetylation of p65 and activated the NF-κB signaling pathway.The activation of p65 triggered airway inflammation,increment of mucus secretion by goblet cells,and acceleration of tracheal stenosis.Meanwhile,p65 phosphorylation and acetylation,airway inflammation,and bronchial hyperresponsiveness were deteriorated in SIRT2 knockout mice exposed to PM2.5.Triptolide(a specific p65 inhibitor)reversed p65 activation and ameliorated PM2.5-induced airway inflammation and bronchial hyperresponsiveness.Our findings provide novel insights into the molecular mechanisms underlying the toxicity of PM2.5 exposure.Triptolide inhibition of p65 phosphorylation and acetylation could be an effective therapeutic approach in averting PM2.5-induced airway inflammation and bronchial hyperresponsiveness.展开更多
基金This work was supported by the National Natural Science Foundation of China(No.81973952 and No.81774429)the Natural Science Foundation of Shanghai(No.19ZR1451500),and the Yangfan Innovation Project(No.20YF1445300).
文摘Objective S100A11 is a member of the S100 calcium-binding protein family and has intracellular and extracellular regulatory activities.We previously reported that S100A11 was differentially expressed in the respiratory tracts of asthmatic rats as compared with normal controls.Here,we aimed to analyze the potential of S100A11 to regulate both allergen-induced airway hyperresponsiveness(AHR)as well as acetylcholine(ACh)-induced hypercontractility of airway smooth muscle(ASM)and contraction of ASM cells(ASMCs).Methods Purified recombinant rat S100A11 protein(rS100A11)was administered to OVA-sensitized and challenged rats and then the AHR of animals was measured.The relaxation effects of rS100A11 on ASM were detected using isolated tracheal rings and primary ASMCs.The expression levels of un-phosphorylated myosin light chain(MLC)and phosphorylated MLC in ASMCs were analyzed using Western blotting.Results Treatment with rS100A11 attenuated AHR in the rats.ASM contraction assays showed that rS100A11 reduced the contractile responses of isolated tracheal rings and primary ASMCs treated with ACh.In addition,rS100A11 markedly decreased the ACh-induced phosphorylation of the myosin light chain in ASMCs.Moreover,rS100A11 also suppressed the contractile response of tracheal rings in calcium-free buffer medium.Conclusion These results indicate that S100A11 protein can relieve AHR by relaxing ASM independently of extracellular calcium.Our data support the idea that S100A11 is a potential therapeutic target for reducing airway resistance in asthma patients.
文摘Airway hyperresponsiveness (AHR) is a characteristic feature of asthma, and generally correlates with severity of asthma. Understanding the protection mechanism against excessive airway narrowing and how it breaks down is fundamental to solving the problem of asthma. In this paper we have proposed a stochastic modeling the airway smooth muscle bundle for reproducing AHR such as an increased sensitivity of the airways to an inhaled constrictor agonist, a steeper slope of the dose-response curve, and a greater maximal response to agonist. A large number N of contractile muscle cells was assumed to repeat themselves in between contraction and relaxation asynchronously. Dynamic equilibrium of statistic physics was applied to the system of ASM bundle. Thus, the relation of dose to response of a piece of ASM bundle was described by Φ=tanh(βH) , where β was Boltzman factor and H represented energy of contraction induced by constrictor agents. Each of adjacent pair contractile cells was assumed to have Ising-type of antimagnetic interactions of preference energy J (for the condition of contraction-relaxation) between them. A motion equation for a piece of ASM bundle was described by Φ=N(H-zJΦ , which explained existence of combined tonic and phasic contractions. Based on observations of Venegas et al. [4], airway responsiveness was assumed to be assessable by total volume of the ventilation defects (TVD) of 13NN PET-CT images. Interactions via propagation of Ca ion waves between ASM bundles would cause percolation probability by PΦ=(1+tanh(βH))2/4 along the tree, then the relation of dose βH to TVD was described by TVD=PΦ[1-(1-PΦ)3/PΦ3]-TVD0. TVD0 represented the protection mechanism against excessive airway narrowing, which was determined by the ratio of amplitudes between tonic and phasic contractions, thus the balance of amplitudes between tonic and phasic contractions of peripheral lobular smooth muscles would be the determinant of AHR.
文摘Objectives’ To observe the effects of reflux esophagitis(RE) on the lung function and alrway reactivity,and study the mechanism of airway hyperresponsiveness(AHR) in patients with RE.Methods. Lung function measurements and airway provocation tests were performed in 31 RE patientsand 35 control subjects’ TXB, and PGF,. were determined in 20 cases of each group.Results. In RE patients the lung function was lower and the rate of AHR was higher than control sub-jects (P<0. 05). Among RE patients 25 % had higher airway sensitivity (Dminr 3u ). The TXB2 of REpatients with AHR was higher than those without AHR’ Dmin correlated significantly with TXB2 (r=0. 653, P<0. 05).Concluswhs’ RE could damage the lung function. The rate of AHR was 61 %, the high airway sensltivity was probably potential asthma, and TXB2 may play a role in the pathogenesis of AHR.
文摘目的:观察小青龙汤加减治疗小儿支原体肺炎的临床疗效。方法:将92例小儿支原体肺炎患者按照随机数字表法分为对照组和研究组,每组46例。对照组给予常规治疗,肺炎急性期使用布地奈德雾化液雾化治疗,肺炎症状缓解期使用孟鲁司特钠咀嚼片口服治疗。研究组在对照组治疗的基础上给予小青龙汤加减治疗。观察两组患者临床疗效、肺功能[用力肺活量(forced vital capacity,FVC)、最大呼气流速(peak expiratory flow,PEF)以及第1秒用力呼气容积(forced expiratory volume in the first second,FEV1)]、气道高反应性、复发情况,并检测血清白细胞介素(interleukin,IL)-4、IL-5与外周血嗜酸性粒细胞(eosinophil,EOS)水平。结果:研究组有效率91.30%,对照组有效率为76.09%,研究组有效率高于对照组,差异有统计学意义(P<0.05)。研究组治疗后FVC、PEF、FEV1水平高于对照组,差异有统计学意义(P<0.05)。研究组治疗后最小诱发累积量、促使气道阻力增加至基础值的135%所需要的组胺累积剂量高于对照组,差异有统计学意义(P<0.05)。研究组治疗后血清IL-4、IL-5与外周血EOS低于对照组,差异有统计学意义(P<0.05)。研究组复发率为19.05%(8/42),对照组复发率为42.86%(15/35),研究组复发率低于对照组,差异有统计学意义(P<0.05)。结论:小青龙汤加减治疗治疗小儿支原体肺炎,能改善患者肺功能,减轻患儿气道高反应性,调节血清IL-4、IL-5水平以及外周血EOS水平,降低复发率。
文摘目的探讨吸入糖皮质激素对咳嗽变异性哮喘患者AHR、BPT转阴率及LCQ评分的影响。方法将48例咳嗽变异性哮喘患者按就诊顺序随机分为布地奈德组、孟鲁司特钠组、沙丁胺醇组三组,每组各16例,三组患者均予吸氧,清淡饮食、盐酸溴已新片8mg po tid及对症治疗,在此基础上,布地奈德组予布地奈德100μg吸入bid,孟鲁司特钠组予孟鲁司特钠10mg po qn,沙丁胺醇组予沙丁胺醇100μg吸入bid。疗程均为8周。比较BPT转阴率、抗透明质酸酶反应(AHR)、LCQ评分之间的差异。结果治疗后三组BPT转阴率比较,布地奈德组优于孟鲁司特组(P<0.05),并明显优于沙丁胺醇组P<0.01);治疗后三组AHR均有改善,布地奈德组作用最显著,较孟鲁司特组更具优势(P<0.05)。三组LCQ评分前后差值,布地奈德组较孟鲁司特组及沙丁胺醇组分值减少更显著(P<0.01)。结论吸入糖皮质激素能降低AHR及增加BPT的转阴率,还能有效减少LCQ评分。
文摘Objective:To evaluate the inflammatory pattern and the interferon(IFN)-γin the bronchial secretion of asthma patients in response to acute cold bronchoprovocation.Material and methods:We enrolled 42 patients with asthma.We assessed asthma by Asthma Control Test,the lung function by spirometry before and after the bronchodilator test,followed by collecting induced sputum.The next day,we collected exhaled breath condensate(EBC)and conducted a 3-minute isocapnic hyperventilation with cold air(IHCA),followed by collecting spontaneously produced sputum.Results:Group 1 included 20 patients with cold airway hyperresponsiveness(CAHR),and group 2 included 22 patients without CAHR.In both groups,a high level of neutrophils in bronchial secretion was observed before and after IHCA.In response to IHCA,the number of epitheliocytes in the sputum decreased to a greater extent in patients of group 1.The baseline epitheliocytes and the concentration of IFN-γafter IHCA had an inverse relationship(r=-0.60;P=0.017).The baseline IFN-γin EBC before and after IHCA was lower in group 1.Airway response to cold exposure directly correlated with IFN-γlevels after IHCA(Rs=0.42;P=0.014).Conclusion:In asthma patients with CAHR,there is a relationship between the persistence of mixed inflammation and the level of IFN-γin the bronchi.IFN-γin response to IHCA is decreased with increased cytokine utilization during cold bronchospasm,which is accompanied by the mobilization of neutrophils and the shift in the cytokine spectrum of the respiratory tract towards the T helper cells(Th)1 immune response.
基金Project supported by the National Natural Science Foundation of China (Nos. 30560160, 30560048, and 30560149)the Program for the New Century Excellent Talents in University of China (No. NCET-05-0757)the Key Scientific Project of Hainan Province, China (No. 081013)
文摘Interleukin-5 (IL-5) accompanies the development of airway inflammation and hyperresponsiveness through the activation of eosinophils. Therefore, interference of IL-5 expression in lung tissue seems to be an accepted approach in asthma therapy. In this study, we designed a small interfering RNA (siRNA) to inhibit the expression of IL-5. The siRNAs against IL-5 were constructed in a lentivirus expressing system, and 1.5×106 IFU (inclusion-forming unit) lentiviruses were administered intratracheally to ovalbumin (OVA)-sensitized murine asthmatic models. Our results show that lentivirus-delivered siRNA against IL-5 efficiently inhibited the IL-5 messenger ribonucleic acid (mRNA) expression and significantly attenuated the inflammation in lung tissue. Significant decrease of eosinophils and inflammatory cells were found in peripheral blood, bronchoalveolar lavage fluid (BALF), and lung tissue. In addition, significant inhibition of airway hyperresponsiveness (AHR) was found in the mice treated with siRNA against IL-5. These observations demonstrate that siRNA delivered by means of the lentivirus system is possibly an efficacious therapeutic approach for asthma.
文摘Background The down-regulation of constitutive nitric oxide synthase （cNOS） and up-regulation of inducible nitric oxide synthase （iNOS） are associated with the allergen-provocated airway hyperresponsiveness （AHR）. This study aimed to determine whether their alteration also plays an important role in the AHR induced by lipopolysaccharide （LPS）. Methods Hartley male guinea pigs, weighing between 250 g and 350 g, were injected with LPS at a dose of 1 mg/kg every 24 hours for three days. A non-selective NOS inhibitor, N^-nitro-L-arginine methyl ester （L-NAME）, or a selective inducible NOS inhibitor, aminoguanidine （AG）, were used thirty minutes before each injection of LPS. Airway reactions, nitric oxide （NO） production and inflammatory changes were detected 24 hours after the last dose of LPS. Results AG significantly decreased the NO production in the bronchoalveolar lavage fluid （BALF） and sharply reduced the intensity of bronchoconstdction to histamine challenge. L-NAME also significantly decreased the NO production in the BALF, but had no effect on airway reactions or, perhaps, a tendency to enhance the intensity of AHR. Conclusions The data suggest that inducible NOS contributes to the AHR induced by repetitive intraperitoneal LPS, and constitutive NOS was also involved.
基金This work was supported by the following grants:National Natural Science Foundation of China(Nos.31671424,91749108,and 81322004 to Heng MaNo.81200036 to Manling Liu)+1 种基金the Science and Technology Research and Development Program of Shaanxi Province,China(No.2015KW-050 to Heng Ma,No.2019SF-008 to Manling Liu,and No.2018SF-101 to Nan Mu)the Youth Innovation Team of Shaanxi Universities,China(to Heng Ma,Yue Yin,Nan Mu,Yishi Wang).
文摘Exposure to particulate matter 2.5(PM2.5)potentially triggers airway inflammation by activating nuclear factor-κB(NF-κB).Sirtuin 2(SIRT2)is a key modulator in inflammation.However,the function and specific mechanisms of SIRT2 in PM2.5-induced airway inflammation are largely understudied.Therefore,this work investigated the mechanisms of SIRT2 in regulating the phosphorylation and acetylation of p65 influenced by PM2.5-induced airway inflammation and bronchial hyperresponsiveness.Results revealed that PM2.5 exposure lowered the expression and activity of SIRT2 in bronchial tissues.Subsequently,SIRT2 impairment promoted the phosphorylation and acetylation of p65 and activated the NF-κB signaling pathway.The activation of p65 triggered airway inflammation,increment of mucus secretion by goblet cells,and acceleration of tracheal stenosis.Meanwhile,p65 phosphorylation and acetylation,airway inflammation,and bronchial hyperresponsiveness were deteriorated in SIRT2 knockout mice exposed to PM2.5.Triptolide(a specific p65 inhibitor)reversed p65 activation and ameliorated PM2.5-induced airway inflammation and bronchial hyperresponsiveness.Our findings provide novel insights into the molecular mechanisms underlying the toxicity of PM2.5 exposure.Triptolide inhibition of p65 phosphorylation and acetylation could be an effective therapeutic approach in averting PM2.5-induced airway inflammation and bronchial hyperresponsiveness.
