Objective To investigate the possible mechanism of high mobility group box 1 (HMGB1) involved in the regulation of asthma-related inflammatory cytokines in bronchial epithelial cells. Methods Twenty female mice (BALB/c strain) were randomly divided into control and asthma group.An asthmatic mouse model was established by intraperitoneal injection and aerosol inhalation of ovalbumin.16-HBE cells with different treatments were divided into six groups:control group,HMGB1 group (100 ng/mL,200 ng/mL,500 ng/mL),500 ng/mL HMGB1+AG490 group,500 ng/mL HMGB1+ Rapamycin group.The hematoxylin-eosin staining was used to observe the mice airway structural changes.The mRNA and protein expression of HMGB1 in lung tissue of mice was measured by RT-PCR and immunohistochemistry,respectively.The level of HMGB1 in the supernatants of the BALF and the levels of TNF-α,IL-6 and IL-1α in all cells were measured by ELISA,while the protein expressions of p-JAK2 and p-STAT3 were measured by Western blot. Results Compared with normal control group,the expression of HMGB1 in BALF and in the lung tissue of asthma group were significantly increased.HMGB1 increased the levels of TNF-α,IL-6 and IL-1α,upregulated the protein levels of p-JAK2 and p-STAT3 in a dose-dependent manner.Pretreatment with AG490 and Rapamycin significantly inhibited the expressions of p-JAK2 and p-STAT3,decreased the levels of TNF-α,IL-6 and IL-1α. Conclusion HMGB1 could regulate the inflammatory response in asthma,which may be related to the promotion of asthma-related inflammatory cytokines in bronchial epithelial cells via activating JAK2/STAT3 pathways.
Key words
high mobility group box 1 /
bronchial epithelial cells /
JAK2/STAT3 /
asthma /
inflammatory cytokines
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References
[1] Krogulska A,Polakowska E,Wasowska-Krolikowska K,et al.Decreased FOXP3 mRNA expression in children with atopic asthma and IgE-mediated food allergy[J].Ann Allergy Asthma Immunol,2015,115(5):415-421.
[2] Galobardes B,Granell R,Sterne J,et al.Childhood wheezing,asthma,allergy,atopy,and lung function:different socioeconomic patterns for different phenotypes[J].Am J Epidemiol,2015,182(9):763-774.
[3] Zhang F,Huang G,Hu B,et al.Recombinant HMGB1 A box protein inhibits Th17 responses in mice with neutrophilic asthma by suppressing dendritic cell-mediated Th17 polarization[J].Int Immunopharmacol,2015,24(1):110-118.
[4] Li YL,Luan B,Qiao JY,et al.Effects of different doses of 1,25-(OH)2D3 on expression of HMGB1 and IL-17 in the lungs of asthmatic mice[J].Zhong Guo Dang Dai Er Ke Za Zhi,2015,17(2):190-195.
[5] Ma L,Zeng J,Mo B,et al.High mobility group box 1:a novel mediator of Th2-type response-induced airway inflammation of acute allergic asthma[J].J Thorac Dis,2015,7(10):1732-1741.
[6] Yang Y,Li S,Yang Q,et al.Resveratrol reduces the proinflammatory effects and lipopolysaccharide- induced expression of HMGB1 and TLR4 in RAW264.7 cells[J].Cell Physiol Biochem,2014,33(5):1283-1292.
[7] Gauthier M,Ray A,Wenzel SE.Evolving concepts of asthma[J].Am J Respir Crit Care Med,2015,192(6):660-668.
[8] Sears MR.Predicting asthma outcomes[J].J Allergy Clin Immunol,2015,136(4):829-836.
[9] Zhao X,Kuja-Panula J,Rouhiainen A,et al.High mobility group box-1 is required for zebrafish brain development[J].J Biol Chem,2011,286(26):23200-23213.
[10] Nomura S,Maeda Y,Ishii K,et al.Relationship between HMGB1 and PAI-1 after allogeneic hematopoietic stem cell transplantation[J].J Blood Med,2016,18(7):1-4.
[11] Dong WW,Liu YJ,Lv Z,et al.Lung endothelial barrier protection by resveratrol involves inhibition of HMGB1 release and HMGB1-induced mitochondrial oxidative damage via an Nrf2-dependent mechanism[J].Free Radic Biol Med,2015,88(Pt B):404-416.
[12] Tang Y,Zhao X,Antoine D,et al.Regulation of Posttranslational Modifications of HMGB1 During Immune Responses[J].Antioxid Redox Signal,2016,24(12):620-634.
[13] Merianda TT,Coleman J,Kim HH,et al.Axonal amphoterin mRNA is regulated by translational control and enhances axon outgrowth[J].J Neurosci,2015,35(14):5693-5706.
[14] Zhang H,Liu Z and Liu S.HMGB1 induced inflammatory effect is blocked by CRISPLD2 via MiR155 in hepatic fibrogenesis[J].Mol Immunol,2016,69(7):1-6.
[15] Shi S,Liang D,Bao M,et al.Gx-50 Inhibits Neuroinflammation via alpha7 nAChR Activation of the JAK2/STAT3 and PI3K/AKT Pathways[J].J Alzheimers Dis,2016,50(3):859-871.
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