Abstract Objective To investigate the effect of heat shock factor 1 (HSF1) on airway hyperresponsiveness and airway inflammation in mice with asthma and possible mechanisms. Methods A total of 36 mice were randomly divided into four groups: control, asthma, HSF1 small interfering RNA negative control (siHSF1-NC), and siHSF1 intervention (n=9 each). Ovalbumin (OVA) sensitization and challenge were performed to induce asthma in the latter three groups. The mice in the siHSF1-NC and siHSF1 groups were treated with siHSF1-NC and siHSF1, respectively. A spirometer was used to measure airway responsiveness at 24 hours after the last challenge. The direct count method was used to calculate the number of eosinophils. ELISA was used to measure the serum level of OVA-specific IgE and levels of interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-13 (IL-13), and interferon-γ (IFN-γ) in lung tissues and bronchoalveolar lavage fluid (BALF). Quantitative real-time PCR was used to measure the mRNA expression of HSF1 in asthmatic mice. Western blot was used to measure the protein expression of HSF1, high-mobility group box 1 (HMGB1), and phosphorylated c-Jun N-terminal kinase (p-JNK). Results The asthma group had significant increases in the mRNA and protein expression of HSF1 compared with the control group (P < 0.05). The siHSF1 group had significantly reduced mRNA and protein expression of HSF1 compared with the siHSF1-NC group (P < 0.05). The knockdown of HSF1 increased airway wall thickness, airway hyperresponsiveness, OVA-specific IgE content, and the number of eosinophils (P < 0.05). Compared with the siHSF1-NC group, the siHSF1 group had significantly increased levels of IL-4, IL-5, and IL-13 and significantly reduced expression of IFN-γ in lung tissues and BALF (P < 0.05), as well as significantly increased expression of HMGB1 and p-JNK (P < 0.05). Conclusions Knockdown of HSF1 aggravates airway hyperresponsiveness and airway inflammation in asthmatic mice, and its possible mechanism may involve the negative regulation of HMGB1 and JNK.
WANG Jing,XIN Li-Hong,CHENG Wei et al. Effect of heat shock factor 1 on airway hyperresponsiveness and airway inflammation in mice with allergic asthma[J]. CJCP, 2017, 19(2): 222-228.
WANG Jing,XIN Li-Hong,CHENG Wei et al. Effect of heat shock factor 1 on airway hyperresponsiveness and airway inflammation in mice with allergic asthma[J]. CJCP, 2017, 19(2): 222-228.
Medoff BD,Sauty A,Tager AM,et al.IFN-gamma-inducible protein 10(CXCL10) contributes to airway hyperreactivity and airway inflammation in a mouse model of asthma[J].J Immunol, 2002,168(10):5278-5286.
[6]
Xie J,Zhao J,Xiao C,et al.Reduced heat shock protein 70 in airway smooth muscle in patients with chronic obstructive pulmonary disease[J].Exp Lung Res,2010,36(4):219-226.
[7]
Wirth D,Christians E,Li X,et al.Use of Hsf1(-/-) mice reveals an essential role for HSF1 to protect lung against cadmiuminduced injury[J].Toxicol Appl Pharmacol,2003,192(1):12-20.
[8]
Wirth D,Bureau F,Melotte D,et al.Evidence for a role of heat shock factor 1 in inhibition of NF-kappaB pathway during heat shock response-mediated lung protection[J].Am J Physiol Lung Cell Mol Physiol,2004,287(5):L953-L961.
[9]
Chen S,Zuo X,Yang M,et al.Severe multiple organ injury in HSF1 knockout mice induced by lipopolysaccharide is associated with an increase in neutrophil infiltration and surface expression of adhesion molecules[J].J Leukoc Biol,2012, 92(4):851-857.
[10]
Shi YH,Shi GC,Wan HY,et al.Coexistence of Th1/Th2 and Th17/Treg imbalances in patients with allergic asthma[J].Chin Med J (Engl),2011,124(13):1951-1956.
Venereau E,De Leo F,Mezzapelle R,et al.HMGB1 as biomarker and drug target[J].Pharmacol Res,2016,111:534- 544.
[13]
Hou C,Zhao H,Liu L,et al.High mobility group protein B1(HMGB1) in Asthma:comparison of patients with chronic obstructive pulmonary disease and healthy controls[J].Mol Med,2011,17(7-8):807-815.
[14]
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.
[15]
Hou C,Kong J,Liang Y,et al.HMGB 1 contributes to allergeninduced airway remodeling in a murine model of chronic asthma by modulating airway inflammation and activating lung fibroblasts[J].Cell Mol Immunol,2015,12(4):409-423.
[16]
Tang H,Zhao H,Song J,et al.Ethyl pyruvate decreases airway neutrophil infiltration partly through a high mobility group box 1-dependent mechanism in a chemical-induced murine asthma model[J].Int Immunopharmacol,2014,21(1):163-170.
[17]
Kim HR,Lee DM,Lee SH,et al.Chlorogenic acid suppresses pulmonary eosinophilia,IgE production,and Th2-type cytokine production in an ovalbumin-induced allergic asthma:activation of STAT-6 and JNK is inhibited by chlorogenic acid[J].Int Immunopharmacol,2010,10(10):1242-1248.
[18]
Zhao M,Yang M,Yang L,et al.HMGB1 regulates autophagy through increasing transcriptional activities of JNK and ERK in human myeloid leukemia cells[J].BMB Rep,2011,44(9):601- 606.
[19]
Kim DE,Min KJ,Kim JS,et al.High-mobility group box-1 protein induces mucin 8 expression through the activation of the JNK and PI3K/Akt signal pathways in human airway epithelial cells[J].Biochem Biophys Res Commun,2012,421(3):436- 441.
[20]
Yu Y,Liu M,Zhang L,et al.Heat shock transcription factor 1 inhibits H2O2-induced cardiomyocyte death through suppression of high-mobility group box 1[J].Mol Cell Biochem,2012, 364(1-2):263-269.
