Abstract：Objective To investigate the effect of annexin A2 (AnxA2) on epithelial growth factor receptor (EGFR)/nuclear factor-κB (NF-κB) signal transduction and mucin expression in human airway epithelial H292 cells treated with Mycoplasma pneumoniae (MP). Methods H292 cells were divided into control group, MP group, NC-siRNA+MP group, and AnxA2 siRNA+MP group. The cells in the MP group were incubated with 5 μg/mL MP antigen for 2 hours. The cells in the NC-siRNA+MP and AnxA2 siRNA+MP groups were transfected with NC-siRNA and AnxA2 siRNA for 24 hours, followed by MP antigen stimulation for 2 hours. The MTT method was used to measure cell viability; quantitative real-time PCR was used to measure the mRNA expression of AnxA2; Western blot was used to measure the protein expression of AnxA2, phosphorylated EGFR (p-EGFR), and phosphorylated p65 NF-κB (p-p65 NF-κB); ELISA was used to measure the secretion of mucin 5AC (MUC5AC) and mucin 5B (MUC5B). Results The MP and NC-siRNA+MP groups had lower cell viability than the control group (P < 0.05). The AnxA2 siRNA+MP group had higher cell viability than the MP and NC-siRNA+MP groups and lower cell viability than the control group (P < 0.05). The MP and NC-siRNA+MP groups had signifcantly higher mRNA and protein expression of AnxA2 than the AnxA2 siRNA+MP group (P < 0.05). Compared with the control group, the MP and NC-siRNA+MP groups had significant increases in the protein expression of p-EGFR, p-p65 NF-κB, MUC5AC, and MUC5B (P < 0.05); the AnxA2 siRNA+MP group had lower protein expression than the MP and NC-siRNA+MP groups, but higher protein expression than the control group (P < 0.05). Conclusions AnxA2 is involved in the airway lesion induced by MP antigen via mediating EGFR/NF-κB signaling activation and mucin expression in human airway epithelial cells.
SHEN Dong-Dong,YUAN Fei,HOU Jiang-Hong. Effect of annexin A2 on EGFR/NF-κB signal transduction and mucin expression in human airway epithelial cells treated with Mycoplasma pneumoniae[J]. CJCP, 2017, 19(7): 820-825.
Meyer Sauteur PM, Van Rossum AM, Vink C. Mycoplasma pneumoniae in children:carriage, pathogenesis, and antibiotic resistance[J]. Curr Opin Infect Dis, 2014, 27(3):220-227.
[3]
Hao Y, Kuang Z, Jing J, et al. Mycoplasma pneumoniae modulates STAT3-STAT6/EGFR-FOXA2 signaling to induce overexpression of airway mucins[J]. Infect Immun, 2014, 82(12):5246-5255.
[4]
Wang Y, Zhu Z, Church TD, et al. SHP-1 as a critical regulator of Mycoplasma pneumoniae-induced inflammation in human asthmatic airway epithelial cells[J]. J Immunol, 2012, 188(7):3371-3381.
[5]
Chaudhary P, Thamake SI, Shetty P, et al. Inhibition of triplenegative and Herceptin-resistant breast cancer cell proliferation and migration by Annexin A2 antibodies[J]. Br J Cancer, 2014, 111(12):2328-2341.
[6]
Yang T, Luo F, Shen Y, et al. Quercetin attenuates airway inflammation and mucus production induced by cigarette smoke in rats[J]. Int Immunopharmacol, 2012, 13(1):73-81.
[7]
Yang J, Yu HM, Zhou XD, et al. Cigarette smoke induces mucin hypersecretion and inflammatory response through the p66shc adaptor protein-mediated mechanism in human bronchial epithelial cells[J]. Mol Immunol, 2016, 69:86-98.
Jutten B, Rouschop KM. EGFR signaling and autophagy dependence for growth, survival, and therapy resistance[J]. Cell Cycle, 2014, 13(1):42-51.
[13]
Ledford JG, Voelker DR, Addison KJ, et al. Genetic variation in SP-A2 leads to differential binding to Mycoplasma pneumoniae membranes and regulation of host responses[J]. J Immunol, 2015, 194(12):6123-6132.
[14]
Arae K, Hirata M, Kurata S, et al. Mycoplasma pneumoniae induces interleukin-8 production via the epidermal growth factor receptor pathway[J]. Microbiol Immunol, 2011, 55(10):748-750.
[15]
Xu R, Li Q, Zhou X, et al. Annexin Ⅱ mediates the neutrophil elastase-stimulated exocytosis of mucin 5ac[J]. Mol Med Rep, 2014, 9(1):299-304.
