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Published on: April 2, 2014
LPS aggravates lung inflammation induced by RSV by promoting the ERK-MMP-12 signaling pathway in mice
Shenglin Chen1,2,3,4,5,6, Jun Xie1,2,3,4,5,6,7, Keting Zhao1,2
1Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, China.
Background:
RSV can lead to persistent airway inflammation and airway hyperresponsiveness (AHR), and is intimately associated with childhood recurrent wheezing and asthma, but the underlying mechanisms remain unclear. Lipopolysaccharide (LPS) is also implicated in the onset and exacerbation of asthma. However, whether inhalation of LPS can boost airway inflammation induced by RSV is not clear. In this study, we utilized an LPS- and RSV-superinfected mouse model to explore underlying pathogenesis.
Methods:
Mice were infected with RSV on day 0 and inoculated with LPS from day 35 to day 41, samples were collected on day 42. Inflammatory cells, lung histopathology and AHR were measured. Cytokines were detected by ELISA and ERK, JNK, p38 was determined by western blot. MMP408, PD98059, SP600125 and SB203580 were used to inhibit MMP-12, ERK, JNK and p38 respectively.
Results:
LPS exposure superimposed on RSV-infected lungs could lead to more vigorous cellular influx, lung structures damage, augmented AHR and higher MMP-12 levels. Inhibition of MMP-12 or ERK signaling pathway in vivo both diminished LPS-driven airway inflammation and AHR.
Conclusions:
Exposure to LPS in RSV-infected mice is associated with enhanced increases in ERK-MMP-12 expression that translates into increased lung inflammation and AHR. These findings contribute novel information to the field investigating the onset of post-RSV bronchiolitis recurrent wheezing as a result of LPS exposure.
Insights
Respiratory Syncytial Virus (RSV) infection combined with Lipopolysaccharide (LPS) exposure exacerbates airway inflammation and hyperresponsiveness in mice. Targeting the ERK-MMP-12 pathway may reduce these RSV-induced lung issues.
Area of Science:
- Respiratory viral infections
- Immunology
- Pulmonary medicine
Background:
- Respiratory Syncytial Virus (RSV) is linked to persistent airway inflammation, hyperresponsiveness, and childhood asthma.
- Lipopolysaccharide (LPS) is implicated in asthma onset and exacerbation.
- The synergistic effect of RSV and LPS on airway inflammation is not well understood.
Purpose of the Study:
- To investigate the pathogenesis of airway inflammation and hyperresponsiveness in a mouse model superinfected with RSV and LPS.
- To explore the role of the ERK-MMP-12 signaling pathway in this superinfection model.
Main Methods:
- Mice were infected with RSV and subsequently exposed to LPS.
- Evaluated inflammatory cell influx, lung histopathology, and airway hyperresponsiveness (AHR).
- Measured cytokine levels and assessed ERK, JNK, and p38 signaling pathways, using specific inhibitors.
Main Results:
- LPS exposure in RSV-infected lungs led to increased inflammation, lung damage, and augmented AHR.
- Elevated levels of MMP-12 were observed in the superinfected lungs.
- Inhibition of MMP-12 or the ERK signaling pathway reduced LPS-driven airway inflammation and AHR.
Conclusions:
- RSV and LPS co-exposure enhances ERK-MMP-12 expression, increasing lung inflammation and AHR.
- These findings offer insights into the mechanisms of post-RSV bronchiolitis and recurrent wheezing.
- Targeting the ERK-MMP-12 pathway presents a potential therapeutic strategy.
