Downregulation of matrix metalloproteinase-19 induced by respiratory syncytial viral infection affects the interaction between epithelial cells and fibroblasts

Abstract

The present study was designed to examine the expression and function of matrix metalloproteinase-19 (MMP-19), which is downregulated following respiratory syncytial virus (RSV) infection. The diverse expression levels of MMP were examined using a designed cDNA expression array. The expression and secretion of MMP-19 was examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis and ELISA, respectively. The proliferation of epithelial cells and lung fibroblasts were examined using flow cytometry. The epithelial-mesenchymal transition (EMT) was also examined by performing western blot and RT-qPCR analyses. The results of the cDNA assay showed that infection with RSV resulted in the abnormal expression of certain metalloproteinases. Among these, the expression of MMP-19 decreased 3 and 7 days following infection. By using flow cytometric, western blot and RT-qPCR analyses, the present study demonstrated that the downregulation of MMP-19 inhibited the proliferation of epithelial cells, promoted the EMT and induced the proliferation of lung fibroblasts. Taken together, the findings of the present study suggested that the downregulation of MMP-19 following RSV infection may be associated with the development of airway hyper-responsiveness.

Influences of innate immunity, autophagy, and fibroblast activation in the pathogenesis of lung fibrosis

“…Given the importance of prostaglandins in limiting myofibroblast differentiation (55), it is perhaps not surprising that MMP19 Ϫ/Ϫ mice develop more severe lung fibrosis in response to bleomycin (141). In fact, overexpression of MMP19 in lung epithelial cells can limit fibroblast proliferation in coculture (135). When considered along with data presented above, it is interesting to speculate that MMP19 overexpression from epithelial cells promotes the ability of the fibroblasts to form autophagosomes ( 48) as an additional mechanism to limit fibroproliferation.…”

RSV Promotes Epithelial Neuroendocrine Phenotype Differentiation through NODAL Signaling Pathway

“…RSV (A2 type) was stored by the Department of Microbiology, Central South University. 70% confluent of Hela cells was infected with 100 μ L of RSV for 2 h at 37°C [ 14 , 15 ], and then the nonabsorbed virus was removed and washed twice. Thereafter, the cells were cultured in DMEM with 10% FBS.…”

Immunologic and Non-Immunologic Mechanisms Leading to Airway Remodeling in Asthma

“…Moreover, the above-mentioned intracellular signaling pathways can be activated by asthma relevant micro-organisms such as rhinovirus, respiratory syncytial virus (RSV), bacteria, or intracellular parasites [62][63][64][65][66]. However, we are just starting to understand the mechanisms by which these different micro-organisms activate intracellular signaling of host cells and how they use this for their own benefit.…”

“…The fact that micro-organisms activate the same signaling pathways and cytokines as other asthma triggers might explain how they stimulate airway wall remodeling [62,63]. Dependent on the host cell type, there is also evidence that for example RSV directly affect the interaction between mesenchymal cells and epithelial cells [65], and lead to airway hyper-reactivity [66]. The interaction between the tissue forming cells, also called the epithelial-mesenchymal trophic unit, is a key mechanism to understand the origin of airway wall remodeling.…”

“…Thus, a deregulated expression of HSPs might also explain steroid resistance in asthma patients. Other micro-organisms might affect airway smooth muscle cell remodeling by similar mechanisms [62,[64][65][66], but more details need to be investigated.…”