Critical Care Medicine Research
Respiratory syncytial virus (RSV) is a common cause of infantile bronchiolitis, hospitalization, and long-term pulmonary morbidity. RSV-induced lung pathology is characterized by dramatic neutrophil influx, which contributes to epithelial injury, airway plugging and structural lung damage. Current management is entirely supportive, and no therapies are available that target RSV infection or inflammation. Our laboratory is interested in understanding the effects of protease-antiprotease imbalance on airway inflammation and remodeling seen in RSV disease. Specifically, the laboratory is focused on identifying a mechanistic role for protease dysregulation in RSV infection, and protease potentiation as a critical mechanism in RSV infection. We have recently shown that RSV infection of human airway epithelia results in increased matrix metalloproteinase (MMP)-9 release. In addition, we found higher MMP-9 activity in lung secretions of intubated children with RSV bronchiolitis when compared to controls, and a positive correlation between early elevation of MMP-9 and disease severity. Furthermore, MMP-9 inhibition decreased RSV replication both in vitro and in vivo. Studies are also underway to determine if MMP-9 is a modulator of early viral-induced inflammation in seen in the cystic fibrosis airway and lung.
Kong M, Whitley R, Peng N, Oster R, Schoeb TR, Sullender W, Ambalavanan N, Clancy A, Gaggar A, Blalock JE: Matrix Metalloproteinase-9 Mediates RSV Infection in vitro and in vivo. Viruses 2015; 7(8), 4230-4253
Kong M, Clancy J, Peng N, Li Y, Szul T, Xu X, Oster R, Sullender W, Ambalavanan N, Blalock JE, Gaggar A: Pulmonary MMP-9 activity in mechanically ventilated children with RSV disease. Eur Respir J. 2014; 43(4): 1086-1096
Kong M, Maeng P, Hong J, Van Dyke R, Sorscher E, Sullender W, Clancy JP: Respiratory Syncytial Virus Infection Disrupts Monolayer Integrity and Function in Cystic Fibrosis Airway Cells. Viruses 2013; 5(9): 2260-2271
Kong M, Li Y, Oster R, Gaggar A, Clancy JP: Early Elevation of Matrix Metalloproteinase-8 and -9 in Pediatric ARDS is Associated with an Increased Risk of Prolonged Mechanical Ventilation. PLoS One 2011; Volume 6, Issue 8, e22596
For more information contact:
Michele Kong, M.D.
Assistant Professor of Pediatrics
Pediatric Critical Care Medicine
The University of Alabama at Birmingham
CPPI, Suite 102
1600 7th Ave South
Birmingham, AL 35233
Fax: 205-975-6505
Phone: 205-638-9387
Email: mkong@peds.uab.edu