Human bronchial epithelial cells express and secrete MMP-12.
Matrix metalloproteinases (MMPs) degrade extracellular matrix proteins, which may be responsible for enlargement of alveoli in chronic obstructive pulmonary disease (COPD) and remodeling of pulmonary tissue associated with chronic asthma. Here, we provide novel evidence that MMP-12 is expressed and secreted by normal human bronchial epithelial cell cultures (NHBECs) and reveal the regulation of MMP-12 gene expression by tumor necrosis factor-alpha (TNF-alpha), epidermal growth factor (EGF), and interferon gamma (IFN-gamma). Reverse transcription-polymerase chain reaction analyses demonstrated MMP-12 mRNA presence in unstimulated differentiated NHBEC cultures. Cultures stimulated independently with EGF or IFN-gamma failed to alter MMP-12 mRNA abundance, while TNF-alpha, TNF-alpha+EGF, or TNF-alpha+IFN-gamma elicited relatively early (6 h) peak increases in MMP-12 mRNA levels. Western blot analyses specifically indicated the presence of MMP-12 in differentiated NHBEC-conditioned media. These findings indicate that the bronchial epithelium may be an important source of elastolytic activity in COPD and tissue remodeling in chronic asthma.
Wyeth Research, Cardiovascular and Metabolic Diseases, Cambridge, MA 02140, USA.
Mark C
MC
Lavigne
Paresh
P
Thakker
Jason
J
Gunn
Anthony
A
Wong
Joy S
JS
Miyashiro
Aeona M
AM
Wasserman
Shui-Qing
SQ
Wei
Jeffrey W
JW
Pelker
Michiko
M
Kobayashi
Michael J
MJ
Eppihimer
D000388:Air; D001249:Asthma / Q000378:metabolism*; D015153:Blotting, Western; D001980:Bronchi / Q000166:cytology*; D002364:Caseins / Q000737:chemistry; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D053508:Matrix Metalloproteinase 12; D008666:Metalloendopeptidases / Q000378:metabolism*; D009077:Mucins / Q000378:metabolism; D017434:Protein Structure, Tertiary; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D002364:Caseins; D017077:Culture Media, Conditioned; D009077:Mucins; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins; D007371:Interferon-gamma; D008666:Metalloendopeptidases; C507122:MMP12 protein, human; D053508:Matrix Metalloproteinase 12