TY - JOUR
T1 - Deficiency of matrix metalloproteinase-13 increases inflammation after acute lung injury
AU - Sen, Anita I.
AU - Shiomi, Takayuki
AU - Okada, Yasunori
AU - D'Armiento, Jeanine M.
N1 - Funding Information:
This work was supported by NIH grant HL 086936-01 and Professional Schools Diversity Research Fellowship, Columbia University, 2009. The authors thank the many members of the D’Armiento Laboratory, in particular Tina Zelonina, for all their collaborative efforts, support, and encouragement. Address correspondence to Anita I. Sen, MD, 3959 Broadway CHN 10-24, New York, NY 10032, USA. E-mail: ais13@columbia.edu
PY - 2010/11
Y1 - 2010/11
N2 - Human and animal studies of acute lung injury (ALI) have shown that matrix metalloproteinases (MMPs) play an important role in disease pathogenesis, but despite being detected during ALI, the function of the collagenase MMP-13 in ALI is unknown. To evaluate this role of MMP-13, mice deficient in MMP-13 (KO) were examined after hyperoxic lung injury, and compared to wild-type (WT) mice. There was no survival difference between KO and WT mice. There was also no difference in fibrosis between WT and KO mice, as determined by hydroxyproline content and collagen expression by real-time polymerase chain reaction (PCR). Within the bronchoalveolar lavage (BAL), the KO mice exhibited a significant increase in inflammatory cells, when compared to the WT mice (5.51 × 105 versus 2.35 × 105 cells/mL; P .001). Increased levels of the chemokine monocyte chemoattractant protein 1 (MCP-1) were observed in the lungs of the KO mice, confirmed via immunohistochemistry. In a subsequent in vitro experiment, MMP-13 was shown to cleave MCP-1. In ALI in the MMP-13 KO mice, MCP-1 could therefore remain active and potentially attract macrophages to the BAL. This study suggests a direct role for MMP-13 in modifying the inflammatory response in the lung after ALI.
AB - Human and animal studies of acute lung injury (ALI) have shown that matrix metalloproteinases (MMPs) play an important role in disease pathogenesis, but despite being detected during ALI, the function of the collagenase MMP-13 in ALI is unknown. To evaluate this role of MMP-13, mice deficient in MMP-13 (KO) were examined after hyperoxic lung injury, and compared to wild-type (WT) mice. There was no survival difference between KO and WT mice. There was also no difference in fibrosis between WT and KO mice, as determined by hydroxyproline content and collagen expression by real-time polymerase chain reaction (PCR). Within the bronchoalveolar lavage (BAL), the KO mice exhibited a significant increase in inflammatory cells, when compared to the WT mice (5.51 × 105 versus 2.35 × 105 cells/mL; P .001). Increased levels of the chemokine monocyte chemoattractant protein 1 (MCP-1) were observed in the lungs of the KO mice, confirmed via immunohistochemistry. In a subsequent in vitro experiment, MMP-13 was shown to cleave MCP-1. In ALI in the MMP-13 KO mice, MCP-1 could therefore remain active and potentially attract macrophages to the BAL. This study suggests a direct role for MMP-13 in modifying the inflammatory response in the lung after ALI.
KW - Acute lung injury
KW - Hyperoxia
KW - Knockout mice
KW - MCP-1
KW - MMP-13
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U2 - 10.3109/01902148.2010.497201
DO - 10.3109/01902148.2010.497201
M3 - Article
C2 - 20860538
AN - SCOPUS:78149263798
SN - 0190-2148
VL - 36
SP - 615
EP - 624
JO - Experimental Lung Research
JF - Experimental Lung Research
IS - 10
ER -
