Deficiency of matrix metalloproteinase-13 increases inflammation after acute lung injury

Anita I. Sen, Takayuki Shiomi, Yasunori Okada, Jeanine M. D'Armiento

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)615-624
Number of pages10
JournalExperimental Lung Research
Volume36
Issue number10
DOIs
Publication statusPublished - 2010 Nov

Fingerprint

Matrix Metalloproteinase 13
Acute Lung Injury
Inflammation
Chemokine CCL2
Bronchoalveolar Lavage
Macrophages
Polymerase chain reaction
Hydroxyproline
Collagenases
Lung
Matrix Metalloproteinases
Chemokines
Lung Injury
Animals
Collagen
Real-Time Polymerase Chain Reaction
Fibrosis
Immunohistochemistry
Survival
Experiments

Keywords

  • Acute lung injury
  • Hyperoxia
  • Knockout mice
  • MCP-1
  • MMP-13

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Deficiency of matrix metalloproteinase-13 increases inflammation after acute lung injury. / Sen, Anita I.; Shiomi, Takayuki; Okada, Yasunori; D'Armiento, Jeanine M.

In: Experimental Lung Research, Vol. 36, No. 10, 11.2010, p. 615-624.

Research output: Contribution to journalArticle

Sen, Anita I. ; Shiomi, Takayuki ; Okada, Yasunori ; D'Armiento, Jeanine M. / Deficiency of matrix metalloproteinase-13 increases inflammation after acute lung injury. In: Experimental Lung Research. 2010 ; Vol. 36, No. 10. pp. 615-624.
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