Stromelysin-2 (MMP-10) facilitates clearance and moderates inflammation and cell death following lung exposure to long multiwalled carbon nanotubes

Abstract

Multiwalled carbon nanotubes (MWCNTs) are nanomaterials composed of multiple layers of graphene cylinders with unique properties that make them valuable for a number of industries. However, rising global production has led to concerns regarding potential occupational exposures to them as raw materials during handling. This is especially true for long MWCNT fibers, whose aspect ratio has been posited to initiate pathology similar to that of asbestos. Matrix metalloproteinases (MMPs) are a class of extracellular endopeptidases that control various processes related to tissue repair, inflammation, and more. Stromelysin-2 (MMP-10) has roles in modulating macrophage activation and function, and hence, we used an MMP-10 null ( Mmp10 −/− ) mouse model to assess its role in controlling lung responses to inhaled long MWCNTs. Oropharyngeal aspiration of long MWCNTs (80 µg/mouse) by wild-type mice induced expression of Mmp10 mRNA, which was accompanied by a robust inflammatory response characterized by elevated expression of Tnfa , Il6 , and Il1b . In Mmp10 −/− mice, we found that absence of MMP-10 led to impaired pulmonary clearance of MWCNTs and reduced macrophage cell survival. Exposure of wild-type bone marrow-derived macrophages (BMDMs) and alveolar macrophages to MWCNTs caused a rapid, dose-dependent upregulation of Mmp10 mRNA expression, which was accompanied by expression of pro-inflammatory products ( Il6 and Il1b ). These products were further enhanced in Mmp10 −/− macrophages, resulting in increased caspase-3-dependent cell death compared with wild-type cells. These findings indicate that MMP-10 facilitates the clearance of MWCNTs and moderates the pro-inflammatory response of exposed alveolar and infiltrated macrophages.

Engineering of tissue inhibitor of metalloproteinases TIMP-1 for fine discrimination between closely related stromelysins MMP-3 and MMP-10

“…In the inflammatory setting triggered by acute infection, MMP-10 produced by macrophages moderates inflammation and protects against tissue damage (41,48,49). Similar protective effects are seen in lung injury caused by inhalation of long multiwalled carbon nanotubes (50). Studies of MMP-9 in lung disease have shown context-dependent profibrotic and anti-fibrotic effects in different models of lung fibrosis (51).…”

Inflammation biomarker discovery in Parkinson’s disease and atypical parkinsonisms

“…MMP-10 is a secreted metalloproteinase with a key role on modulation of macrophage activation and function. MMP-10 is not expressed in unchallenged tissues, but is increased in response to a variety of insults [44]. Thus, a positive correlation of MMP-10 CSF levels with disease progression might indicate increased inflammation and neuronal loss.…”

MMP10 involved in Radiosensitivity in Non-Small Cell Lung Cancer via DNA damage repair pathway

“…MMP10 participates in many physiological and pathological processes, and plays an important role in embryonic development, tissue damage repair and other processes [26]. Recent research shows that MMP10 plays a signi cantly important role in the activation of pro MMPs [27]; MMP10 is highly expressed in epithelial tumors such as gastric cancer, bladder transitional cell cancer, esophageal cancer, skin cancer and non-small cell lung cancer [17,[28][29][30]. In our study, we found that knockdown MMP10 in A549 cells by MMP10 siRNA could signi cantly inhibit the proliferation and promoted apoptosis after IR.…”