Ionizing radiation enhances matrix metalloproteinase-2 production in human lung epithelial cells

Abstract

Radiation pneumonitis is a major complication of radiation therapy. However, the detailed cellular mechanisms have not been clearly defined. Based on the recognition that basement membrane disruption occurs in acute lung injury and that matrix metalloproteinase (MMP)-2 can degrade type IV collagen, one of the major components of the basement membrane, we hypothesized that ionizing radiation would modulate MMP-2 production in human lung epithelial cells. To evaluate this, the modulation of MMP-2 with irradiation was investigated in normal human bronchial epithelial cells as well as in A549 cells. We measured the activity of MMP-2 in the conditioned medium with zymography and the MMP-2 mRNA level with RT-PCR. Both of these cells constitutively expressed 72-kDa gelatinolytic activity, corresponding to MMP-2, and exposure to radiation increased this activity. Consistent with the data of zymography, ionizing radiation increased the level of MMP-2 mRNA. This radiation-induced increase in MMP-2 expression was mediated via p53 because the p53 antisense oligonucleotide abolished the increase in MMP-2 activity as well as the accumulation of p53 after irradiation in A549 cells. These results indicate that MMP-2 expression by human lung epithelial cells is involved in radiation-induced lung injury.

Ionizing Radiation Enhances Matrix Metalloproteinase-2 Secretion and Invasion of Glioma Cells through Src/Epidermal Growth Factor Receptor–Mediated p38/Akt and Phosphatidylinositol 3-Kinase/Akt Signaling Pathways

“…Transforming growth factor-h (39), laminin, an ECM component (40), interleukin-8 (41), and insulin like growth factor-1 (42) have all been shown to alter the expression or function of MMP-2. In addition, IR potently induces MMP-2 in various normal cells (43)(44)(45) and was also found to induce invasion and metastasis in several types of cancer cells in vitro and in vivo, including gliomas (28-31). Here, we found that IR potently induced MMP-2 expression and invasion in various glioma cells.…”

Radiation‐induced gene expression profile of human cells deficient in 8‐hydroxy‐2′‐deoxyguanine glycosylase

“…Ionizing radiation enhances MMP-2 production. 46 It has been suggested that ionizing radiation might affect the process of angiogenesis through a direct effect on the extracellular matrix and specifically on collagen type IV. 47 Type V collagen, another gene found to be upregulated (Fig.…”

Modulation of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in RAW264.7 cells by irradiation

“…Since macrophages produce numerous bioactive substances (2), rubin et al (3) proposed that the inflammatory process involves an interplay of cellular interactions, a perpetual cascade of cytokines involved in radiation-induced pulmonary injury, including tumor necrosis factor-α (TnF-α), interleukin-1β (il-1β), interleukin-6 (IL-6) and tumor growth factor-β (TGF-β). it has been suggested that the disruption and alteration of the basement membrane plays a role in radiation-induced pulmonary injury (4). Matrix metalloproteinases (MMPs) are a large family of related proteolytic enzymes (5).…”

“…However, human alveolar macrophages have been shown to release il-1 within hours of irradiation in vitro (11), and low-dose irradiation to induce IL-1 and IL-6 expression in mouse macrophages in vitro (12). araya et al (4) found that ionizing radiation enhanced the expression of MMP-2 in human lung epithelial cells in vitro, suggesting that MMP-2 is involved in radiation-induced lung injury. However, whether ionizing radiation stimulates macrophage cells in vitro to produce MMP-9 has yet to be determined.…”