A Comparative Analysis of In Vitro Toxicity of Synthetic Zeolites on IMR-90 Human Lung Fibroblast Cells

Broad industrial application of zeolites increases the opportunity of inhalation. However, the potential impact of different type and composition of zeolite on the cytotoxicity is still unknown. Four types of synthetic zeolites with have been prepared for assessing the effect on lung fibroblast: two zeolite L (LTL-R and LTL-D, ZSM-5 (MFI-S), and faujasite (FAU-S). The cytotoxicity of zeolites on human lung fibroblast (IMR-90) was assessed using WST1 cell proliferation assay, mitochondrial function, membrane leakage of lactate dehydrogenase, reduced glutathione levels, and mitochondrial membrane potential were assessed under control. Intracellular changes were examined using transmission electron microscopy (TEM). Toxicity related gene expression were evaluated by PCR array. The result showed a significantly higher toxicity in IMR-90 cells with FAU-S than LTL-R, LTL-D and MFI-S exposure. TEM showed FAU-S, spheroidal zeolite with a low Si/Al ratio, was readily internalized forming numerous phagosomes in IMR-90 cells, while the largest and disc-shaped zeolites showed the lowest toxicity and were located in submembranous phagosomes in IMR-90 cells. Differential expression of TNF related genes was detected using PCR arrays and confirmed using qRT-PCR analysis of selected genes. Collectively, the exposure of different zeolites shows different toxicity on IMR-90 cells.

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Effect of heparin and related glycosaminoglycan on PDGF-induced lung fibroblast proliferation, chemotactic response and matrix metalloproteinases activity

Mediators of Inflammation ◽

10.1080/096293500411541 ◽

2000 ◽

Vol 9 (2) ◽

pp. 85-91 ◽

Cited By ~ 16

Author(s):

Masahiro Sasaki ◽

Masayuki Kashima ◽

Takefumi Ito ◽

Akiko Watanabe ◽

Masaaki Sano ◽

...

Keyword(s):

Pulmonary Fibrosis ◽

Human Lung ◽

Heparan Sulphate ◽

Inhibitory Effect ◽

Lung Fibroblast ◽

Chemotactic Response ◽

Fibroblast Proliferation ◽

Human Lung Fibroblast ◽

Fibroblast Migration

Fibroblast migration, proliferation, extacellular matrix protein synthesis and degradation are the key events in various biological and pathological processes in pulmonary fibrosis. In addition, biopsy specimens from the lungs of patients with plumomary fibrosis show increased numbers of mast cells which have metachromatic granules containing heparin, histamin and proteases. Little is known about how these products influence pulmonary fibrosis. In the present study, we investigated the effect of heparin and related glycosaminoglycans on PDGF-induced lung fibroblast proliferation and chemotactic responsein vitro. In addition, we examined the effect of heparin on both the induction of matorix metalloproteinases (MMPs) and MMPs activity in lung fibroblastsin vitro.Heparin, de-N-sulphated heparin but not heparan sulphate inhibited PDGF-induced lung fibroblast proliferation. In contrast, only heparin inhibited PDGF-stimulated human lung fibroblast chemotaxis. Negatively charged poly-L-gultamic acid had no effect on either fibroblast proliferation or chemotaxis. Thus the negative charge alone cannot account for the ant-proliferative and anti-chemotactic effects of heparin.Furthermore, heparin and heparan sulphate also had no inhibitory effect on induction of MMPs, including MMP-1 (interstitial collagenase), MMP-2 (gelatinase A) and MMP-9 (gelatinase B). Only heparin inhibited both MMP-1 and MMP-2/MMP-9 activity. Additionally, tissue inhibitor of metalloproteinase type 1 (TIMP-1) and type 2 (TIMP-2) inhibited PDGF-stimulated human lung fibroblast chemotaxis. The ability of heparin to inhibit fibroblast chemotaxis may account for the inhibitory effect of heparin on MMP activity.The above results suggested that heparin and related glycosaminoglycans differentially regulate PDGF-induced lung fibroblast proliferation, chemotaxis and MMPs activity and further that these effects may have a key role in extracellular matrix remodeling in inflammatory lung disease.

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