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PubMed1996

Micronucleus formation in V79 cells treated with respirable silica dispersed in medium and in simulated pulmonary surfactant.

Chinese hamster lung fibroblasts (V79 cells) were challenged with respirable silica particles using an in vitro genotoxicity assay. Two particle sizes of crystalline quartz and a non-crystalline silica were assayed for induction of micronuclei (MN) in V79 cells. Some of the silica dusts used were pretreated with simulated pulmonary surfactant to model in vivo exposure conditions. The results showed that both crystalline and non-crystalline silica dispersed in medium (MEM) induced MN formation in a dose-dependent manner. Crystalline silica was more active in this assay than non-crystalline silica on a mass basis. The results also show that the frequency of micronucleated cells in cultures treated with surfactant-coated silica was not significantly different from that of the non-treated control cultures. These results seem to indicate that silica can cause chromosomal aberrations and/or aneuploidies in V79 cells; however, pretreatment of silica particles with simulated pulmonary surfactant reduces or delays genotoxicity in this assay.

Animals↗
PubMed2000

Enhancement of nuclear factor-kappaB activation and protein tyrosine phosphorylation by a tyrosine phosphatase inhibitor, pervanadate, involves reactive oxygen species in silica-stimulated macrophages.

Reactive oxygen species (ROS) and phosphorylation events mediated by tyrosine kinase are involved in silica-induced nuclear factor-kappa B (NF-kappaB) activation. Protein tyrosine phosphatase (PTPase) acts to limit protein tyrosine phosphorylation. In the present study, we investigated the role of PTPase in NF-kappaB activation and tyrosine phosphorylation in silica-stimulated macrophages, and the involvement of ROS in these responses. Treatment of mouse peritoneal macrophages (RAW264.7 cells) with a PTPase inhibitor, pervanadate, markedly enhanced the DNA-binding activity of NF-kappaB in the presence or absence of silica. The stimulatory effect of pervanadate on NF-kappaB activation was also demonstrated in LPS-stimulated macrophages. A specific inhibitor of protein tyrosine kinase (PTK), genistein, prevented the NF-kappaB activation induced by pervanadate in the presence of silica while inhibitors of protein kinase A or C, such as staurosporine or H7, had no inhibitory effect on NF-kappaB activation. A variety of antioxidants, such as catalase, superoxide dismutase, N-acetyl cysteine (NAC), and pyrrolidine dithiocarbamate, inhibited NF-kappaB activation induced by pervanadate in the presence of silica. Furthermore, pervanadate markedly enhanced silica- or LPS-induced protein tyrosine phosphorylation in cells. Treatment of macrophages with NAC abolished the increase in tyrosine phosphorylation in cells stimulated with the combination of pervanadate and either silica or LPS or with silica alone. The results suggest that PTPase may play a crucial role in the negative regulation of silica-signaling pathways leading to NF-kappaB activation in macrophages. Furthermore, ROS appear to be involved in downstream signaling between PTPase inhibition and NF-kappaB activation.

Animals↗
PubMed2000

Cytotoxic and transforming effects of silica particles with different surface properties in Syrian hamster embryo (SHE) cells.

Several crystalline and amorphous silica dusts (two quartz of natural origin, one cristobalite of natural and two of biogenic origin, three amorphous diatomite earths and one pyrogenic amorphous silica) were studied in the SHE cell transformation assay, in order to compare their cytotoxic and transforming potencies and examine the role of the structure and of the state of the surface on these effects. Some samples were modified by grinding, etching and heating with the aim of establishing relationships between single surface properties and biological responses. The results showed that some quartz and cristobalite dusts (crystalline) as well as the diatomaceous earths (amorphous), but not the pyrogenic amorphous silica, were cytotoxic and induced morphological transformation of SHE cells in a concentration-dependent manner. The ranking in cytotoxicity was different from that in transforming potency, suggesting two separate molecular mechanisms for the two effects. The cytotoxic and transforming potencies were different from one dust to another, even among the same structural silicas. The type of crystalline structure (quartz vs cristobalite) and the crystalline vs biogenic amorphous form did not correlate with cytotoxic or transforming potency of silica dusts. Comparison of cellular effects induced by original and surface modified samples revealed that several surface functionalities modulate cytotoxic and transforming potencies. The cytotoxic effects appeared to be related to the distribution and abundance of silanol groups and to the presence of trace amounts of iron on the silica surface. Silica particles with fractured surfaces and/or iron-active sites, able to generate reactive oxygen species, induced SHE cell transformation. The results show that the activity of silica at the cellular level is sensitive to the composition and structure of surface functionalities and confirm that the biological response to silica is a surface originated phenomenon.

Animals↗
PubMed2007

Size control of silica nanoparticles and their surface treatment for fabrication of dental nanocomposites.

Nearly monodispersed silica nanoparticles having a controlled size from 5 to 450 nm were synthesized via a sol-gel process, and then the optimum conditions for the surface treatment of the synthesized silica nanoparticles with a silane coupling agent (i.e., 3-methacryloxypropyltrimethoxysilane (gamma-MPS)) were explored to produce dental composites exhibiting enhanced adhesion and dispersion of silica nanoparticles in the resin matrix. The particle size was increased by increasing amounts of the catalyst (NH4OH) and silica precursor (tetraethylorthosilicate, TEOS) and by decreasing the amount of water in the reaction mixtures regardless of solvents used for the synthesis. The particle size prepared by using ethanol as a solvent was significantly larger than that prepared by using methanol as a solvent when the composition of the reaction mixture was fixed. The nanosized particles in the 5-25 nm range were aggregated. The amount of grafted gamma-MPS on the surface of the synthesized silica nanoparticles was dependent on the composition of the reaction mixture when an excess amount of gamma-MPS was used. When surface treatment was performed at optimum conditions found here, the amount of the grafted gamma-MPS per unit surface area of the silica nanoparticles was nearly the same regardless of the particle size. Dispersion of the silica particles in the resin matrix and interfacial adhesion between silica particles and resin matrix were enhanced when surface treated silica nanoparticles were used for preparing dental nanocomposites.

Dental Materials↗
PubMed2005

Controlled polymerization in mesoporous silica toward the design of organic-inorganic composite nanoporous materials.

Free-radical polymerization inside mesoporous silica has been investigated in order to open a route to functional polymer-silica composite materials with well-defined mesoporosity. Various vinyl monomers, such as styrene, chloromethyl styrene, 2-hydroxyethyl methacrylate, and methacrylic acid, were polymerized after impregnation into mesoporous silicas with various structures, which were synthesized using polyalkylene oxide-type block copolymers. The location of the polymers was systematically controlled with detailed structures of the silica framework and the polymerization conditions. Particularly noteworthy is the polymer-silica composite structure obtained by in situ polymerization after the selective adsorption of monomers as a uniform film on silica walls. The analysis of XRD data and the N(2) adsorption isotherms indicates the formation of uniform polymer nanocoating. The resultant polymer-silica composite materials can easily be post-functionalized to incorporate diverse functional groups in high density, due to the open porous structure allowing facile access for the chemical reagent. The fundamental characteristics of the composite materials are substantiated by testing the biomolecule's adsorption capacity and catalytic reactivity. Depending on the structure and composition of polymers, the resultant polymer-silica composite materials exhibit notably distinct adsorption properties toward biomolecules, such as proteins. Furthermore, it is demonstrated that the nanocoatings of polymers deposited on the mesopore walls have remarkably enhanced catalytic activity and selectivity, as compared to that of bulk polymer resins. We believe that, due to facile functionalization and attractive textural properties, the mesoporous polymer-silica composite materials are very useful for applications, such as adsorption, separation, host-guest complexes, and catalysis.

Journal Article↗
PubMed2005

Vesicle array-templated large-area silica surface patterns.

Micropatterning has important applications in a wide range of areas, including microelectronics, optics, information displays, and biotechnology. Herein, we describe a vesicle-array templating approach for the generation of surface patterns of micrometer-sized silica features on the surfaces of silica monoliths. The approach makes use of tetraethyl orthosilicate as silica precursor, a poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) triblock copolymer, EO2PO16EO2, as surfactants, and water, ethanol, and dimethylformamide as solvents. The morphological shapes of produced silica features are synthetically controlled through varying the sequence of silica precursor hydrolysis, vesicle formation, and silica condensation. Prehydrolysis of the silica precursor, before being mixed with the copolymer, gives hollow convex protrusions. Direct mixing of the silica precursor and the copolymer produces concave depressions. An increase in the amount of water in the mixture solution without prehydrolysis of the silica precursor results in hierarchical patterns of larger concave depressions attached with smaller convex protrusions. It has further been demonstrated that concave surface patterns can function as microlens arrays that are capable of producing numerous optical images from a common object.

Journal Article↗
PubMed2005

Facile synthesis of mesoporous silica sublayer with hierarchical pore structure on ceramic membrane using anionic polyelectrolyte.

A facile method for introducing mesoporous silica sublayer onto the surface of a ceramic membrane for use in liquid-phase separation is described. To reduce the electrostatic repulsion between the mesoporous silica sol and the ceramic membrane in highly acidic conditions (pH < 2), thus facilitating the approach of hydrolyzed silica sol to the surface of the membrane, poly(sodium 4-styrenesulfonate) (Na+PSS-, denoted as PSS-) was used as an ionic linker. The use of PSS- led to a significant reduction in positive charge on the ceramic membrane, as confirmed by experimental titration data. Consistent with the titration results, the amount of mesoporous silica particles on the surface of the ceramic membrane was low, in the absence of PSS- treatment, whereas mesoporous silica sublayer with hierarchical pore structure was produced, when 1 wt % PSS- was used. The results show that mesoporous silica grows in the confined surface, eventually forming a multistacked surface architecture. The mesoporous silica sublayer contained uniform, ordered (P6 mm) mesopores of ca. 7.5 nm from mesoporous silica as well as macropores ( approximately mum) from interparticle voids, as evidenced by transmission electron microscopy and scanning electron microscopy analyses. The morphologies of the supported mesoporous silica could be manipulated, thus permitting the generation of uniform needlelike forms or uniform spheroid particles by varying the concentration of PSS-.

Journal Article↗
PubMed2006

Polystyrene-silica nanocomposite particles via alcoholic dispersion polymerization using a cationic azo initiator.

Submicrometer-sized polystyrene-silica nanocomposite particles have been prepared by alcoholic dispersion polymerization of styrene using commercial alcoholic silica sols of 13 or 22 nm diameter as the sole stabilizing agent. The key to the formation of colloidally stable nanocomposite particles is the selection of a cationic azo initiator (use of nonionic or anionic initiators leads either to the formation of silica-stabilized polystyrene latex particles with very low silica contents or to the precipitation of polystyrene, respectively). Neither surface modification of the silica sol nor the addition of surfactant or polymeric stabilizers is required for successful nanocomposite syntheses. The purified polystyrene-silica nanocomposite particles have relatively narrow particle size distributions, with mean diameters ranging from 331 to 464 nm as judged by disk centrifuge photosedimentometry. Thermogravimetric analyses indicated mean silica contents of 13-26 wt. %, depending on the synthesis conditions. Calcination of the polystyrene-silica nanocomposite particles leads to the formation of hollow silica shells, which indicates a well-defined core-shell morphology for the original nanocomposite particles.

Journal Article↗
PubMed1998

Evaluation of the osteoblast response to a silica gel in vitro.

Many bioactive glasses and glass ceramics contain silica, yet the effect of silica on the osteoblast is not well understood. The osteoblast cell response to a silica surface, without the interference of the other ions present in glasses and glass ceramics has been investigated. A silica sol-gel was prepared which gave a molar ratio of 1:4:4 tetraethyl orthosilicate (TEOS): ethanol:acidified water 0.2 M HCl) and spin cast on to thermanox discs. The gel was characterized in terms of bioactivity and release of silicic acid. Primary human osteoblasts (HOBs) were seeded on the surface of upright or inverted silica discs. Cell activity (alamar blue reduction), number (DNA content) and differentiation (alkaline phosphatase activity, nodule formation and mineralization) were measured. There was no apparant difference in cell number, activity or alkaline phosphatase activity between silica discs and controls. Nodules formed much earlier on the silica surfaces and these eventually mineralized. Nodule formation was reproducibly enhanced on the silica surface and less markedly on the inverted discs. It is likely that both the surface characteristics of the silica gel and silicic acid release from the disc affect osteoblast behaviour.

Journal Article↗
PubMed2005

Preparation of 2-mercaptobenzothiazole-derivatized mesoporous silica and removal of Hg(ii) from aqueous solution.

Mesoporous silicas (SBA-15 and MCM-41) have been functionalized by two different methods. Using the heterogeneous route the silylating agent, 3-chloropropyltriethoxysilane, was initially immobilized onto the mesoporous silica surface to give the chlorinated mesoporous silica Cl-SBA-15 or Cl-MCM-41. In a second reaction a multifunctionalized N,S donor compound (2-mercaptobenzothiazol) was incorporated to obtain the functionalized silicas denoted as MBT-SBA-15-Het and MBT-MCM-41-Het. Using the homogeneous route, the functionalization was achieved via the one step reaction of the mesoporous silica with an organic ligand containing the chelating functions, to give the modified mesoporous silicas denoted as MBT-SBA-15-Hom or MBT-MCM-41-Hom. The functionalized mesoporous silicas were employed as adsorbents for the regeneration of aqueous solutions at pH 6 contaminated with Hg(ii) at room temperature. Results obtained indicate that mercury adsorption was higher in the mesoporus silicas prepared by the homogeneous method, and the maximum adsorption value (0.24 +/- 0.02 mmol Hg(ii) g(-1)) was obtained for MBT-SBA-15-Hom. The chemically stability in acid medium of the functionalized silicas, possibility its regeneration washing with concentrate HCl, resulting in the reuse of the adsorbent material for several cycles.

Adsorption↗
PubMedDate not supplied

Lung dust content and response in guinea pigs inhaling three forms of silica.

Guinea pigs were exposed by inhalation to atmospheric suspensions of crystalline free silica (cristobalite), amorphous free silica (diatomaceous earth), and amorphous silicate (volcanic glass). Randomly selected animals were killed at 2-month intervals and their lungs were examined. Tissue samples were collected and analyzed for total silica content and total ash. Total silica content per lung increased linearly throughout at least 21 months in each experiment and total ash weight increased more rapidly than dust was accumulating. Crystalline silica produced a greater increment in ash weight that did the amorphous free silica and the silicate produced the least increase. Furthermore, although atmospheric dust concentrations were roughly comparable for the three preparations, the total amount of silica accumulated varied inversely with the degree of tissue damage occurring. Thus, the maximum total content of the crystalline silica reached only 68 mg per lung, while that of the amorphous silica and silicate was 120 mg and 465 mg, respectively. This suggests that a silicious dust that produces cell damage may be cleared more effectively from the lung than is an innocuous dust.

Animals↗
PubMed1996

Pulmonary microsomal metabolism of benzo[a]pyrene following exposure of rats to silica.

Because some evidence suggests that there may be an increased incidence of lung cancer in silicosis and because previous studies have shown that exposure of rats to silica alters the pulmonary cytochrome P-450 system, we studied the effects of exposing rats to silica on the lung microsomal metabolism of benzo[a]pyrene (BaP). Rats were exposed to silica by intratracheal administration, lung microsomes were obtained 2 wk later from untreated and silica-treated animals, and the amounts of microsomal tissue and metabolites formed during the in vitro microsomal metabolism of BaP were measured. When the formation of BaP metabolites in equal amounts of lung microsomal tissue from the 2 treatment groups is compared, 3-OH BaP, BaP 4,5-diol, and BaP 9,10-diol are reduced by 45-70%, but the formation of BaP 7,8-diol or the BaP-quinones is not significantly altered following exposure to silica. In fact, the ratio of the BaP diols and BaP quinones, potentially toxic metabolites, to the relatively nontoxic 3-OH BaP produced by equal amounts of lung microsomal tissue is increased more than threefold following exposure of rats to silica. Since exposure of rats to silica leads to increased levels of lung microsomal protein, the amounts of BaP metabolites that could be produced by all microsomal tissue in the lungs were calculated. In silica-treated animals, the calculated total lung production of 3-OH BaP, BaP 4,5-diol, and BaP 9,10-diol tends to be increased by 1.2- to 2.0-fold, but BaP 7,8-diol and the BaP quinones are increased by 3.5-fold. These results demonstrate that exposure of rats to silica may alter the capacity of the lungs to metabolize benzo[a]pyrene, and the greatest effect seems to be enhanced accumulation of BaP 7,8-diol and the BaP quinones.

Animals↗
PubMed2000

Subchronic silica exposure enhances respiratory defense mechanisms and the pulmonary clearance of Listeria monocytogenes in rats.

Both Listeria monocytogenes infection and silica exposure have been shown to significantly alter immune responses. In this study, we evaluated the effect of preexposure to silica on lung defense mechanisms using a rat pulmonary L. monocytogenes infection model. Male Sprague-Dawley rats were instilled intratracheally with saline (vehicle control) or silica using either an acute treatment regimen (5 mg/kg; 3 days) or a subchronic treatment protocol (80 mg/kg; 35 days). At 3 or 35 days after silica instillation, the rats were inoculated intratracheally with either approximately 5000 or 500,000 L. monocytogenes. At 3, 5, and 7 days postinfection, the left lung was removed, homogenized, and cultured on brain heart infusion agar at 37 degrees C. The numbers of viable L. monocytogenes were counted after an overnight incubation. Bronchoalveolar lavage (BAL) was performed on the right lungs, and BAL cell differentials, acellular lactate dehydrogenase (LDH) activity and albumin content were determined. Alveolar macrophage (AM) chemiluminescence (CL) and phagocytosis were assessed as a measure of macrophage function. Lung-associated lymph nodes were removed, and lymphocytes were recovered and differentiated. Preexposure to silica significantly increased the pulmonary clearance of L. monocytogenes as compared to saline controls. Exposure to silica caused significant increases in BAL neutrophils, LDH and albumin, and lymph-nodal T cells and natural killer (NK) cells in infected and noninfected rats. CL and phagocytosis were also elevated in silica-treated rats. In summary, the results demonstrated that exposure of rats to silica enhanced pulmonary immune responses, as evidenced by increases in neutrophils, NK cells, T lymphocytes, and macrophage activation. These elevations in pulmonary immune response are likely responsible for the increase in pulmonary clearance of L. monocytogenes observed with preexposure to silica.

Animals↗
PubMed2004

Immunoglobulin and lymphocyte responses following silica exposure in New Zealand mixed mice.

Epidemiological studies have shown strong associations between silica exposure and several autoimmune diseases, including scleroderma and systemic lupus erythematosus. We previously reported that the New Zealand mixed (NZM) mouse develops silicosis and exacerbated autoimmunity following crystalline silica exposure, including increased levels of autoantibodies, proteinuria, circulating immune complexes, pulmonary fibrosis, and glomerulonephritis. In this study, the NZM mouse was used to examine changes in immune activation following silica exposure by measuring levels of immunoglobulin, cytokines and lymphocyte populations. Levels of immunoglobulin (Ig) G1 were significantly decreased from 1124 +/- 244 microg/ml in saline exposed mice to 614 +/- 204 microg/ml in silica-exposed mice, suggesting a decrease in the Th2 response. The levels of tumor necrosis factor (TNF)-alpha were significantly increased (1.5-fold) in the bronchoalveolar lavage fluid of the silica-exposed mice as compared to the saline-exposed mice. The number of B1a B cells were significantly increased sixfold within the superficial cervical lymph nodes of silica-exposed mice as compared with saline-exposed mice. Following silica exposure, CD4+ T cells significantly increased threefold within the superficial cervical lymph nodes. During this increase in the number of CD4+ T cells, the number of CD4+CD25+ regulatory T cells was not significantly changed, altering the ratio of regulatory T cells to T helper cells from 1:5 to 1:8 following silica exposure. Therefore, the silica-induced alterations in immunoglobulin levels, increased TNF-alpha, increased B1a B cells and CD4+ T cells, with decreased regulatory T cells, may provide an environment that allows for increased autoreactivity. These studies begin to provide possible mechanisms for environmentally induced autoimmune diseases that have been reported in many epidemiological studies.

Animals↗
PubMedDate not supplied

Reactive oxygen species and silica-induced carcinogenesis.

Although silica has recently been designated as a carcinogen, its mechanism of carcinogenesis is not fully understood. Recent studies suggest that free-radical reactions may play an important role in the initiation and progression of cancer. This article summarizes literature on the generation of reactive oxygen species (ROS) directly from silica and from silica-stimulated cells. It also summarizes information concerning the role of ROS in silica-induced DNA damage as well as in silica-induced cell proliferation, including the effects of silica on the activation of nuclear transcription factors, induction of growth factors and oncogene expression, redox regulation of the p53 tumor suppressor gene, induction of apoptosis, and division of damaged cells. Understanding the role of ROS in silica-mediated reactions may help develop therapeutic agents to block silica-induced free radical reactions and thus prevent or attenuate silica-induced carcinogenesis.

Animals↗
PubMed1980

Dissociation of intracellular lysosomal rupture from the cell death caused by silica.

The relationship between intracellular lysosomal rupture and cell death caused by silica was studied in P388d(1) macrophages. After 3 h of exposure to 150 mug silica in medium containing 1.8 mM Ca(2+), 60 percent of the cells were unable to exclude trypan blue. In the absence of extracellular Ca(2+), however, all of the cells remained viable. Phagocytosis of silica particles occurred to the same extent in the presence or absence of Ca(2+). The percentage of P388D(1) cells killed by silica depended on the dose and the concentration of Ca(2+) in the medium. Intracellular lyosomal rupture after exposure to silica was measured by acridine orange fluorescence or histochemical assay of horseradish peroxidase. With either assay, 60 percent of the cells exposed to 150 mug silica for 3 h in the presence of Ca(2+) showed intracellular lysosomal rupture, was not associated with measureable degradation of total DNA, RNA, protein, or phospholipids or accelerated turnover of exogenous horseradish peroxidase. Pretreatment with promethazine (20 mug/ml) protected 80 percent of P388D(1) macrophages against silica toxicity although lysosomal rupture occurred in 60-70 percent of the cells. Intracellular lysosomal rupture was prevented in 80 percent of the cells by pretreatment with indomethacin (5 x 10(-5)M), yet 40-50 percent of the cells died after 3 h of exposure to 150 mug silica in 1.8 mM extracellular Ca(2+). The calcium ionophore A23187 also caused intracellular lysosomal rupture in 90-98 percent of the cells treated for 1 h in either the presence or absence of extracellular Ca(2+). With the addition of 1.8 mM Ca(2+), 80 percent of the cells was killed after 3 h, whereas all of the cells remained viable in the absence of Ca(2+). These experiments suggest that intracellular lysosomal rupture is not causally related to the cell death cause by silica or A23187. Cell death is dependent on extracellular Ca(2+) and may be mediated by an influx of these ions across the plasma membrane permeability barrier damaged directly by exposure to these toxins.

Animals↗
PubMed1996

Function of silica bodies in the epidermal system of rice (Oryza sativa L.): testing the window hypothesis.

Silicon has been considered to be important for normal growth and development of the rice plant (Oryza sativa L.). To investigate the physiological function of deposited silica in rice leaves, the hypothesis that silica bodies in the leaf epidermal system might act as a 'window' to facilitate the transmission of light to photosynthetic mesophyll tissue was tested. The silica content of leaves increased with supplied silicon and was closely correlated with the number of silica bodies per unit leaf area in the epidermal system. There was a significant difference in silica deposition and formation of silica bodies between Si-treated and non-treated leaves; silicon was polymerized inside the silica cells and bulliform cells of the epidermis, in Si-treated leaves. Although the 'windows' were only formed in leaves with applied silicon, optical properties of leaf transmittance, reflectance and absorptance spectra in Si-treated and non-treated leaves were almost equal. Furthermore, light energy use efficiency and quantum yield of Si-treated leaves were less than in leaves not containing silica bodies. Thus, silica bodies, at least based on the data, do not function as windows in rice leaves.

Carbon Dioxide↗
PubMed2004

p38 and Src-ERK1/2 pathways regulate crystalline silica-induced chemokine release in pulmonary epithelial cells.

Crystalline silica has been shown to trigger pulmonary inflammation both in vivo and in vitro, but the underlying molecular mechanisms remain unclear. In the present study we focus on the intracellular signaling pathways regulating chemokine release from lung epithelial cells after crystalline silica exposure. Our results show that silica particles induced a concentration- and time-dependent increase in interleukin (IL)-8 release from the human epithelial lung cell line A549. The IL-8 induction was significantly attenuated by inhibitors of the mitogen-activated protein kinases (MAPKs), p38 (SB202190) and extracellular signal-regulated kinase (ERK)-1 and -2 (PD98059), as well as a general protein tyrosine kinase (PTK) inhibitor (genistein). However, IL-8 induction was most efficiently inhibited by the Src family kinase (SFK) inhibitor, PP2, suggesting a crucial role of SFKs in regulating silica-induced IL-8 release from A549 cells. Silica exposure induced phosphorylation of the MAPKs p38 and ERK1/2, but not JNK or ERK5. Silica also induced a significant phosphorylation of SFKs. Moreover, PP2 inhibited silica-induced phospho-ERK1/2 to near-control levels, whereas phospho-p38 was not significantly reduced by the SFK inhibitor. Our results suggest the presence of two separate signaling pathways which are important in the regulation of silica-induced IL-8 release from A549 cells; one involving SFK-dependent activation of ERK1/2, and the other activation of p38, at least partly independent of SFKs. Experiments with primary type 2 (T2) cells from rat lungs suggest that crystalline silica-induced release of macrophage inflammatory protein (MIP)-2 is regulated through similar mechanisms.

Animals↗