Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The manner in which wear debris initiates intracellular signaling and macrophage activation remains poorly understood. While particle phagocytosis has been implicated in this process, recent studies have shown that phagocytosis is not required for macrophage activation. We examined the hypothesis that titanium particles stimulate macrophages through membrane associated signaling events involving free radicals, sphingomyelinase, NFkappaB, and TNFalpha. Titanium particles stimulated peroxidation of linoleic acid, producing malondialdehyde, while neither lipopolysaccharide nor PBS pre-incubated with particles did, suggesting that the increased peroxidation is related to the presence of the particles themselves. Furthermore, particles stimulated sphingomyelin metabolism in a neutral sphingomyelinase (NSmase) containing cell free system; this effect was inhibited by glutathione, indicating that NSmase activation was due to titanium induced free radicals. Titanium particles also stimulated NSmase activity in cultures of ANA-1 murine macrophages. Addition of purified NSmase to ANA-1 cell cultures stimulated NFkappaB binding, increased transcriptional activity in cells transfected with NFkappaB responsive promoters, and induced TNFalpha expression. These effects were also inhibited by addition of glutathione. Similarly, glutathione inhibited the ability of titanium particles to induce NFkappaB signaling and TNFalpha expression in ANA-1 cells. The findings demonstrate that titanium particles generate free radicals and induce plasma membrane peroxidation and NSmase activation. NSmase, in turn, hydrolyzes sphingomyelin, with activation of the NFkappaB signaling pathway and induction of responsive genes, including TNFalpha. This study demonstrates a mechanism for phagocytosis-independent macrophage activation and defines the sphingomyelin cycle as a potential therapeutic target for the prevention of wear debris induced osteolysis.
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PMID:Sphingomyelinase mediates macrophage activation by titanium particles independent of phagocytosis: a role for free radicals, NFkappaB, and TNFalpha. 1594 9

Particulates in air pollution have been strongly associated with asthma symptoms. These particulates are a conglomeration of many components, including metals, polyaromatic hydrocarbons, and lipopolysaccharide, that may cause oxidative stress upon uptake by alveolar macrophages. The objective of this study was to assess whether uptake of a model air particulate (SRM 1648) causes oxidative stress in macrophages resulting in the production of the eicosanoid mediator prostaglandin E(2) (PGE(2)) that might exacerbate asthma. SRM 1648 suspended in phosphate-buffered saline (PBS) was introduced into wells with plated RAW 264.7 monocyte/macrophages. Following incubation of SRM 1648 with RAW 264.7 macrophages, prostaglandin E(2) was measured by enzyme immunosorbent assay (EIA), and oxidative stress was assessed by the levels of intracellular reduced glutathione (GSH) as well as by the oxidation of dihydrodichlorofluorescein (H(2)DCFDA) to the fluorescent dichlorofluoresecein (DCF). The results indicated that SRM 1648 caused oxidative stress in RAW 264.7 macrophages, as shown by a compensatory increase in GSH levels in comparison to the controls of titanium dioxide and media alone. Prostaglandin E(2) levels significantly increased at the 3-, 6-, and 12-h time points. Introduction of GSH ester to buffer against oxidative stress was able to block the elevation of PGE(2). The data show that SRM 1648 causes oxidative stress in RAW 264.7 macrophages resulting in formation of the potential Th2 mediator prostaglandin E(2).
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PMID:Air pollution particulate SRM 1648 causes oxidative stress in RAW 264.7 macrophages leading to production of prostaglandin E2, a potential Th2 mediator. 1628 64

Fine particles (10(2)- to 10(3)-nm diameter) are potentially potent adjuvants in acquired immune responses but little is known about their interaction with pathogen-associated molecular patterns (PAMPs) and impact upon innate immunity. Here we show that 200-nm-sized, food-grade titanium dioxide avidly binds lipopolysaccharide (LPS) with bridging calcium cations, and the complex induces marked proinflammatory signalling in primary human mononuclear phagocytes. In particular, caspase 1-dependent interleukin-1beta (IL-1beta) secretion was induced at levels far greater than for the sum of the individual components, and without concomitant secretion of modulatory cytokines such as interleukin-1 receptor antagonist or transforming growth factor-beta1 (TGF-beta1). Secondly, the conjugate induced apoptotic-like cell death. These responses were inhibited by blockade of both phagocytosis and scavenger receptor uptake. Specific caspase 1-facilitated IL-1beta secretion and apoptosis following phagocytosis are features of cellular responses to certain invasive, enteric pathogens, and hence induction of these events may be mimicked by fine particle-LPS conjugates. The inadvertent adsorption of PAMPs to ingested, inhaled, or "wear" fine particulate matter provides a further potential mechanism for the proinflammatory nature of fine particles.
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PMID:Fine particles that adsorb lipopolysaccharide via bridging calcium cations may mimic bacterial pathogenicity towards cells. 1720 80

Tumor necrosis factor alpha (TNFalpha) plays a fundamental role in the pathogenesis of wear particle-induced periprosthetic osteolysis. However, particle-induced mechanisms that control TNFalpha gene expression are not yet well characterized. LITAF [lipopolysaccharide (LPS)-induced TNFalpha factor] is a novel transcription factor that regulates expression of the TNFalpha gene, but nothing is known about its role in wear particle-induced osteolysis. We evaluated the effect of titanium aluminum vanadium (TiAlV) and polyethylene particles on mRNA expression of LITAF. A human monocytic leukemia cell line (THP-1) was used in this in vitro study. THP-1 monocytes were differentiated to macrophage-like cells and exposed to LPS-detoxified polyethylene particles and prosthesis-derived TiAlV particles. Supernatant was used for TNFalpha protein measurement and total RNA was extracted from cells. LITAF was analyzed at the mRNA level using semiquantitative RT-PCR. Both polyethylene and TiAlV particles induced significant upregulation of LITAF mRNA that was followed by a significant TNFalpha response. These effects were dependent on the particle dose. Low particle concentrations exhibited no significant effect on expression of TNFalpha and LITAF mRNA. In comparison to exposure to polyethylene and TiAlV particles, LPS stimulation exhibited similar upregulation of LITAF mRNA, but led to an overwhelming TNFalpha response. Our findings provide evidence that LITAF is implicated in the pathogenesis of wear particle-induced osteolysis.
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PMID:Upregulation of LITAF mRNA expression upon exposure to TiAlV and polyethylene wear particles in THP-1 macrophages. 1740 80

Cultured lung cells provide an alternative to animal exposures for comparing the effects of different types of air pollution particles. Studies of particulate matter in vitro have reported proinflammatory cytokine signaling in response to many types of environmental particles, but there have been few studies comparing identical treatments in multiple cell types or identical cells with alternative cell culture protocols. We compared soil-derived, diesel, coal fly ash, titanium dioxide, and kaolin particles along with soluble vanadium and lipopolysaccharide, applied to airway-derived cells grown in submerged culture. Cell types included A549, BEAS-2B, RAW 264.7, and primary macrophages. The cell culture models (specific combinations of cell types and culture conditions) were reproducibly different in the cytokine signaling responses to the suite of treatments. Further, Interleukin-6 (IL-6) response to the treatments changed when the same cells, BEAS-2B, were grown in KGM versus LHC-9 media or in media containing bovine serum. The effect of changing media composition was reversible over multiple changes of media type. Other variables tested included culture well size and degree of confluence. The observation that sensitivity of a cell type to environmental agonists can be manipulated by modifying culture conditions suggests a novel approach for studying biochemical mechanisms of particle toxicity.
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PMID:Effects of cell type and culture media on Interleukin-6 secretion in response to environmental particles. 1817 71

Nanostructured materials are ubiquitous in tissue engineering, drug delivery, and biosensing applications. Nonetheless, little is known about the inflammatory response of materials differing in surface nanoarchitecture. Here we report human monocyte viability and morphology, in addition to inflammatory cytokines (IL-1alpha and B, IL-6, IL-10, IFN-alpha and gamma, TNF-alpha, IL-12, MIP-1alpha and beta), and reactive oxygen species production on several nanostructured surfaces, compared to flat surfaces of the same material. The surfaces studied were titiania nanotubes, short and long silicon oxide, and polycaprolactone nanowires. The results indicate that inflammation on titanium, polycaprolactone, and silicon oxide materials can be reduced by restructuring the surface with nanoarchitecture. Nanostructured surfaces display a reduced inflammation response compared to a respective flat control, with significant differences between titanium and nanotubular titanium. Little difference is observed in the inflammatory response between short and long nanowires of PCL and silicon oxide. All surfaces are significantly less inflammatory than the positive control, lipopolysaccharide. Additionally, we show that flat titanium is more inflammatory than silicon oxide and polycaprolactone. This study shows that nanoarchitecture can be used to reduce the inflammatory response of human monocytes in vitro.
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PMID:In vitro inflammatory response of nanostructured titania, silicon oxide, and polycaprolactone. 1898 78

This study was performed to microscopically observe and measure inflammatory cytokine production by human macrophages phagocytosing submicron titanium (Ti) particles. Observations with secondary electron microscopy (SEM), SEM/electron probe microanalysis (EPMA) and transmission electron microscopy (TEM) indicated that macrophages [phorbol-12-myristate-13-acetate (PMA)-differentiated THP-1 cells] at 24 h in culture actively phagocytosed and accumulated submicron Ti particles in intracellular phagosomes, in which refinement of Ti particles occurred. The macrophages were also cultured for 24 h in four media with and without submicron Ti particles and lipopolysaccharide (LPS; components of bacteria). Whilst neither stimulus reduced cell viability, submicron Ti particles and LPS activation independently and synergistically caused the macrophages to produce three inflammatory cytokines (TNF-alpha, IL-1beta and IL-6) at high levels in the culture supernatants. The inflammatory and osteolysis conditions caused by macrophages phagocytosing submicron Ti particles would be worsened by challenge with LPS in patients wearing Ti prostheses.
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PMID:Microscopic observations and inflammatory cytokine productions of human macrophage phagocytising submicron titanium particles. 1964 53

Amorphous peroxotitantes (APT) are insoluble titanium-based particles that bind a variety of metal compounds with high affinity; these particles could be sequestered locally in a solid phase to deliver metal-based drugs. Previous studies have confirmed the 'biodelivery' of metals from metal-APT complexes to fibroblasts, but not monocytes. Our goal in the current study was to use monocytic cytokine secretion to assess delivery of gold or platinum-based compounds from APT to human THP1 monocytes. Cytokine secretion was not triggered by APT alone or metal-APT complexes. In monocytes activated by lipopolysaccharide (LPS), APT alone enhanced or suppressed IL1beta or IL6 secretion, yet TNFalpha secretion was unaffected. Complexes of APT and Au(III) or cis-platin altered LPS-activated IL6 or IL1beta secretion most, TNFalpha least. Our results suggest that the APT deliver metals to monocytes.
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PMID:Titanates deliver metal ions to human monocytes. 1994 Oct 42

Endosseous dental implants use is increasing in patients with systemic conditions that compromise wound healing. Manufacturers recently have redesigned implants to ensure more reliable and faster osseointegration. One design strategy has been to create a porous phosphate-enriched titanium oxide (TiUnite) surface to increase surface area and enhance interactions with bone. In the current study, the corrosion properties of TiUnite implants were studied in cultures of monocytic cells and solutions simulating inflammatory and hyperglycemic conditions. Furthermore, to investigate whether placement into bone causes enough mechanical damage to alter implant corrosion properties, the enhanced surface implants as well as machined titanium implants were placed into human cadaver mandibular bone, the bone removed, and the corrosion properties measured. Implant corrosion behavior was characterized by open circuit potentials, linear polarization resistance, and electrical impedance spectroscopy. In selected samples, THP1 cells were activated with lipopolysaccharide prior to implant exposure to simulate an inflammatory environment. No significant differences in corrosion potentials were measured between the TiUnite implants and the machined titanium implants in previous studies. TiUnite implants exhibited lower corrosion rates in all simulated conditions than observed in PBS, and EIS measurements revealed two time constants which shifted with protein-containing electrolytes. In addition, the TiUnite implants displayed a significantly lower corrosion rate than the machined titanium implants after placement into bone. The current study suggests that the corrosion risk of the enhanced oxide implant is lower than its machined surface titanium implant counterpart under simulated conditions of inflammation, elevated dextrose concentrations, and after implantation into bone.
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PMID:Corrosion of phosphate-enriched titanium oxide surface dental implants (TiUnite) under in vitro inflammatory and hyperglycemic conditions. 2002 65

Nanoparticles are widely used in nanomedicines, including for targeted delivery of pharmacological, therapeutic, and diagnostic agents. Since nanoparticles might translocate across cellular barriers from the circulation into targeted organs, it is important to obtain information concerning the pathophysiologic effects of these particles through systemic migration. In the present study, acute pulmonary responses were examined after intraperitoneal (ip) administration of ultrafine titanium dioxide (TiO(2), 40 mg/kg) in mice at rest or in lungs primed with lipopolysaccharide (LPS, ip, 5 mg/kg). Ultrafine TiO(2) exposure increased neutrophil influx, protein levels in bronchoalveolar lavage (BAL) fluid, and reactive oxygen species (ROS) activity of BAL cells 4 h after exposure. Concomitantly, the levels of proinflammatory mediators, such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and macrophage inflammatory protein (MIP)-2 in BAL fluid and mRNA expression of TNF-alpha and IL-1beta in lung tissue were elevated post ultrafine TiO(2) exposure. Ultrafine TiO(2) exposure resulted in significant activation of inflammatory signaling molecules, such as c-Src and p38 MAP kinase, in lung tissue and alveolar macrophages, and the nuclear factor (NF)-kappaB pathway in pulmonary tissue. Furthermore, ultrafine TiO(2) additively enhanced these inflammatory parameters and this signaling pathway in lungs primed with lipopolysaccharide (LPS). Contrary to this trend, a synergistic effect was found for TNF-alpha at the level of protein and mRNA expression. These results suggest that ultrafine TiO(2) (P25) induces acute lung inflammation after ip administration, and exhibits additive or synergistic effects with LPS, at least partly, via activation of oxidant-dependent inflammatory signaling and the NF-kappaB pathway, leading to increased production of proinflammatory mediators.
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PMID:Pulmonary inflammation after intraperitoneal administration of ultrafine titanium dioxide (TiO2) at rest or in lungs primed with lipopolysaccharide. 2015 81


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