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)

Heparin is an excellent inhibitor of P- and L-selectin binding to the carbohydrate determinant, sialyl Lewis(x). As a consequence of its anti-selectin activity, heparin attenuates metastasis and inflammation. Here we show that fucosylated chondroitin sulfate (FucCS), a polysaccharide isolated from sea cucumber composed of a chondroitin sulfate backbone substituted at the 3-position of the beta-D-glucuronic acid residues with 2,4-disulfated alpha-L-fucopyranosyl branches, is a potent inhibitor of P- and L-selectin binding to immobilized sialyl Lewis(x) and LS180 carcinoma cell attachment to immobilized P- and L-selectins. Inhibition occurs in a concentration-dependent manner. Furthermore, FucCS was 4-8-fold more potent than heparin in the inhibition of the P- and L-selectin-sialyl Lewis(x) interactions. No inhibition of E-selectin was observed. FucCS also inhibited lung colonization by adenocarcinoma MC-38 cells in an experimental metastasis model in mice, as well as neutrophil recruitment in two models of inflammation (thioglycollate-induced peritonitis and lipopolysaccharide-induced lung inflammation). Inhibition occurred at a dose that produces no significant change in plasma activated partial thromboplastin time. Removal of the sulfated fucose branches on the FucCS abolished the inhibitory effect in vitro and in vivo. Overall, the results suggest that invertebrate FucCS may be a potential alternative to heparin for blocking metastasis and inflammatory reactions without the undesirable side effects of anticoagulant heparin.
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PMID:Selectin blocking activity of a fucosylated chondroitin sulfate glycosaminoglycan from sea cucumber. Effect on tumor metastasis and neutrophil recruitment. 1737 80

Constituents in rosemary have shown a variety of pharmacological activities for cancer chemoprevention and therapy in in vitro and in vivo models. In order to further explore the chemopreventive properties of crude extracts of rosemary (Rosmarinus officinalis L), we studied its anti-proliferative property on several human cancer cell lines and its antioxidant and anti-inflammatory properties in vitro in a mouse RAW 264.7 macrophage/monocyte cell line. Our study shows that crude ethanolic rosemary extract (RO) has differential anti-proliferative effects on human leukemia and breast carcinoma cells. The 50% inhibitory concentration (IC50) was estimated at 1/700, 1/400, 1/150 and 1/500 dilutions, for the HL60, K562, MCF7 and MDA-MB-468 cells, respectively. Non-cytotoxic concentrations of RO at 1/1000 dilution minimally induced HL60 cell differentiation into granulocyte lineage at 9.5+/-2.2% compared to 2.8+/-0.8% in the untreated control (p<0.001), and did not induce HL60 cell differentiation into monocyte/macrophage lineage. The 6-hydroxy-2,5,7,8-tetramethyl-chroman-2-carboxylic acid (Trolox) equivalent antioxidant capacity assay showed that RO has substantial antioxidant activity with RO at 1/10 and 1/5 dilutions having 8.1 and 12.6 microM Trolox equivalents, respectively. RO at non-cytotoxic 1/2000 and 1/1000 dilutions did not affect nitric oxide (NO) production by non-stimulated RAW 264.7 cells. However, at the same dilutions RO significantly reduced NO production by lipopolysaccharide (LPS)-activated cells in a dose-dependent manner from 32.6+/-2.3 microM in the LPS-activated cells to 19.2+/-2.2 microM (p<0.01), and 7.7+/-1.2 microM (p<0.001), respectively. RT-PCR analyses showed that RAW 264.7 cells treated with 1/1000 and 1/500 dilutions for 5 h did not affect TNFalpha, IL-1beta, iNOS and COX-2 mRNA expression in these cells when compared to the untreated controls, nor did the 1/1000 dilution of RO affect TNFalpha, IL-1beta, iNOS and COX-2 mRNA expression in the LPS-activated cells. At 1/500 dilution, RO significantly reduced IL-1beta (p<0.01) and COX-2 (p<0.05) mRNA expression and non-significantly reduced TNFalpha and iNOS mRNA expression in the LPS-activated cells. In view of the chemopreventive potentials, further studies are needed to explore other biological properties of this popular spice used by many cultures in the world.
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PMID:Anti-proliferative and antioxidant properties of rosemary Rosmarinus officinalis. 1748 14

Accumulating lines of evidence suggest a possibility that glycine is useful as an immuno-modulating amino acid. Glycine most likely prevents the lipopolysaccharide (LPS)-induced elevation of intracellular Ca(2+) concentration in Kupffer cells, thereby minimizing LPS receptor signaling and cytokine production. Moreover, it was reported that dietary glycine inhibits the growth of tumors. Vascular endothelial growth factor (VEGF) plays a critical role in cancer progression by promoting new blood vessel formation. Activation of VEGF receptor has been shown to result in activation of phospholipase C-gamma and increases in intracellular Ca(2+) concentration. The VEGF-induced cell proliferation is dependent on intracellular Ca(2+) concentration. The effects of glycine on VEGF-induced increases in intracellular Ca(2+) concentration in endothelial cell line (CPA) were studied. The VEGF increased intracellular Ca(2+) concentration rapidly, but glycine blunted increases in intracellular Ca(2+) concentration due to VEGF. Further, the inhibitory effects of glycine were prevented by low concentrations of strychnine (1 micromol/L) or incubation with chloride-free buffer. Moreover, glycine increased influx of radiolabeled chloride into CPA cells approximately 10-fold. Furthermore, mRNA 92% identical to the beta-subunit of the glycine-gated chloride channel from spinal cord was identified in endothelial cells using reverse transcription-polymerase chain reaction. Finally, glycine significantly diminished serum-stimulated proliferation and migration of endothelial cells. These data indicate that the inhibitory effect of glycine on growth and migration of endothelial cells is due to activation of a glycine-gated chloride channel. This hyperpolarizes the cell membrane and blocks influx of Ca(2+), thereby minimizing growth factor-mediated signaling. Therefore, glycine can be used not only for treatment of inflammation, but also for chemoprevention and treatment of carcinoma.
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PMID:Glycine as a potent anti-angiogenic nutrient for tumor growth. 1756 69

Pancreatic secretory trypsin inhibitor (PSTI) is a serine protease inhibitor, expressed in gut mucosa, whose function is unclear. We, therefore, examined the effects of PSTI on gut stability and repair. Transgenic mice overexpressing human PSTI within the jejunum (FABPi(-1178 to +28) hPSTI construct) showed no change in baseline morphology or morphometry but reduced indomethacin-induced injury in overexpressing hPSTI region by 42% (P < 0.01). Systemic recombinant hPSTI did not affect baseline morphology or morphometry but truncated injurious effects in prevention and recovery rat models of dextran-sodium-sulfate-induced colitis. In vitro studies showed PSTI stimulated cell migration but not proliferation of human colonic carcinoma HT29 or immortalized mouse colonic YAMC cells. PSTI also induced changes in vectorial ion transport (short-circuit current) when added to basolateral but not apical surfaces of polarized monolayers of Colony-29 cells. Restitution and vectorial ion transport effects of PSTI were dependent on the presence of a functioning epidermal growth factor (EGF) receptor because cells with a disrupted (EGFR(-/-) immortalized cells) or neutralized (EGFR blocking antibodies or tyrosine kinase inhibitor) receptor prevented these effects. PSTI also reduced the cytokine release of lipopolysaccharide-stimulated dendritic cells. We conclude that administration of PSTI may provide a novel method of stabilizing intestinal mucosa against noxious agents and stimulating repair after injury.
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PMID:Human pancreatic secretory trypsin inhibitor stabilizes intestinal mucosa against noxious agents. 1798 25

Short palate, lung and nasal epithelium clone 1 (SPLUNC1) gene coded a secreted protein found at the surface of nasopharyngeal epithelium, which may be an innate immunity defensive molecular and a risk factor for nasopharyngeal carcinoma (NPC). Here, we observed the effects of SPLUNC1 on the Gram negative bacteria Pseudomonas aeruginosa, evaluated the ability of SPLUNC1 protein binding to lipopolysaccharide. To observe the effect of SPLUNC1 protein on Epstein-Barr virus (EBV), we raised three EBV-transformed B-lymphocyte lines and treated the cells by SPLUNC1 protein; cellular disruption, apoptosis, EBV DNA content, and viral oncogene expression were analyzed. We found that SPLUNC1 protein can bind to bacterial lipopolysaccharide, inhibit the growth of P. aeruginosa, enhance the disruption and apoptosis of EBV-infected B-lymphocytes, downregulate protein expression of EBV latent membrane protein 1, while upregulate protein expression of EBV envelope glycoprotein gp350/220. The total EBV DNA in the culture medium was decreased significantly after 7 days of treatment by SPLUNC1. This study shows that SPLUNC1 not only has the role of antibacteria and antivirus, but also inhibits the potential oncogenicity of EBV in respiratory epithelium.
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PMID:Effect of SPLUNC1 protein on the Pseudomonas aeruginosa and Epstein-Barr virus. 1804 66

The epidermal growth factor receptor (EGFR) is frequently overexpressed in various tumours of epidermal origin and is held responsible for tumourigenicity and tumour persistence. Increased nuclear factor (NF)-kappaB activity has been suggested to be involved in the malignant behaviour of EGFR-overexpressing cells. However, the mechanisms that regulate EGF-induced NF-kappaB activation are still largely unknown. Here we show that EGF can induce NF-kappaB-dependent gene expression independently from IkappaBalpha degradation or p100 processing in EGFR-overexpressing HEK293T cells. Moreover, EGF-induced NF-kappaB activation could be inhibited by overexpression of ABINs, which were previously identified as intracellular inhibitors of tumour necrosis factor, interleukin-1 and lipopolysaccharide-induced NF-kappaB activation. Knockdown of ABIN-1 by RNA interference boosted the NF-kappaB response upon EGF stimulation. The C-terminal ubiquitin-binding domain containing region of ABINs was crucial and sufficient for NF-kappaB inhibition. Adenoviral gene transfer of ABINs reduced constitutive NF-kappaB activity as well as the proliferation of EGFR-overexpressing A431 and DU145 human carcinoma cells. Altogether, these results demonstrate an important role for an ABIN-sensitive non-classical NF-kappaB signalling pathway in the proliferation of EGFR-overexpressing tumour cells, and indicate a potential use for ABIN gene therapy in the treatment of cancer.
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PMID:ABINs inhibit EGF receptor-mediated NF-kappaB activation and growth of EGF receptor-overexpressing tumour cells. 1862 28

Oral and oro-pharyngeal squamous cell carcinomas (OSCC) exhibit surface breach, and recent studies have demonstrated bacterial contamination of primary and metastatic OSCC. Increasing concentrations of inflammatory products, such as interleukin (IL)-6 and vascular endothelial growth factor (VEGF), correlate with, and contribute to, cancer progression, but their regulation in OSCC is poorly understood. We hypothesized that monocyte-lineage cells and bacterial contamination may contribute important inflammatory products that can support OSCC progression. We found that relative to non-specific chronic mucositis, oral carcinoma-in-situ/superficially-invasive OSCC contained more monocyte-lineage cells. In vitro, we used lipopolysaccharide (LPS) to model bacterial contamination, and evaluated the effects of oral and oropharyngeal (O)SCC-monocyte interactions and of LPS on OSCC cells and on the production of IL-6 and VEGF. OSCC cell lines varied in constitutive cytokine and chemokine production, and OSCC-monocyte interactions in the absence of LPS stimulated IL-6 and VEGF occasionally, while LPS-OSCC-monocyte interactions were always strongly stimulatory. Importantly, LPS independently stimulated some OSCC lines to secrete monocyte-dendritic cell chemoattractants CCL2 and/or CCL20, as well as IL-6 and/or VEGF. While very little constitutive Y705-STAT3 phosphorylation (pY705-STAT3) was detectable in HNSCC lines, IL-6 rapidly induced pY705-STAT3 in OSCC lines that produced little IL-6 constitutively. Supernatants from LPS-OSCC-monocyte co-cultures always rapidly and strongly activated STAT3, which was partly due to IL-6. We conclude that monocytes and microbial contamination have the potential to contribute to OSCC progression, as STAT3 activation in OSCC cells depends on soluble factors, which are consistently available through LPS-OSCC-monocyte interactions.
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PMID:Lipopolysaccharide-squamous cell carcinoma-monocyte interactions induce cancer-supporting factors leading to rapid STAT3 activation. 1960 82

Recently, it has been reported that bacterial infections play an important role in the development of cancers of the upper aero digestive tract. To examine the influence of bacterial infections on oral cancer, human oral carcinoma T3M-1 cells were treated with lipopolysaccharide (LPS) for 24 h as a model of infection. The LPS treatment increased the mRNA expression of CXCR4 and invasiveness in T3M-1 cells stimulated with CXCL12. The Rho family of small guanosine triphosphatases regulates the dynamics of the actin cytoskeleton that underlie cellular functions such as cell shape changes, migration and polarity. In T3M-1 cells treated with LPS and stimulated with CXCL12, Rac and Cdc42 were activated and caused an increase in the development of filopodia. The present findings suggest that bacterial infections enhance the invasiveness of T3M-1 cells via CXCL12/CXCR4 interaction and Cdc42-activation. Furthermore, filopodia are critical to this process.
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PMID:Lipopolysaccharides increase the amount of CXCR4, and modulate the morphology and invasive activity of oral cancer cells in a CXCL12-dependent manner. 1966 22

Toll-like receptors (TLR) are pattern recognition receptors that play a pivotal role in the initiation of immune responses. Here we report that the murine mammary carcinoma 4T1 constitutively expressed genes encoding TLR2, 3, 4 and 5. Moreover, treatment of the 4T1 cell line with peptidoglycan (PGN), polyinosinic-polycytidylic acid (Poly(I:C)) or lipopolysaccharide (LPS), agonists for TLR2, 3 or 4 respectively, induced nuclear translocation of NFkappaB and secretion of CCL2, CCL5 and CXCL1 in a dose dependent manner. Although treating the tumor cells with the TLR agonists did not modulate growth or viability of the tumor cells in vitro, 4T1 exhibited a decreased growth rate in vivo following treatment with LPS that was dependent upon the presence of CD8(+) T cells. Analysis of 3 additional murine mammary carcinomas revealed that they also secreted CCL2, CCL5 and CXCL1 in response to TLR agonist treatment, and LPS treated 168 and SM1 tumors exhibited decreased growth rates in vivo, but not in vitro. These data indicated that 4 out of 4 murine mammary carcinomas secreted proinflammatory chemokines following treatment with TLR agonists, and 3 out of 4 of the mammary carcinomas responded to LPS treatment in a manner that decreased tumor growth in vivo.
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PMID:Lipopolysacchride-treated mammary carcinomas secrete proinflammatory chemokines and exhibit reduced growth rates in vivo, but not in vitro. 1986 May 85

Chronic infection and inflammation are among the most important factors contributing to cancer development and growth. Toll-like receptors (TLRs) are important families of pattern recognition receptors, which recognize conserved components of microbes and trigger the immune response against invading microorganisms. TLR4 is the signaling receptor for lipopolysaccharide (LPS), the endotoxic component of Gram-negative bacteria. Recent studies demonstrate that TLRs are expressed in some tumor cells, and that the expression of TLRs in these cells is associated with tumorigenesis. Cervical intraepithelial neoplasia (CIN) is a key stage in the development of cervical cancer and human papillomavirus (HPV) infection is an essential factor in cervical carcinogenesis. As the cervix is in constant contact with bacteria, especially Gram-negative bacteria, we hypothesize that TLR4-mediated bacterial stimulation may be involved in the tumorigenesis of cervical cancer. In the present study, the expression and distribution of TLR4 in CIN and cervical squamous carcinoma were investigated by immunohistochemistry. To our surprise, we observed a decrease in the expression of TLR4 during the progression of cervical neoplasia and this down-regulation of TLR4 appeared to be associated with the expression of P(16INK4A) which is a crucial marker of HPV integration into host cells. These data offer further insight regarding the association of HPV infection and TLR signaling during the carcinogenesis of cervical cancer.
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PMID:Expression of toll-like receptor 4 is down-regulated during progression of cervical neoplasia. 2017 75


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