Lipid-binding Protein Research Articles

Frequency-control of protein translocation across an oscillating nanopore.

The translocation of a lipid binding protein (LBP) is studied using a phenomenological coarse-grained computational model that simplifies both chain and pore geometry. We investigated via molecular dynamics the interplay between transport and unfolding in the presence of a nanopore whose section oscillates periodically in time with a frequency ω, a motion often referred to as the radial breathing mode (RBM). We found that the LPB when mechanically pulled into the vibrating nanopore exhibits a translocation dynamics that in some frequency range is accelerated and shows a frequency locking to the pore dynamics. The main effect of pore vibrations is the suppression of stalling events of the translocation dynamics, hence, proper frequency tuning allows both regularization and control of the overall transport process. Finally, the interpretation of the simulation results is easily achieved by resorting to a first passage theory of elementary driven-diffusion processes.

Sphingolipidoses membrane lipids regulate and modify sphingolipid catabolism, its enzymes, lipid binding and transfer proteins

Sphingolipidoses membrane lipids regulate and modify sphingolipid catabolism, its enzymes, lipid binding and transfer proteins

Korean Chungtaejeon tea extract attenuates weight gain in C57BL/6J-Lep ob/ob mice and regulates adipogenesis and lipolysis in 3T3-L1 adipocytes

ObjectiveTraditional Korean Chungtaejeon (CTJ) tea is a type of fermented tea, which has received increasing attention in recent years because of its purported health benefits. The present study was designed to investigate the effect and mechanism of CTJ tea extract on body weight gain using C57BL/6J-Lep ob/ob mice and 3T3-L1 adipocytes, respectively. MethodsThe effects of CTJ on cell viability, lipid accumulation, and expression of protein and mRNA were measured in 3T3-L1 adipocytes by using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, oil red O staining, Western blotting, and reverse transcriptase-polymerase chain reaction analyses. C57BL6J-Lep ob/ob mice were administered with CTJ (200 or 400 mg/kg body weight) for ten weeks. Then, body weight, food intake, total cholesterol, and triglyceride were measured in ob/ob mice. ResultsCTJ tea extract treated at 250 μg/mL (CTJ250) significantly suppressed lipid accumulation in the differentiated 3T3-L1 adipocytes. Likewise, CTJ250 significantly decreased the protein expression of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α, and adipocyte lipid-binding protein, and regulated the mRNA expression of PPARγ, sterol regulatory element-binding protein-1c gene, fatty acid synthase, adipocyte lipid-binding protein, hormone-sensitive lipase, carnitine palmitoyl transferase 1, cluster of differentiation 36, and acetyl-CoA carboxylase in the differentiated 3T3-L1 adipocytes. Mice administered with CTJ showed dose-dependent decrease in body weight gain, starting from week 4 of the experiment. CTJ tea extract administered at 400 mg/kg body weight significantly decreased fat mass, food efficacy ratio, and levels of plasma triglyceride and total cholesterol. ConclusionCTJ attenuated weight gain in ob/ob mice and regulated the activity of the molecules involved in adipogenesis and lipolysis in 3T3-L1 adipocytes. CTJ is a potentially valuable herbal therapy for the prevention of obesity and/or obesity-related disorders.

EV-Associated MMP9 in High-Grade Serous Ovarian Cancer Is Preferentially Localized to Annexin V-Binding EVs.

High-grade serous ovarian cancer (HGSOC) is the most aggressive type of ovarian cancer and is responsible for most deaths caused by gynecological cancers. Numerous candidate biomarkers were identified for this disease in the last decades, but most were not sensitive or specific enough for clinical applications. Hence, new biomarkers for HGSOC are urgently required. This study aimed to identify new markers by isolating different extracellular vesicle (EV) types from the ascites of ovarian cancer patients according to their affinities for lipid-binding proteins and analyzing their protein cargo. This approach circumvents the low signal-to-noise ratio when using biological fluids for biomarker discovery and the issue of contamination by large non-EV complexes. We isolated and analyzed three distinct EV populations from the ascites of patients with ovarian cancer or cirrhosis and observed that Annexin V-binding EVs have higher levels of matrix metalloproteinase 9 in malignant compared to portal-hypertensive ascites. As this protein was not detected in other EV populations, this study validates our approach of using different EV types for optimal biomarker discovery. Furthermore, MMP9 in Annexin V-binding EVs could be a HGSOC biomarker with enhanced specificity, because its identification requires detection of two distinct components, that is, lipid and protein.

LDL cholesterol hitches a ride.

A new lipid-binding protein transports low-density lipoprotein across the blood vessel endothelium and might promote atherosclerosis.

A compendium of human genes regulating feeding behavior and body weight, its functional characterization and identification of GWAS genes involved in brain-specific PPI network.

BackgroundObesity is heritable. It predisposes to many diseases. The objectives of this study were to create a compendium of genes relevant to feeding behavior (FB) and/or body weight (BW) regulation; to construct and to analyze networks formed by associations between genes/proteins; and to identify the most significant genes, biological processes/pathways, and tissues/organs involved in BW regulation.ResultsThe compendium of genes controlling FB or BW includes 578 human genes. Candidate genes were identified from various sources, including previously published original research and review articles, GWAS meta-analyses, and OMIM (Online Mendelian Inheritance in Man). All genes were ranked according to knowledge about their biological role in body weight regulation and classified according to expression patterns or functional characteristics. Substantial and overrepresented numbers of genes from the compendium encoded cell surface receptors, signaling molecules (hormones, neuropeptides, cytokines), transcription factors, signal transduction proteins, cilium and BBSome components, and lipid binding proteins or were present in the brain-specific list of tissue-enriched genes identified with TSEA tool. We identified 27 pathways from KEGG, REACTOME and BIOCARTA whose genes were overrepresented in the compendium. Networks formed by physical interactions or homological relationships between proteins or interactions between proteins involved in biochemical/signaling pathways were reconstructed and analyzed. Subnetworks and clusters identified by the MCODE tool included genes/proteins associated with cilium morphogenesis, signal transduction proteins (particularly, G protein–coupled receptors, kinases or proteins involved in response to insulin stimulus) and transcription regulation (particularly nuclear receptors). We ranked GWAS genes according to the number of neighbors in three networks and revealed 22 GWAS genes involved in the brain-specific PPI network. On the base of the most reliable PPIs functioning in the brain tissue, new regulatory schemes interpreting relevance to BW regulation are proposed for three GWAS genes (ETV5, LRP1B, and NDUFS3). ConclusionsA compendium comprising 578 human genes controlling FB or BW was designed, and the most significant functional groups of genes, biological processes/pathways, and tissues/organs involved in BW regulation were revealed. We ranked genes from the GWAS meta-analysis set according to the number and quality of associations in the networks and then according to their involvement in the brain-specific PPI network and proposed new regulatory schemes involving three GWAS genes (ETV5, LRP1B, and NDUFS3) in BW regulation. The compendium is expected to be useful for pathology risk estimation and for design of new pharmacological approaches in the treatment of human obesity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-016-0466-2) contains supplementary material, which is available to authorized users.

Refined purification strategy for reliable proteomic profiling of HDL2/3: Impact on proteomic complexity.

Proteomics have extended the list of high-density lipoprotein (HDL) associated proteins to about 90. One of the major issues of global protein characterization is establishing specificity of association as opposed to contamination, a fact which has never been addressed for isolated HDL. We have developed a refined purification strategy to isolate HDL by density, followed by purification by size to generate “highly purified” fractions of HDL2/3, which allow the reliable quantification of the HDL proteome for biomarker discovery. Mass spectrometry analysis revealed that the proteome of HDL2/3 is composed of 10–16 different proteins, which is in striking contrast to previous reports. Importantly, proteomic analysis revealed that many proteins which have recently been described to be associated with HDL, including α-1-antitrypsin, α-2-HS-glycoprotein, serotransferrin, apolipoprotein A-IV and others, are not associated with HDL2/3 and are exclusively found in a different molecular weight fraction containing human serum albumin, lipid-poor apolipoprotein A-I and other proteins. Interestingly, proteins found in this lower molecular weight fraction commonly share lipid-binding properties and enrichment of serum with free fatty acids/lysophophatidylcholine led to a significant increase in co-isolation of lipid-binding proteins such as albumin and α-1-antitrypsin. We propose that this refined method might become a standard in proteomic assessment of HDL2/3 making data from clinical cohorts more comparable and reproducible.

Molecular characterization and subcellular localization of salt-inducible lipid transfer proteins in rice

Rice (Oryza sativa L.) is a salt-sensitive species. Salt stress can cause injury to plant cellular membrane. Plant lipid transfer proteins (LTPs) are abundant lipid binding proteins that are important in membrane vesicle biogenesis and trafficking, however, the biological importance of LTPs on salt-stress response in rice remains unclear. Therefore, saltresponsive rice LTPs were identified and characterized in this study. Microarray analysis showed seven genes positively regulated by salinity, including five Ltp genes (LtpII.3, LtpII.5, LtpII.6, LtpV.1, and LtpV.2) and two Ltp-like (LtpL; LtpL1 and LtpL2) genes. Amino acid alignment revealed that all these Ltp and LtpL genes contained the N-terminal signal peptide. Apart from LtpL1, all salt-inducible Ltp genes have the conserved eight cysteine residue motifs backbone. Verification of gene expression to different stimuli in rice seedlings revealed that salt-regulated Ltp genes differentially responded to drought, cold, H2O2, abscisic acid (ABA) and CaCl2. Furthermore, the expression of Ltp and LtpL genes was tissue-specifically regulated by ABA-dependent and independent pathway. In silico analysis of an 1.5-kb 5’-upstream region of these genes showed regulatory cis-elements associated with ABA, calcium, and cold/drought responses. Three LtpII subfamily genes, including LtpII.3, LtpII.5, and LtpII.6, were strictly expressed in flowers and seeds, and LtpIII.1 mRNA strongly accumulated in stem tissue. Subcellular localization analysis of LTP-DsRed fusion proteins revealed that the five LTPs and two LTPLs localized at the endoplasmic reticulum. The results provide new clues to further understand the biological functions of Ltp genes.

Electrospun Lipid Binding Proteins Composite Nanofibers with Antibacterial Properties.

Electrospinning is here used for the first time to prepare nanofibers including a host/guest complex in a keratin/poly(ethylene oxide) matrix. The host is a lipid binding protein and the guest is an insoluble bactericidal molecule, irgasan, bound within the protein internal cavity. The obtained nanofibers, characterized by scanning electron microscopy, exhibit excellent antibacterial activity toward Gram positive and negative bacteria, even with a moderate protein/irgasan cargo. Solution NMR studies, employed to provide molecular information on the cargo system, points to a micromolar affinity, compatible with both the electrospinning process and slow guest release. The versatility of the carrier protein, capable of interacting with a variety of druggable hydrophobic molecules, is exploitable for the development of innovative biomedical devices, whose properties can be tuned by the selected guest.

A High-Throughput Fluorometric Assay for Lipid-Protein Binding.

An increasing number of intracellular and extracellular proteins are shown to interact with membrane lipids under physiological conditions. For rapid and robust quantitative measurement of lipid-protein interaction, we developed a sensitive fluorescence quenching-based assay that is universally applicable to all proteins and lipids. The assay employs fluorescence protein (FP)-tagged proteins whose fluorescence emission intensity is decreased when they bind vesicles containing quenching lipids. This simple assay can be performed with a fluorescence plate reader or a spectrofluorometer and optimized for different proteins with various combinations of FPs and quenching lipids. The assay allows a rapid, sensitive, and accurate determination of lipid specificity and affinity for various lipid-binding proteins, and high-throughput screening of molecules that modulate their membrane binding.

Fluorescence-Based In Situ Quantitative Imaging for Cellular Lipids.

Membrane lipids are dynamic molecules and their local concentrations serve as regulatory signals for diverse biological processes. To achieve quantitative in situ imaging of various lipids, we developed a ratiometric analysis using fluorescence biosensors, each of which is composed of an engineered lipid-binding protein and a covalently attached solvatochromic fluorophore. To cover a wide range of lipid concentration, lipid-binding proteins are engineered to have variable dynamic ranges. These tunable sensors allow robust and sensitive in situ quantitative lipid imaging in mammalian cells, providing new insight into the spatiotemporal dynamics and fluctuation of key signaling lipids. The sensor strategy is also applicable to in situ quantification of multiple cellular lipids or a single lipid in the opposing leaflets of cell membranes.

Immunocytochemical characterisation of neural stem-progenitor cells from green terror cichlid Aequidens rivulatus.

In this study, cultures of neural stem-progenitor cells (NSPC) from the brain of green terror cichlid Aequidens rivulatus were established and various NSPCs were demonstrated using immunocytochemistry. All of the NSPCs expressed brain lipid-binding protein, dopamine- and cAMP-regulated neuronal phosphoprotein 32 (DARPP-32), oligodendrocyte transcription factor 2, paired box 6 and sex determining region Y-box 2. The intensity and localisation of these proteins, however, varied among the different NSPCs. Despite being intermediate cells, NSPCs can be divided into radial glial cells, oligodendrocyte progenitor cells (OPC) and neuroblasts by expressing the astrocyte marker glial fibrillary acidic protein (GFAP), OPC marker A2B5 and neuronal markers, including acetyl-tubulin, βIII-tubulin, microtubule-associated protein 2 and neurofilament protein. Nevertheless, astrocytes were polymorphic and were the most dominant cells in the NSPC cultures. By using Matrigel, radial glia exhibiting a long GFAP+ or DARPP-32+ fibre and neurons exhibiting a significant acetyl-tubulin+ process were obtained. The results confirmed that NSPCs obtained from A. rivulatus brains can proliferate and differentiate into neurons in vitro. Clonal culture can be useful for further studying the distinct NSPCs.

Age-dependent acute interference with stem and progenitor cell proliferation in the hippocampus after exposure to 1800 MHz electromagnetic radiation

ABSTRACTTo investigate the effects of exposure to an 1800 MHz electromagnetic field on cell death and cell proliferation in the developing brain, postnatal day 7 (P7) and P21 healthy Kunming mice were randomly assigned into the experimental and control groups. The experimental groups were exposed to an 1800 MHz electromagnetic field for 8 h daily for three consecutive days. The thymidine analog 5-bromo-2-deoxyuridine (BrdU) was injected intraperitoneally 1 h before each exposure session, and all animals were sacrificed 24 h after the last exposure. Cell death and proliferation markers were detected by immunohistochemistry in the dentate gyrus of the hippocampus. Electromagnetic exposure has no influence on cell death in the dentate gyrus of the hippocampus in P7 and P21 mice as indicated by active caspase-3 immunostaining and Fluoro-Jade labeling. The basal cell proliferation in the hippocampus was higher in P7 than in P21 mice as indicated by the number of cells labeled with BrdU and by immunohistochemical staining for phosphor-histone H3 (PHH3) and brain lipid-binding protein (BLBP). Electromagnetic exposure stimulated DNA synthesis in P7 neural stem and progenitor cells, but reduced cell division and the total number of stem cells in the hippocampus as indicated by increased BrdU labeling and reduced PHH3 and BLBP labeling compared to P7 control mice. There were no significant changes in cell proliferation in P21 mice after exposure to the electromagnetic field. These results indicate that interference with stem cell proliferation upon short-term exposure to an 1800 MHz electromagnetic field depends on the developmental stage of the brain.

Characterization of Lipid-Protein Interactions Using Nonquenched Fluorescent Liposomal Nanovesicles and Yeast Proteome Microarrays.

Studying lipid-protein interactions is central to understanding lipid signaling, a key regulatory system in cells. To better identify lipid-binding proteins, we developed a nonquenched fluorescent (NQF) liposome that is able to carry both fluorescent molecules and a lipid of interest. By combining the strength of NQF liposomes with protein microarray technology, the method presented here facilitates high-throughput screening of lipid-protein interactions. This protocol describes how to prepare NQF liposomes and apply the fabricated liposomes to yeast proteome microarrays.

Annexin A6 regulates adipocyte lipid storage and adiponectin release

Lipid storage and adipokine secretion are critical features of adipocytes. Annexin A6 (AnxA6) is a lipid-binding protein regulating secretory pathways and its role in adiponectin release was examined. The siRNA-mediated AnxA6 knock-down in 3T3-L1 preadipocytes impaired proliferation, and differentiation of AnxA6-depleted cells to mature adipocytes was associated with higher soluble adiponectin and increased triglyceride storage. The latter was partly attributed to reduced lipolysis. Accordingly, AnxA6 overexpression in 3T3-L1 adipocytes lowered cellular triglycerides and adiponectin secretion. Indeed, serum adiponectin was increased in AnxA6 deficient mice. Expression analysis identified AnxA6 protein to be more abundant in intra-abdominal compared to subcutaneous adipose tissues of mice and men. AnxA6 protein levels increased in white adipose tissues of obese mice and here, levels were highest in subcutaneous fat. AnxA6 protein in adipocytes was upregulated by oxidative stress which might trigger AnxA6 induction in adipose tissues and contribute to impaired fat storage and adiponectin release.

Analysis of Sogatella furcifera proteome that interact with P10 protein of Southern rice black-streaked dwarf virus.

Southern rice black-streaked dwarf virus (SRBSDV) is transmitted efficiently only by white-backed planthopper (WBPH, Sogatella furcifera) in a persistent propagative manner. Here we used a yeast two-hybrid system to investigate the interactions between the SRBSDV- P10 and the cDNA library of WBPH. Of 130 proteins identified as putative interactors, 28 were further tested in a retransformation analysis and β-galactosidase assay to confirm the interaction. The full-length gene sequences of 5 candidate proteins: vesicle-associated membrane protein 7 (VAMP7), vesicle transport V-SNARE protein (Vti1A), growth hormone-inducible transmembrane protein (Ghitm), nascent polypeptide-associated complex subunit alpha, and ATP synthase lipid-binding protein) were amplified by 5′ rapid amplification of cDNA ends (RACE) and used in a GST fusion protein pull-down assay. Three of these proteins interacted with SRBSDV-P10 in vitro experiment GST pull-down assay. In a gene expression analysis of 3 different growth stages and 6 different tissue organs of S. furcifera, the mRNA level of VAMP7 was high in adult males and gut. Vti1A was abundant in adult female, and malpighian tubule, gut and ovary. Ghitm was predominantly found in adult male and the malpighian tubule. These research findings are greatly helpful to understand the interaction between SRBSDV and insect vector.

Domain-Swapped Dimers of Intracellular Lipid-Binding Proteins: Evidence for Ordered Folding Intermediates

Human Cellular Retinol Binding Protein II (hCRBPII), a member of the intracellular lipid-binding protein family, is a monomeric protein responsible for the intracellular transport of retinol and retinal. Herein we report that hCRBPII forms an extensive domain-swapped dimer during bacterial expression. The domain-swapped region encompasses almost half of the protein. The dimer represents a novel structural architecture with the mouths of the two binding cavities facing each other, producing a new binding cavity that spans the length of the protein complex.Although wild-type hCRBPII forms the dimer, the propensity for dimerization can be substantially increased via mutation at Tyr60. The monomeric form of the wild-type protein represents the thermodynamically more stable species, making the domain-swapped dimer a kinetically trapped entity. Hypothetically, the wild-type protein has evolved to minimize dimerization of the folding intermediate through a critical hydrogen bond (Tyr60-Glu72) that disfavors the dimeric form.

Effects of macromolecular crowding on a small lipid binding protein probed at the single-amino acid level

Macromolecular crowding is a distinctive feature of the cellular interior, influencing the behaviour of biomacromolecules. Despite significant advancements in the description of the effects of crowding on global protein properties, the influence of cellular components on local protein attributes has received limited attention. Here, we describe a residue-level systematic interrogation of the structural, dynamic, and binding properties of the liver fatty acid binding protein (LFABP) in crowded solutions.Two-dimensional NMR spectral fingerprints and relaxation data were collected on LFABP in the presence of polymeric and biomolecular crowders. Non-interacting crowders produced minimal site-specific spectral perturbations on ligand-free and lipid-bound LFABP. Conformational adaptations upon ligand binding reproduced those observed in dilute solution, but a perturbation of the free oleate state resulted in less favorable uptake. When LFABP engaged in direct interactions with background molecules, changes in local chemical environments were detected for residues of the internal binding pocket and of the external surface.Enhanced complexity was introduced by investigating LFABP in cell lysates, and in membrane-bounded compartments. LFABP was able to capture ligands from prokaryotic and eukaryotic cell lysates, and from artificial cells (water-in-oil emulsion droplets).The data suggest that promiscuous interactions are a major factor influencing protein function in the cell.

Static Clathrin Assemblies at the Peripheral Vacuole-Plasma Membrane Interface of the Parasitic Protozoan Giardia lamblia.

Giardia lamblia is a parasitic protozoan that infects a wide range of vertebrate hosts including humans. Trophozoites are non-invasive but associate tightly with the enterocyte surface of the small intestine. This narrow ecological specialization entailed extensive morphological and functional adaptations during host-parasite co-evolution, including a distinctly polarized array of endocytic organelles termed peripheral vacuoles (PVs), which are confined to the dorsal cortical region exposed to the gut lumen and are in close proximity to the plasma membrane (PM). Here, we investigated the molecular consequences of these adaptations on the Giardia endocytic machinery and membrane coat complexes. Despite the absence of canonical clathrin coated vesicles in electron microscopy, Giardia possesses conserved PV-associated clathrin heavy chain (GlCHC), dynamin-related protein (GlDRP), and assembly polypeptide complex 2 (AP2) subunits, suggesting a novel function for GlCHC and its adaptors. We found that, in contrast to GFP-tagged AP2 subunits and DRP, CHC::GFP reporters have no detectable turnover in living cells, indicating fundamental differences in recruitment to the membrane and disassembly compared to previously characterized clathrin coats. Histochemical localization in electron tomography showed that these long-lived GlCHC assemblies localized at distinctive approximations between the plasma and PV membrane. A detailed protein interactome of GlCHC revealed all of the conserved factors in addition to novel or highly diverged proteins, including a putative clathrin light chain and lipid-binding proteins. Taken together, our data provide strong evidence for giardial CHC as a component of highly stable assemblies at PV-PM junctions that likely have a central role in organizing continuities between the PM and PV membranes for controlled sampling of the fluid environment. This suggests a novel function for CHC in Giardia and the extent of molecular remodeling of endocytosis in this species.

Abstract 3441: Associations between lipopolysaccharide (LPS) and LPS pathway biomarkers and gallbladder cancer are modulated by markers of systemic inflammation

Abstract Little is known about gallbladder cancer (GBC) etiology. Gallstones (GS) are a critical factor in GBC pathogenesis. Bacterial infections, such as Salmonella Typhi and Helicobacter pylori, also may contribute to the development of GBC. We previously observed strong associations between inflammation markers and GBC vs. GS patients and hypothesized that bacterial infections may explain in part associations between GBC and inflammation. In the current study of 41 GBC cases and 124 GS patients from Shanghai, China, we evaluated relationships between GBC and the bacterial infection-related proteins plasma lipopolysaccharide (LPS) and two LPS-pathway proteins, soluble CD14 (sCD14) and lipid binding protein (LBP), as measured by ELISA. Further, we explored the extent to which these associations were mediated through systemic inflammation. Logistic regression was conducted to assess associations of GBC with plasma LPS, sCD14, and LBP levels. To evaluate mediation through inflammation, an inflammation score was calculated by summing the value of 15 previously measured GBC-associated serum inflammation markers (β-coefficient multiplied by 1 if above the median or 0 if below the median) and included in the models. sCD14 and LBP levels (above vs. below the median) were strongly associated with GBC [Odds Ratio (95% Confidence Interval): 2.75 (1.27-6.29) for sCD14 and 2.83 (1.32-6.46) for LBP]. The highest vs. lowest tertiles of sCD14 and LBP were associated with a five-fold increased risk of GBC. These associations were attenuated when the inflammation score was entered into the model. Plasma LPS demonstrated a borderline association after adjustment for inflammation score [OR (95% CI): 2.46 (0.96-6.56)]. In contrast, the ORs for inflammation score remained >20 after adjusting for each bacteria-related marker. These findings suggest that bacterial infections may contribute to GBC etiopathogenesis through inflammatory pathways. LPS, sCD14, and LBP and Gallbladder Cancer Relative to Gallstone ControlsLPSSex & Age Adjusted OR (95% CI)Sex, Age, & Inflammation Score Adjusted OR (95% CI)Detectable Level1.001.00Undetectable Level1.81 (0.85-3.80)2.46 (0.96-6.56)sCD14Sex, Age, & Batch Adjusted OR (95% CI)Sex, Age, Batch, & Inflammation Score Adjusted OR (95% CI)Below Median1.001.00Above Median2.75 (1.27-6.29)1.05 (0.39-2.83)1st Tertile1.001.002nd Tertile1.42 (0.45-4.71)0.44 (0.10-1.80)3rd Tertile5.27 (1.98-16.06)1.37 (0.38-5.04)p-trend0.00060.25LBPSex, Age, & Batch Adjusted OR (95% CI)Sex, Age, Batch, & Inflammation Score Adjusted OR (95% CI)Below Median1.001.00Above Median2.83 (1.32-6.46)1.63 (0.64-4.28)1st Tertile1.001.002nd Tertile1.95 (0.61-6.99)1.53 (0.37-7.01)3rd Tertile5.01 (1.84-16.25)2.09 (0.58-8.71)p-trend0.00080.25 Citation Format: Alison L. Van Dyke, Troy J. Kemp, Amanda F. Corbel, Bin Zhu, Yu-Tang Gao, Bingsheng Wang, Asif Rashid, Ming-Chang Shen, Allan Hildesheim, Ann W. Hsing, Ligia A. Pinto, Jill Koshiol. Associations between lipopolysaccharide (LPS) and LPS pathway biomarkers and gallbladder cancer are modulated by markers of systemic inflammation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3441.