Expression Of Lipopolysaccharide-binding Protein Research Articles

Commensal Bacteria Impact on Intestinal Toll-like Receptor Signaling in Salmonella-Challenged Gnotobiotic Piglets.

Gnotobiotic (GN) animals with simple and defined microbiota can help to elucidate host-pathogen interferences. Hysterectomy-derived germ-free (GF) minipigs were associated at 4 and 24 h post-hysterectomy with porcine commensal mucinolytic Bifidobacterium boum RP36 (RP36) strain or non-mucinolytic strain RP37 (RP37) or at 4 h post-hysterectomy with Lactobacillus amylovorus (LA). One-week-old GN minipigs were infected with Salmonella Typhimurium LT2 strain (LT2). We monitored histological changes in the ileum, mRNA expression of Toll-like receptors (TLRs) 2, 4, and 9 and their related molecules lipopolysaccharide-binding protein (LBP), coreceptors MD-2 and CD14, adaptor proteins MyD88 and TRIF, and receptor for advanced glycation end products (RAGE) in the ileum and colon. LT2 significantly induced expression of TLR2, TLR4, MyD88, LBP, MD-2, and CD14 in the ileum and TLR4, MyD88, TRIF, LBP, and CD14 in the colon. The LT2 infection also significantly increased plasmatic levels of inflammatory markers interleukin (IL)-6 and IL-12/23p40. The previous colonization with RP37 alleviated damage of the ileum caused by the Salmonella infection, and RP37 and LA downregulated plasmatic levels of IL-6. A defined oligo-microbiota composed of bacterial species with selected properties should probably be more effective in downregulating inflammatory response than single bacteria.

Bacterial translocation markers and toll-like receptors in biliary atresia following successful portoenterostomy.

The gut-liver axis may contribute to pathophysiology of cholestatic liver disorders like biliary atresia (BA) by bacterial translocation (BT). Toll-like receptors (TLR) are pattern recognition receptors known to activate innate immunity and secretion of inflammatory cytokines. Herein, we examined BT-associated biomarkers and TLRs in relation to liver injury after successful portoenterostomy (SPE) in BA. Serum levels of lipopolysaccharide-binding protein (LBP), CD14, LAL, TNF-α, IL-6 and FABP2 along with liver expression of TLRs (TLR1, TLR4, TLR7 and TLR9), LBP and CD14 were measured during median 4.9 (1.7-10.6) years follow-up after SPE in 45 BA patients. Serum LBP, CD14, TNF-α and IL-6 all increased after SPE whereas LAL and FABP-2 remained unchanged. Serum LBP correlated positively with CD14 and markers of hepatocyte injury and cholestasis, but not with Metavir fibrosis stage, transcriptional markers for fibrosis (ACTA2) or ductular reaction. Serum CD14 concentration was significantly higher in patients with portal hypertension than without. While liver expression of TLR4 and LBP remained low, TLR7 and TLR1 showed marked BA-specific increases, and TLR7 correlated with Metavir fibrosis stage and ACTA2. BT does not seem to play a significant role in liver injury after SPE in our series of BA patients.

An evolutionary medicine perspective on the cetacean pulmonary immune system — The first identification of SP-D and LBP in the bottlenose dolphin (Tursiops truncatus)

Evolutionary medicine expresses the present status of biomolecules affected by past evolutionary events. To clarify the whole picture of cetacean pneumonia, which is a major threat to cetaceans, their pulmonary immune system should be studied from the perspective of evolutionary medicine. In this in silico study, we focused on cetacean surfactant protein D (SP-D) and lipopolysaccharide-binding protein (LBP) as two representative molecules of the cetacean pulmonary immune system. Sequencing and analyzing SP-D and LBP in the bottlenose dolphin (Tursiops truncatus) lung and liver tissue collected post-mortem elucidated not only basic physicochemical properties but also their evolutionary background. This is the first study to report the sequences and expression of SP-D and LBP in the bottlenose dolphin. Besides, our findings also suggest the direction of an evolutionary arms race in the cetacean pulmonary immune system. These results have important positive implications for cetacean clinical medicine.

Analysis of the Value of Serum Biomarker LBP in the Diagnosis of Spinal Tuberculosis.

ObjectiveTo investigate the correlation between the expression of lipopolysaccharide-binding protein (LBP) in peripheral blood of spinal tuberculosis and clinical diagnosis and to evaluate its value as a diagnostic marker of spinal tuberculosis.MethodsIn the experimental group, clinical history data and peripheral blood were collected from 100 patients with spinal tuberculosis who were admitted to the Department of Spine Surgery, General Hospital of Ningxia Medical University from May 2017 to May 2020, and peripheral blood was collected from 30 healthy volunteers in the control group. Screening of differential LBP expression by proteomics and ELISA to verify its expression in peripheral blood of spinal tuberculosis patients. t-test, Spearman analysis, linear regression and ROC curve were used to evaluate the diagnostic value of LBP in peripheral blood for spinal tuberculosis.ResultsThe expression of LBP protein in peripheral blood is significantly higher in patients with spinal tuberculosis than in the normal population; LBP assay values were significantly and positively correlated with CRP and ESR values (P < 0.01); the AUC of LBP in the diagnosis of spinal tuberculosis for pathological examination, bacteriological culture, T-cell spot test for tuberculosis infection (T-SPOT), imaging diagnosis, and acid fast bacillus were, respectively, 0.677 (P < 0.01), 0.707 (P < 0.01), 0.751 (P < 0.01), 0.714 (P < 0.01), and 0.656 (P < 0.05), and there was a correlation between LBP and the diagnostic evaluation of spinal tuberculosis.ConclusionLBP could be a new candidate biomarker for the diagnosis of spinal tuberculosis.

Metformin Alleviates Neuroinflammation Following Intracerebral Hemorrhage in Mice by Regulating Microglia/Macrophage Phenotype in a Gut Microbiota-Dependent Manner.

The gut microbiota plays a key role in regulating intracerebral hemorrhage (ICH)-induced neuroinflammation. The anti-neuroinflammatory effects of metformin (Met) have been reported in many central nervous system (CNS) diseases. However, whether Met regulates neuroinflammation through the gut microbiota in ICH-induced brain injury remains unknown. We found that Met treatment substantially alleviated neurological dysfunction and reduced neuroinflammation by inhibiting pro-inflammatory polarization of microglia/macrophages in mice with ICH. Moreover, Met treatment altered the microbiota composition and improved intestinal barrier function. The expression of lipopolysaccharide-binding protein (LBP), a biomarker of intestinal barrier damage, was also significantly reduced by Met treatment. Neuroinflammation was also potently ameliorated after the transplantation of fecal microbiota from Met-treated ICH mice. The neuroprotective effects of fecal microbiota transplantation (FMT) were similar to those of oral Met treatment. However, suppression of the gut microbiota negated the neuroprotective effects of Met in ICH mice. Therefore, Met is a promising therapeutic agent for neuroinflammation owing to ICH-induced imbalance of the gut microbiota.

Lipopolysaccharide-binding protein as a biomarker in oral and maxillofacial tumors.

Oral and maxillofacial tumors (OMTs), such as oral squamous cell carcinoma (SCC), pleomorphic adenoma, and ameloblastoma, are common head and neck tumors. Lipopolysaccharide-binding protein (LBP) is a type I acute reactive protein, which participates in body inflammatory response modulation through lipopolysaccharide (LPS)-induced signaling pathway by targeting macrophages (expressing cluster of differentiation 204 [CD204]). Although it is well established that LBP is associated with the development of multiple types of cancer, little is known about the role of LBP in OMTs. This study aims to explore the expression of LBP in OMTs. Here, immunohistochemical (IHC) double staining of LBP and CD204 and enzyme-linked immunosorbent assay (ELISA) were conducted to explore the LBP expression in OMTs. The findings demonstrated that the LBP expression in OMTs was significantly elevated (p<0.001). In addition, the LBP expression was associated with the clinical stage (p<0.001), T classification (p<0.001), and lymph node metastasis (p<0.001, except ELISA) but independent of histological grade of SCC, gender, and age in patients with SCC. The optional cutoff of the LBP serum level is 0.721μg/ml. To conclude, LBP contributes to the development of OMTs and could be a biomarker in the screening and predicting metastasis in patients with OMTs.

Branched-chain amino acids protect the liver from cirrhotic injury via suppression of activation of lipopolysaccharide-binding protein, toll-like receptor 4, and signal transducer and activator of transcription 3, as well as Enterococcus faecalis translocation

ObjectivesBranched-chain amino acids (BCAAs) are used as nutritional support and for improving prognosis in liver cirrhosis. Here we investigate the molecular mechanisms of BCAA treatment and liver damage focused on pathways related to lipopolysaccharide-binding protein (LBP). MethodsSerum LBP levels were measured in cirrhotic patients and in cirrhotic rats treated with BCAA to examine the correlation between liver function and survival. In cirrhotic rats, liver damage, Enterococcus faecalis translocation, serum capsular polysaccharide, and intestinal tight junction levels were assessed. Damaged HepG2 cells were cultured with BCAA-supplemented, BCAA-deficient, or control amino acid medium, followed by examination of LBP expression. ResultsSerum LBP levels were significantly increased in deceased patients individuals with liver cirrhosis. The survival rate in patients with lower serum LBP (<3.48 μg/mL) was significantly improved. In BCAA-treated rat liver samples, protein expression of LBP, toll-like receptor 4 (TLR4), and phosphorylated signal transduction and activator of transcription 3 (STAT3) were significantly reduced. Also in BCAA-treated rats, intestinal zonula occludens gene expression was increased, whereas hepatic translocation of E. faecalis and serum capsular polysaccharide levels were reduced. In damaged HepG2 cells, lipopolysaccharide-induced elevation of LBP expression was rapidly and strongly repressed in BCAA-enriched medium. ConclusionsSerum LBP level is a prognostic biomarker in liver cirrhosis. BCAA treatment reduced translocation of E. faecalis through intestinal tight junction recovery and reduced LBP expression in the liver, which repressed activation of LBP, toll-like receptor 4, and signal transduction and activator of transcription 3. Our findings suggest that BCAA supplementation protects the liver from damage via multiple pathways.

The level of lipopolysaccharide-binding protein in acute intestinal infections, the effect of IL-1β and IL-10 on its production

Aim. To determine the level of lipopolysaccharide-binding protein (LBP) in acute intestinal infection, depending on the etiology and severity of the disease, and the effect of interleukin (IL)-1 and IL-10 levels on the expression of LBP.&#x0D; Methods. Serum samples of 62 patients were assayed by solid phase enzyme-linked immunosorbent assay using a set of reagents ELISA (USA) and Vector-best (Novosibirsk) for levels of LBР, IL-1, IL-10. The first group included 33 patients with bacterial intestinal infection, the second group consisted of 29 patients with viral diarrhea, and the control group comprised 20 conditionally healthy patients. Analyses were performed using Microsoft Excel 2010 and Statistica version 6.0 software. Statistical differences were determined by using the MannWhitney U Test, the p-value 0.05 were regarded as statistically significant. Spearmans correlation coefficient was used to examine relationships. ShapiroWilk W test was used to check for normal distribution of the features.&#x0D; Results. We detected the presence of LBP in all the studied groups, with the content of LBP was significantly increased in the group of bacterial intestinal infections compared with other groups. With regard to disease severity, LBP level was the highest for mild acute intestinal infections caused by bacteria, and for viral diarrhea, fluctuations in LBP did not exceed the norm. In intestinal infections caused by bacteria, the levels of LBP were directly related to the levels of IL-1 and IL-10.&#x0D; Conclusion. Detection of LBP concentration can be used for the initial differential diagnosis of intestinal infections caused by bacteria, which would significantly narrow the diagnostic search and determine the tactics of etiotropic therapy; also, considering the relationship between the concentration of LBP and disease severity, this indicator can be used as a predictive sign of the course of the disease.

Identification of Aberrantly Methylated Differentially CpG Sites in Hepatocellular Carcinoma and Their Association With Patient Survival

This study aimed to identify aberrantly methylated differentially methylated CpG sites (DMCs) and investigate their prognostic value in hepatocellular carcinoma (HCC). A total of 2,404 DMCs were selected from Gene Expression Omnibus (GEO) and validated by The Cancer Genome Atlas (TCGA). The TCGA cohort was divided into a training cohort and a validating cohort. First, the prognostic model based on six DMCs, including cg08351331, cg02910574, cg09947274, cg17589341, cg24652919, and cg26545968, was constructed based on the least absolute shrinkage and selection operator (LASSO) regression Cox analysis. The area under the curve (AUC) of the DMC-based model was 0.765 in the training cohort and 0.734 in the validating cohort. The accuracy of a model combining the DMC signature and American Joint Committee on Cancer (AJCC) stage, with an AUC of 0.795, was better than that of the DMCs or AJCC stage alone. Second, further analysis revealed that the methylation rate of cg08351331 was negatively associated with the expression of its relative gene, lipopolysaccharide-binding protein (LBP). Besides, the gene expression of LBP was significantly associated with poor overall survival in patients with hepatitis B virus (HBV) infection. Finally, these findings were confirmed by GSE57956 data and our own cohort. In conclusion, we established an accurate DMC-based prognostic model that could be combined with AJCC stage to improve the accuracy of prognostic prediction in HCC. Moreover, our preliminary data indicate that LBP may be a new key factor in HBV-induced HCC initiation through the regulation of its methylation.

Tissue-specific expression and correlation with promoter DNA methylation of the LBP gene in pigs

Lipopolysaccharide binding protein (LBP) is a key factor in the recognition of lipopolysaccharide (LPS) and the initiation of immune response, thus regulating the body's resistance to pathogenic infection. To investigate the tissue-specific expression characteristics of the LBP gene and its transcriptional regulation in pigs, we detected LBP expression in different tissues of 35-day-old Meishan weaned piglets, determined LBP core promoter region using bioinformatics prediction combined with dual luciferase activity assay, and finally detected methylation levels by pyrosequencing. The results showed that LBP expression in the liver tissue was significantly higher (P>0.01) than that in other tissues, followed by the intestinal tissues. The core promoter region of LBP was located at –500–(–206) bp (chr.17: g.46837534–g.46837828), containing three CpG sites (CpG1, CpG2 and CpG3). Of the three CpG sites, CpG2 and CpG3 were variously methylated (P>0.01) in different tissues. Moreover, LBP mRNA levels were negatively correlated (P>0.01) with methylation levels of the CpG2 and CpG3 sites in the YY1 transcription factor binding sequence. It is speculated that the methylation of CpG2 and CpG3 sites might inhibit YY1 binding to the promoter sequences, thereby regulating the tissue-specific expression of LBP. This study demonstrated the distinct patterns of LBP expression and promoter methylation in the tissues of Meishan pigs and indicated the potential roles of DNA methylation in regulating LBP expression, which may contribute to further investigations on pig LBP gene expression and function.

Association of decreased levels of lipopolysaccharide-binding protein with OKN-007-induced regression of tumor growth in an F98 rat glioma model.

High-grade gliomas, such as glioblastoma (GBM), are devastating tumors with a very poor prognosis. Previously the authors have found that the nitrone compound OKN-007 (OKlahoma Nitrone 007; or disodium 4-[(tert-butyl-imino) methyl] benzene-1,3-disulfonate N-oxide) is effective against high-grade gliomas in various GBM rodent and human xenograft models. The purpose of the present study was to assess the levels of the lipopolysaccharide-binding protein (LBP) in rodent gliomas treated with OKN-007 as well as determine the expression of LBP in human gliomas. Microarray analysis was done to assess altered gene expression following OKN-007 administration in an F98 glioma model. An enzyme-linked immunosorbent assay was incorporated to assess LBP levels in glioma tissues, as well as blood serum, comparing results in OKN-007-treated and untreated tumor-bearing animals. Immunohistochemistry was used to assess LBP levels in varying grades of human glioma tissue sections. Upon further assessment of gene expression fold changes in F98 gliomas in rats that received or did not receive OKN-007, it was found that the gene for LBP was significantly downregulated by OKN-007. Further investigation was done to see whether levels of LBP were affected by OKN-007 treatment in F98 gliomas. It was found that LBP could be detected not only in glioma tissue but also in blood serum of F98 glioma-bearing rats and that OKN-007 decreased the levels of LBP. It was also found that LBP levels are highly expressed in human high-grade glioma tissues. LBP could potentially be used as a serum diagnostic marker of treatment response in high-grade gliomas.

Expression of inflammatory lipopolysaccharide binding protein (LBP) predicts the progression of conventional renal cell carcinoma - a short report.

The mortality of conventional renal cell carcinoma (RCC) correlates directly with the presence or postoperative development of metastases. The aim of this study was to identify new markers associated with the postoperative progression of conventional RCC. Tissue microarrays (TMA) of conventional RCC from a cohort of 414 patients were analysed by immunohistochemistry for expression of the lipopolysaccharide binding protein (LBP), which was identified as a candidate biomarker through Affymetrix U133 Plus 2.0 array analysis. Univariate and multivariate Cox regression models were addressed to cancer-specific survival in association with age, sex, clinicopathological parameters and LBP expression. The survival time of the patients was estimated by Kaplan-Meier analyses, and comparisons of survival curves were made using the Log rank test. Univariate analysis revealed an association of patient survival with all clinicopathological parameters tested and LBP expression. In multivariate analysis only T classification, grade and LBP staining showed a significant association with postoperative cancer-specific survival (p<0.001). LBP expression was found to be associated with a poor patient survival in Kaplan-Meier analyses. The estimated median survival time for patients with tumours showing LBP expression was 74months, whereas the overall survival time was 142months. LBP expression in conventional RCC defines a group of patients at a high risk of postoperative progression and may help to direct optimized active surveillance and timely adjuvant therapy.

Oxymatrine protects against sepsis-induced myocardial injury via inhibition of the TNF-α/p38-MAPK/caspase-3 signaling pathway.

Oxymatrine (OMT), which is a quinolizidine alkaloid extracted from the traditional Chinese herb Sophoraflavescens Aiton, is often used to treat various inflammatory diseases. The present study aimed to investigate the protective effects of OMT against septic shock‑induced myocardial injury in rats, and to determine the underlying mechanisms. In the present study, cecal ligation and puncture (CLP) was applied to generate a rat model of sepsis. The rats were randomly divided into six groups (n=8/group): Sham operation (CON) group, OMT control group, CLP model group, and CLP+OMT (high dose, 52mg/kg; medium dose, 26mg/kg; low dose, 13mg/kg) groups. Cardiac function and histological alterations were analyzed by light microscopy and electron microscopy. Myocardial cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The mRNA and protein expression levels were examined by reverse transcription-polymerase chain reaction and western blotting, respectively. Furthermore, the levels of tumor necrosis factor (TNF)‑α in the myocardial tissue were determined by radioimmunoassay. The results demonstrated that OMT exhibited anti‑inflammatory properties, improved myocardial contractility and compliance, and significantly decreased pathological injury to rat myocardial ultrastructure. In addition, OMT significantly decreased heart rate and left ventricular end diastolic pressure, and increased mean arterial pressure, left intraventricular pressure change rate, and left ventricular end systolic pressure in rats following septic shock. Treatment with OMT attenuated the mRNA expression of lipopolysaccharide binding protein, cluster of differentiation14, nuclear factor (NF)‑κB (p65), TNF‑α, p38‑mitogen‑activated protein kinase (MAPK) and caspase‑3, and decreased the protein expression of NF‑κB (p65), phosphorylated (p)NF‑κB inhibitor‑α, p‑p38‑MAPK caspase‑3 and TNF‑α in septic myocardial tissue. The present study concluded that OMT may offer substantial therapeutic potential for the treatment of septic shock‑induced myocardial injury by inhibiting the TNF-α/p38-MAPK/caspase-3 signaling pathway.

Expression of α1-acid glycoprotein and lipopolysaccharide binding protein in visceral and subcutaneous adipose tissue of dairy cattle

Adipose tissue is an endocrine compartment that plays an important role in immune defence by producing and releasing a wide range of proteins, including acute phase proteins (APPs). The liver is the main organ of APP synthesis, although extrahepatic production has also been reported. In the present study, expression of two APPs in dairy cattle, lipopolysaccharide binding protein (LBP) and α1-acid glycoprotein (AGP), was determined in four visceral (pericardial, mesenteric, omental and retroperitoneal) and three subcutaneous (withers, tail head and sternum) adipose tissue depots. mRNA expression was evaluated using qualitative and quantitative PCR, protein profiles were assessed by Western blot analysis and cellular localisation was determined by immunohistochemistry. The presence of LBP and AGP was demonstrated at mRNA and protein levels in all seven adipose tissue depots. Expression of AGP and LBP suggests that they may have roles as local and systemic inflammatory adipokines.

The Kinetic Expression of Lipopolysaccharide-Binding Protein and CD14 Gene in Obstructive Jaundice

ABSTRACTBackground: Binding lipopolysaccharide (LPS) with high-affinity, lipopolysaccharide-binding protein (LBP) and CD14 lower the threshold stimulatory concentrations of LPS dramatically and enhance the rate of cytokine production markedly. This study aimed to investigate the kinetic expression of LBP/CD14 and its possible relationship with tumor necrosis factor alpha (TNF-α) to better understand the pathophysiology of obstructive jaundice. Materials and Methods: The tissues (liver, spleen, intestine, and lung) of male Sprague-Dawley rats were harvested at pre-bile duct ligation in controls and at specific time points (24, 48, 72, 96, and 120 hr) after bile duct ligation. LBP, CD14, and TNF-α mRNA expression were measured in tissues harvested from controls and at the specific time points. Results: Hepatic LBP mRNA expression increased significantly at five days after bile duct ligation. CD 14 mRNA expression increased significantly after five days of bile duct ligation in liver, lung, spleen, and ileum. TNF-α mRNA expression increased significantly in all four organs (liver, lung, spleen, and ileum) after four days of bile duct ligation. Conclusion: Five days of bile duct ligation upregulated CD 14 mRNA expression in liver, lung, spleen, and ileum and increased TNF-α mRNA expression simultaneously in the liver, lung, spleen, and ileum. In addition, five days of bile duct ligation also upregulated LBP mRNA expression in the liver and increased hepatic TNF-α mRNA expression simultaneously. The kinetic expressions of LBP and CD 14 in obstructive jaundice are intriguing and further evaluation is warranted.

Impact of Intramammary Treatment on Gene Expression Profiles in Bovine Escherichia coli Mastitis

Clinical mastitis caused by E. coli accounts for significant production losses and animal welfare concerns on dairy farms worldwide. The benefits of therapeutic intervention in mild to moderate cases are incompletely understood. We investigated the effect of intramammary treatment with cefapirin alone or in combination with prednisolone on gene expression profiles in experimentally-induced E. coli mastitis in six mid-lactating Holstein Friesian cows. Cows were challenged with E. coli in 3 quarters and received 4 doses of 300 mg cefapirin in one quarter and 4 doses of 300 mg cefapirin together with 20 mg prednisolone in another quarter. At 24 h (n = 3) or 48 h (n = 3) post-challenge, tissue samples from control and treated quarters were collected for microarray analysis. Gene expression analysis of challenged, un-treated quarters revealed an up-regulation of transcripts associated with immune response functions compared to un-challenged quarters. Both treatments resulted in down-regulation of these transcripts compared to challenged, un-treated quarters most prominently for genes representing Chemokine and TLR-signaling pathways. Gene expression of Lipopolysaccharide Binding Protein (LBP), CCL2 and CXCL2 were only significantly down-regulated in cefapirin-prednisolone-treated quarters compared to un-treated controls. Down-regulation of chemokines was further confirmed on the basis of protein levels in milk whey for CXCL1, CXCL2 and CXCL8 in both treatments with a greater decrease in cefapirin-prednisolone-treated quarters. The data reveal a significant effect of treatment on cell recruitment with a more pronounced effect in cefapirin-prednisolone treated quarters. Provided a rapid bacteriological clearance, combination therapy may prevent neutrophil-induced tissue damage and promote recovery of the gland.

Lipopolysaccharide-binding protein is increased in patients with psoriasis with metabolic syndrome, and correlates with C-reactive protein

Lipopolysaccharide-binding protein (LBP) is a reliable indicator of serum lipopolysaccharide (LPS) concentration. Raised levels of circulating LPS can trigger an increase in chronic pro-inflammatory cytokines, which may mediate the development of insulin resistance and obesity. Psoriasis is a chronic inflammatory skin disease that has been associated with metabolic syndrome. We aimed to study the expression of LBP in patients with psoriasis treated with narrowband ultraviolet B phototherapy, and controls matched by age, gender and body mass index (BMI). We did not find any differences in serum LBP concentration between patients and controls, and serum LBP did not correlate with the Psoriasis Area and Severity Index. However, patients with psoriasis and metabolic syndrome had higher serum concentration of LBP than controls. Furthermore, correlation with BMI and apolipoprotein B was present in controls, but not in patients with psoriasis. Serum LBP level did not change significantly after treatment with phototherapy.

Early Life Stress Inhibits Expression of a Novel Innate Immune Pathway in the Developing Hippocampus

Childhood maltreatment represents a major risk factor for the development of numerous childhood psychopathologies that in many cases linger as chronic mental illnesses in adulthood. Exposing rodents or non-human primates to early life stress increases anxiety-like behaviors and impairs cognitive function in adulthood, suggesting that animal models may provide important insights into parallel developmental processes in humans. Using an unbiased genomic screen, we found that expression of lipopolysaccharide binding protein (LBP), a member of the innate immune system, is dramatically decreased in the hippocampus of pups exposed to early life stress. LBP levels peak in the normally developing hippocampus at a period of intense synaptic pruning, during which LBP is colocalized with the synaptic marker PSD95 and is found in close proximity to processes of microglia cells. Expression of LBP declines to low levels seen in adulthood at around postnatal day 30. Importantly, 30-day-old LBP knockout (k.o.) mice show increased spine density and abnormal spine morphology, suggesting that peak levels of LBP during the second and third weeks of life are necessary for normal synaptic pruning in the hippocampus. Finally, LBP k.o. mice show impaired hippocampal-dependent memory and increased anxiety-like behaviors in a manner that resembles that seen in animals exposed to early life stress. These findings describe a novel role for LBP in normal hippocampal development and raise the possibility that at least some of the behavioral sequelae of early life stress are mediated by reduced expression of LBP during a critical period of neurodevelopment.

Anti-inflammatory properties of Ajuga bracteosa in vivo and in vitro study and their effects on mouse model of liver fibrosis

The entire plant of Ajuga bracteosa Wall has been used to treat various inflammatory disorders, including hepatitis, in Taiwan. This study evaluated the hepatoprotective ability of Ajuga bracteosa extract (ABE). We investigated the inhibitory action of a chloroform fraction of ABE (ABCE) on lipopolysaccharide (LPS)-stimulated RAW264.7 cells and Kupffer cells. Hepatic fibrosis was induced in mice through the administration of CCl(4) twice a week for 8 weeks. Mice in three CCl(4) groups were treated daily with water and ABE throughout the duration of the experiment. In LPS-stimulated RAW264.7 cells and Kupffer cells, ABCE inhibited the production of NO and/or TNF-α and also blocked the LPS-induced expression of NO synthase. ABCE inhibited the activation of NF-κB induced by LPS, associated with the abrogation of IκBα degradation, with a subsequent decrease in nuclear p65 and p50 protein levels. The phosphorylation of MAPKs in LPS-stimulated RAW264.7 cells was also suppressed using ABCE. In the in vivo study, ABE protected the liver from injury by reducing the activity of plasma aminotransferase, and by improving the histological architecture of the liver. RT-PCR analysis showed that ABE inhibited the hepatic mRNA expression of LPS binding protein, CD14, TNF-α, collagen(α1)(I), and α-smooth actin. These results indicate that ABE alleviated CCl(4)-induced liver fibrosis, and that this protection is probably due to the suppression of macrophage activation.

Hepatocytes express functional NOD1 and NOD2 receptors: A role for NOD1 in hepatocyte CC and CXC chemokine production

NOD-like receptors are recently described cytosolic pattern recognition receptors. NOD1 and NOD2 are members of this family that recognize bacterial cell wall components, diaminopimelic acid and muramyl dipeptide, respectively. Both NOD1 and NOD2 have been associated with many inflammatory diseases, although their role in liver inflammation and infection has not been well studied. We investigated the role of NOD receptors in mouse liver by assessing expression and activation of NOD1 and NOD2 in liver and primary isolated hepatocytes from C57BL/6 mice. Both NOD1 and NOD2 mRNA and protein were highly expressed in hepatocytes and liver. RIP2, the main signaling partner for NODs, was also expressed. Stimulation of hepatocytes with NOD1 ligand (C12-iEDAP) induced NFkappaB activation, activation of MAP kinases and expression of chemokines CCL5 (RANTES) and CXCL1 (KC). C12-iEDAP also synergized with interferon (IFN)gamma to increase iNOS expression and production of nitric oxide. Despite activating NFkappaB, NOD1 ligand did not upregulate hepatocyte production of the acute phase proteins lipopolysaccharide binding protein, serum amyloid A, or soluble CD14 in cell culture supernatants, or upregulate mRNA expression of lipopolysaccharide binding protein, serum amyloid A, C-reactive protein, or serum amyloid P. NOD2 ligand (MDP) did not activate hepatocytes when given alone, but did synergize with Toll-like receptor ligands, lipopolysaccharide (LPS), and polyI:C to activate NFkappaB and MAPK. All together these data suggest an important role for hepatocyte NOD1 in attracting leukocytes to the liver during infection and for hepatic NLRs to augment innate immune responses to pathogens.