• Tuberculosis and Respiratory Diseases
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• v.70 no.6
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• pp.490-497
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• 2011

Background: It is difficult but important to differentiate between bacterial and viral infections, especially for respiratory infections. Hence, there is an ongoing need for sensitive and specific markers of bacterial infections. We investigated novel biomarkers for discriminating community acquired bacterial pneumonia from 2009 H1N1 influenza A infections. Methods: This was a prospective, observational study of patients with community acquired bacterial pneumonia, 2009 H1N1 Influenza A infection, and healthy controls. Serum samples were obtained on the initial visit to the hospital and stored at $-80^{\circ}C$. We evaluated CRP (C-reactive protein), PCT (procalcitonin), LBP (lipopolysaccharide-binding protein) and copeptin. These analytes were all evaluated retrospectively except CRP. Receiver operating characteristic curve (ROC) analyses were performed on the resulting data. Results: Enrolled patients included 27 with community acquired bacterial pneumonia, 20 with 2009 H1N1 Influenza A infection, and 26 who were healthy controls. In an ROC analysis for discriminating community acquired bacterial pneumonia from 2009 H1N1 influenza A infection, areas under the curve (AUCs) were 0.799 for CRP (95% Confidence interval [CI], 0.664~0.934), 0.753 for PCT (95% CI, 0.613~0.892) and 0.684 for LBP (95% CI, 0.531~0.837). Copeptin was not different among the three groups. Conclusion: These findings suggest that serum CRP, PCT and LBP can assist physicians in discriminating community acquired bacterial pneumonia from 2009 H1N1 influenza A infection.

• Journal of Microbiology
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• v.39 no.4
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• pp.314-320
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• 2001

Macrophages stimulated by lipopolysaccharide(LPS) from gram negative bacteria undergo activation of a group of immediate early genes including Rantes. The mouse Rantes gene promoter region contains an LPS rsponsive element(LPE) We detected 3 specific bands termed B1, B2 and 3 formed by the interaction of the LPE and proteins found in LPS-stimulated RAW 367.7 cells. An additional band B4 was determined to be an Ap-1 binding protein. The B1 band appears within 1 hour of LPS nuclear extracts from LPS-stimulation, and this protein kinase enhances B1 and formation. The B1 band can be converted to band B2/B3 by adding specific heparin column fraction purified Ser/Thr specific protein phosphatases PP-1 and PP-2A can stimulate the same conversion to about the same extent. Thus, the formation of the LRE sequence binding complex appears to be regulated by Ser/Thr protein kinase and one or more Ser/Thr specific phosphatases. At least four proteins are involved in the trgulation of the LRE-dependent Rants experssion: two binding factors that bind directly to the target sequences. and two factors that control their binding. The future purification and characterization of these binding pro-teins will reveal in detail the mechanism of Rantes gene activation after LPS stimulation.

• Archives of Pharmacal Research
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• v.18 no.4
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• pp.262-266
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• 1995

Bacterial lipopolysaccharide (LPS) is one of the most potent inducers of various cytokines nad other proinflammatory mediators in macrophages. Although pathophysiological consequences of LPS-induced responses are well established, the mechanisms through which LPS-generated singals are transduced remain unclear. In the present study, we attempted to determine early intracellular events after LPS binding which transduced the signal for the induction of arachidonic acid metabolism in rat alveolar macrophages. While H-7, a protein kinase C(PKC) inhibitor, did not affect LPS-stimulated prostaglandin synthesis, staurosporine enhanced archidonic acid etabolism in macropahages treated with LPS. Phorbol-12-myristate-13 acetate snesitive to LPS compare with control group. PMA and H-7 did not alter the effect of flucose. Pertussis toxin did not show nay effect, thus pertussis toxin snesitive G-protein pathway appears not to play a role in this experimental system. Genistein and tyrphostin 25, protein tyrosine kinase 9PTK) inhibitors, markedly inhibited prostaglandin synthesis in macrophages nal transduction events leading to icnreased macrophage arachidonic acid metabolism.

• Bulletin of the Korean Chemical Society
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• v.35 no.11
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• pp.3169-3174
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• 2014

Numerous studies have examined the role of flavonoids in modulating inflammatory responses in vitro. In this study, we found a novel flavonoid, 3,6,3'-trihydroxyflavone (1), with anti-inflammatory effects. Anti-inflammatory activity and mechanism of action were examined in mouse macrophages stimulated with lipopolysaccharide (LPS). Our results showed that the anti-inflammatory effects of 1 are mediated via p38 mitogen-activated protein kinase (p38 MAPK), Jun-N terminal kinase (JNK), and the extracellular-signal-regulated kinase (ERK) pathway in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Binding studies revealed that 1 had a high binding affinity to JNK1 ($1.568{\times}10^8M^{-1}$) and that the 3- and 6-hydroxyl groups of the C-ring and A-ring of 1 participated in hydrogen bonding interactions with the side chains of Asn114 and Lys55, respectively. The oxygen at the 3' position of the B-ring formed a hydrogen bond with side chain of Met111. Therefore, 1 could be a potential inhibitor of JNKs, with potent anti-inflammatory activity.

• Archives of Pharmacal Research
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• v.26 no.5
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• pp.375-382
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• 2003

Effects of ginsenosides on nitric oxide (NO) production induced by lipopolysaccharide plus TNF-$\alpha$ (LNT) were examined in C6 rat glioma cells. Among several ginsenosides, ginsenoside Rd showed a complete inhibition against LNT-induced NO production. Ginsenoside Rd attenuated LNT-induced increased phosphorylation of ERK. Among several immediate early gene products, only Jun Band Fra-1 protein levels were increased by LNT, and ginsenoside Rd attenuated Jun Band Fra-1 protein levels induced by LNT. Furthermore, LNT increased AP-1 DNA binding activities, which were partially inhibited by ginsenoside Rd. Our results suggest that ginsenoside Rd exerts an inhibitory action against NO production via blocking phosphorylation of ERK, in turn, suppressing immediate early gene products such as Jun Band Fra-1 in C6 glioma cells.

• Clinical and Experimental Pediatrics
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• v.59 no.5
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• pp.231-238
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• 2016

Purpose: Lipopolysaccharide-binding protein (LBP) is a 65-kDa acute phase protein, derived from the liver, which is present in high concentrations in plasma. Data regarding the association between circulating plasma LBP levels and obesity-related biomarkers in the pediatric population are scarce. We aimed to determine whether there was a difference in plasma LBP levels between overweight/obese and normal-weight adolescents and to assess the correlation of circulating LBP levels with anthropometric measures and obesity-related biomarkers, including insulin resistance, liver enzyme levels, and lipid profiles. Methods: The study included 87 adolescents aged 12-13 years; 44 were overweight/obese and 43 were of normal-weight. We assessed anthropometric and laboratory measures, including body mass index (BMI), blood pressure, insulin resistance, liver enzyme levels, and lipid profiles. Plasma LBP levels were measured using an enzyme-linked immunosorbent assay. Results: The mean age of the participants was $12.9{\pm}0.3$ years. Circulating plasma LBP levels were significantly increased in overweight/obese participants compared with those in normal-weight participants ($7.8{\pm}1.9{\mu}g/mL$ vs. $6.0{\pm}1.6{\mu}g/mL$, P<0.001). LBP levels were significantly and positively associated with BMI, systolic blood pressure, aspartate aminotransferase, alanine aminotransferase, total cholesterol, low density lipoprotein-cholesterol, fasting glucose and insulin, and insulin resistance as indicated by the homeostatic model assessment of insulin resistance (HOMA-IR) (all P<0.05). In multivariate linear regression analysis, BMI and HOMA-IR were independently and positively associated with plasma LBP levels. Conclusion: LBP is an inflammatory biomarker associated with BMI and obesity-related insulin resistance in adolescents. The positive correlation between these parameters suggests a potentially relevant pathophysiological mechanism linking LBP to obesity-related insulin resistance in adolescents.

• International Journal of Oral Biology
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• v.42 no.3
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• pp.117-121
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• 2017

We have previously shown that the specific phosphatidylinositol 3-kinase inhibitor LY294002 (LY29), and its inactive analog LY303511 (LY30), inhibit a monocyte chemoattractant protein-1 (MCP-1) expression in human umbilical vein endothelial cells; these results suggest the potential of LY30 as an anti-inflammatory drug. In this study, we determined the effects of LY30 on the production of various inflammatory cytokines in human macrophagic THP-1 cells which were stimulated with lipopolysaccharide (LPS). LY30 selectively suppressed the mRNA expression of IL-12 p40, $TNF-{\alpha}$, and MCP-1 without affecting the expression of $IL-1{\alpha}$, IL-6, and IL-8. Inhibition of the production of IL-12 and $TNF-{\alpha}$ by LY30 was also demonstrated using ELISA assays. In order to elucidate the mechanisms of the action of LY30, we examined the role played by the mitogen-activated protein kinases and the key transcription factors, AP-1 and $NF-{\kappa}B$ in LPS-stimulated THP-1 cells. The results revealed that LY30 inhibited LPS-induced activation of ERK, but not p38 or JNK. Furthermore, the AP-1 DNA binding activity was suppressed by LY30 based upon the dosage, whereas $NF-{\kappa}B$ DNA binding was not affected. These results suggest that LY30 selectively inhibits cytokine production in the LPS-stimulated macrophagic THP-1 cells by down-regulating the activation of ERK and AP-1.

• Journal of Food Hygiene and Safety
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• v.8 no.4
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• pp.181-188
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• 1993

It is well known that bacterial lipopolysaccharide (LPS) stimulates the prostaglandin (PG) synthesis in various experimental system, but the mechanism and the detailed nature of its action are yet to be understood. Thus, this study was designed to characterize LPS induced PG synthesis in rat alveolar macrophage. Although results were not so much prominent, LPS stimulated PGE2 synthesis in macrophage with short term exposure, and this was thought to be mainly due to the activation of phopholipase A2+ But there was a burst in the PG synthesis 6 hours after the LPS treatment and this was accompanied with the increase of cyclooxygenase activity. This effect was not mediated by tumor necrosis factor (TNF) or platelet activating factor (PAF), and the existence of serum was prerequisite for its action. Growth factors such as epidermal growth factor (EGF) and platelet derived growth factor (PDGF) themselves did not stimulate PG synthesis and the showed stimulatory activities to some extent. Normal rat serum was more effective for the elicitation of the LPS action than growth factors. Thus, considering the amounts of growth fafctors contained in normal serum, it was suggested that another factors like LPS binding protein (LBP) might be involved in the serum effect on LPS action. Conclusively. it was thought that LPS could stimulate PG synthesis through interaction with serum factors such as EGF, PDGF and/or LBP.

• Tuberculosis and Respiratory Diseases
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• v.53 no.6
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• pp.595-611
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• 2002

Akt/PKB protein kinase B, ALI acute lung injury, ARDS acute respiratory distress syndrome, CREB C-AMP response element binding protein, ERK extracelluar signal-related kinase, fMLP fMet-Leu-Phe, G-CSF granulocyte colony-stimulating factor, IL interleukin, ILK integrin-linked kinase, JNK Jun N-terminal kinase, LPS lipopolysaccharide, MAP mitogen-activated protein, MEK MAP/ERK kinase, MIP-2 macrophage inflammatory protein-2, MMP matrix metalloproteinase, MPO myeloperoxidase, NADPH nicotinamide adenine dinucleotide phosphate, NE neutrophil elastase, NF-kB nuclear factor-kappa B, NOS nitric oxide synthase, p38 MAPK p38 mitogen activated protein kinase, PAF platelet activating factor, PAKs P21-activated kinases, PMN polymorphonuclear leukocytes, PI3-K phosphatidylinositol 3-kinase, PyK proline-rich tyrosine kinase, ROS reactive oxygen species, TNF-${\alpha}$ tumor necrosis factor-a.

• Journal of fish pathology
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• v.23 no.3
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• pp.323-334
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• 2010

Bactericidal/permeability-increasing protein (BPI) and lipopolysaccharide-binding protein (LBP) are important components of the mammalian innate defence system against Gram-negative infections. The BPI/LBP cDNA was identified from the black rockfish ConA/PMA or LPS stimulated leukocyte cDNA library. The full-length BR-BPI/LBP cDNA was 2118 bp long and contained an open reading frame (ORF) of 1422 bp that encoded 473 amino-acid residues. The 5' UTR had a length of 57 bp, and the 3' UTR 639 bp. The molecular weight and theoretical isoelectric point (pI) values were calculated 51.4 kDa and 9.72, respectively. Compared with other known BPI or BPI/LBP peptide sequences, the most conserved regions of the black rockfish BPI/LBP peptide were found to be the BPI1 N-terminal, BPI2 C-terminal domains and a LPS binding domain. Phylogenetic analysis based on the deduced amino acid sequence revealed a homologous relationship between the BPI/LBP sequence of black rockfish and that of other teleosts. The black rockfish BPI/LBP gene was predominantly expressed in the PBLs, head kidney, trunk kidney and spleen. The expression of the black rockfish BPI/LBP molecule was induced in the peripheral blood leukocytes (PBLs) from 1 to 24 h following LPS stimulation, with a peak at 12 h post-stimulation.