Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study, we characterized a model system in which we examined the effects of human surfactant protein A (SP-A) on the uptake of a common human pulmonary pathogen, Pseudomonas aeruginosa, by a human monocytic/macrophage cell line, THP-1 cells. We found that SP-A significantly increases uptake of the bacteria in a dose-dependent manner. Bacterial uptake was temperature-dependent, because an effect of SP-A on bacterial uptake was observed at 37 degrees C and not at 4 degrees C. The continued presence of SP-A during the period when the bacteria and THP-1 cells were co-incubated was necessary for enhanced uptake. Pre-incubation of the bacteria or THP-1 cells with SP-A, followed by washing, abolished the effect of SP-A on bacterial uptake. The effect of SP-A could be inhibited by high concentrations of mannose, but was not affected by the removal or addition of lipopolysaccharide (LPS). Finally, we observed that the SP-A-mediated increase in uptake of P. aeruginosa by THP-1 cells was optimal in a narrow (100 mM and 150 mM) range of NaCl concentrations. We conclude that SP-A enhances the THP-1 cell-mediated uptake of P. aeruginosa in a manner dependent on temperature, the concentration of SP-A, and the concentration of NaCl.
Am J Respir Cell Mol Biol 2001 Dec
PMID:Effects of surfactant protein A and NaCl concentration on the uptake of Pseudomonas aeruginosa by THP-1 cells. 1172 90

Mycobacterium tuberculosis (Mtb) infection induces the expression of matrix metalloproteinase-9 (MMP-9) in mouse lungs. In cultured human monocytic cells, Mtb bacilli and the cell wall glycolipid lipoarabinomannan (LAM) stimulate high levels of MMP-9 activity. Here, we explore the cellular mechanisms involved in the induction of MMP-9 by Mtb. We show that infection of THP-1 cells with Mtb caused a fivefold increase in MMP-9 mRNA that was associated with increased MMP-9 activity. MMP-9 induction was dependent on microtubule polymerization and protein kinase activation and was associated with increased DNA binding by the transcription factor activator protein-1 (AP-1), which appeared to be important for MMP-9 expression. We then explored the surface molecules potentially involved in Mtb induction of MMP-9, focusing on ligands of the mannose and beta-glucan receptors. MMP-9 activity was induced by the mannose receptor ligands mannan, zymosan, and LAM, whereas the beta-glucan receptor ligand laminarin was not effective. The most active inducers of MMP-9 activity were the particulate ligand zymosan and LAM. Pretreatment of cells with an anti-mannose receptor monoclonal antibody, but not anti-complement receptor 3, decreased the induction of MMP-9 activity by Mtb bacilli. Together, these results suggest that MMP-9 induction by Mtb occurs by receptor-mediated signaling mechanisms involving the binding of mannosylated ligands to mannose receptors, the modulation by cytoskeletal elements such as microtubules, the activation of protein kinases, and transcriptional activation by AP-1.
Am J Physiol Lung Cell Mol Physiol 2002 Mar
PMID:M. tuberculosis induction of matrix metalloproteinase-9: the role of mannose and receptor-mediated mechanisms. 1183 51

Thioredoxin (TRX) and glutathione (GSH) are key regulators of the cellular balance of reduction/oxidation (redox). The impaired redox balance in joint cellular circumstances participates in immune dysfunctions seen in patients with rheumatoid arthritis (RA). We analyzed effects of a newly developed anti-rheumatic drug, KE-298 (2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid) and it is active metabolite; KE-758 (2-mercaptomethyl-4-(4-methylphenyl)-4-oxobutanoic acid) on the secretion of TRX and the level of intracellular GSH in THP-1 cells, a human monocytic cell line and in Jurkat cells, a human T cell leukemia cell line, then we compared their effects with N-acetyl-L-cysteine (NAC). KE-298 (10-100 microg/ml) and KE-758 (10-100 microg/ml) as well as a high concentration of NAC (10mM) dose-dependently inhibited the secretion of TRX by THP-1 and Jurkat cells. RT-PCR analysis indicated that the suppressive effects of KE-298 and KE-758 on TRX secretion could be partly explained by the inhibition of TRX mRNA expression. On the other hand, KE-758 as well as a high concentration of NAC significantly increased the level of intracellular GSH. Thus, KE-298 is a novel sulphydryl drug which regulates the redox state of cellular circumstances. The potential of KE-298 to suppress the secretion of TRX and to increase the level of intracellular GSH may partly explain the efficacy in cases of RA.
Mol Immunol 2002 Feb
PMID:Effects of a new anti-rheumatic drug KE-298 and its active metabolite: KE-758 on secretion of thioredoxin and on the level of intracellular glutathione in human monocytes and T cells. 1184 39

Fetal human osteoblast-like cells and the THP-1 cell line that differentiates into macrophage/osteoblast-like cells in the presence of Vitamin D3 and which possesses high aromatase activity, constitute a useful model with which to study the regulation of aromatase in bone. We showed that dexamethasone (DEX)-induced aromatase activity in the THP-1 cell line is completely suppressed by forskolin and by dibutyryl cAMP. We therefore investigated the contribution of mitogen-activated protein kinase (MAPK) to the regulation of aromatase, because cAMP inhibits MAPK in many cells. We examined the role of MAPK on aromatase activity using PD98059, a selective inhibitor of MEK-1. PD98059 (100 microM) reduced DEX+interleukin (IL)-1beta-induced aromatase activity in human osteoblast-like cells by more than 90%, whereas 50% of the aromatase mRNA concentration was retained compared with the control incubated with DEX+IL-1beta. PD98059 (50 microM) reduced the activity of aromatase in THP-1 cells by 80% without significantly affecting the mRNA level. These results indicated that MAPK plays an important role in aromatase activation at the post-transcriptional level.
J Steroid Biochem Mol Biol 2001 Dec
PMID:Regulation of aromatase activity in bone-derived cells: possible role of mitogen-activated protein kinase. 1185 Feb 8

17alpha-methyl testosterone is a synthetic androgen with affinity for the androgen receptor. 17alpha-methyl testosterone is used widely as a component of hormone replacement therapy. Previous reports have indicated that contrary to testosterone, 17alpha-methyl testosterone is not aromatized. However, 17alpha-methyl testosterone still could affect local estrogen formation by regulating aromatase expression or by inhibiting aromatase action. Both possibilities have important clinical implications. To evaluate the effect of 17alpha-methyl testosterone on the expression and activity of aromatase, we tested the choriocarcinoma Jar cell line, a cell line that express high levels of P450 aromatase, and the macrophage-like THP-1 cells, which express aromatase only after undergoing differentiation. We found that in both cell lines, 17alpha-methyl testosterone inhibits aromatase activity in a dose-related manner. The curve of inhibition parallels that of letrozole and gives complete inhibition at 10(-4) M 17alpha-methyl testosterone, determined by the tritium release assay. 17alpha-methyl testosterone does not have detectable effects on aromatase RNA and protein expression by Jar cells. Undifferentiated THP-1 cells had no aromatase activity and showed no effect of 17alpha-methyl testosterone, but differentiated THP-1 (macrophage-like) cells had a similar inhibition of aromatase activity by 17alpha-methyl testosterone to that seen in Jar cells. The Lineweaver-Burke plot shows 17alpha-methyl testosterone to be a competitive aromatase inhibitor. Our results show for the first time that 17alpha-methyl testosterone acts as an aromatase inhibitor. These findings are relevant for understanding the effects of 17alpha-methyl testosterone as a component of hormone replacement therapy. 17alpha-methyl testosterone may, as a functional androgen and orally active steroidal inhibitor of endogenous estrogen production, also offer special possibilities for the prevention/treatment of hormone-sensitive cancers.
J Steroid Biochem Mol Biol 2001 Dec
PMID:17alpha-methyl testosterone is a competitive inhibitor of aromatase activity in Jar choriocarcinoma cells and macrophage-like THP-1 cells in culture. 1185 Feb 30

Amyloid-beta protein (A beta) is known to induce microglial activation with concomitant release of cytokines. Gangliosides have documented neuritogenic and neurotrophic properties. We determined the effects of A beta on the release of interleukin-1beta (IL-1beta) from the human monocytic cell line, THP-1 cells. A beta 1-42 significantly induced the release of IL-1beta from the cells. A beta 1-40, A beta 40-1, A beta 1-38, and A beta precursor protein (beta-APP) analogs also released a small amount of IL-1beta. A beta 1-42-activated cells demonstrated approx an 18-fold higher IL-1beta release than that for control cells or A beta 1-40 (soluble; S) treated cells. The release of IL-1beta from A beta 1-42-activated cells was significantly inhibited (33-48% of activated cells; p < 0.05 for the control value) by addition of gangliosides, suggesting that gangliosides inhibit the continuous cycle of the IL-1beta production in THP-1 cells.
J Mol Neurosci 2001 Dec
PMID:Gangliosides inhibit the release of interleukin-1beta in amyloid beta-protein-treated human monocytic cells. 1185 33

Fetal membrane rupture is associated with increased expression of matrix metalloproteinase-9 (MMP-9) and matrix degradation. We have determined the functional significance of a variable number tandem repeat and a single nucleotide polymorphism (SNP) in the MMP-9 gene on promoter activity and their association with preterm premature rupture of membranes (PPROM). The 14 CA-repeat allele was a stronger promoter than the 20 CA-repeat allele in amnion epithelial cells and WISH amnion-derived cells, but in THP-1 monocyte/macrophage cells the 14 and 20 CA-repeat alleles had similar activities. An SNP at -1562 did not significantly affect promoter activity. A case-control study of African American neonates revealed that the 14 CA-repeat allele was more common in newborns delivered of mothers who had PPROM than in those delivered at term. There was no association between the -1562 SNP and PPROM. We conclude that there are cell host-dependent differences in MMP-9 promoter activity related to CA-repeat number and that fetal carriage of the 14 CA-repeat allele is associated with PPROM in African Americans.
Mol Hum Reprod 2002 May
PMID:A polymorphism in the matrix metalloproteinase-9 promoter is associated with increased risk of preterm premature rupture of membranes in African Americans. 1199 47

Extracts of plants have been widely evaluated for possible antiproliferative and anticarcinogenic properties. The antiproliferative activity of ethanolic extract of Boerhaavia diffusa, a plant used in traditional medicine, was evaluated in several cells. It inhibited T cell mitogen phytohemagglutinin and concanavalin A-stimulated proliferation of human peripheral blood mononuclear cells (PBMC). It also inhibited purified protein derivative antigen-stimulated PBMC proliferation and human mixed lymphocyte culture. In addition, B. diffusa extract inhibited the growth of several cell lines of mouse and human origin, such as mouse macrophage cells (RAW 264.7), human macrophage cells (U937), human monocytic cells (THP-1), mouse fibroblast cells (L929), human embryonic kidney cells (HEK293), mouse liver cells (BNLCL.2), African green monkey kidney cells (COS-1), mouse lymphoma cells (EL-4), human erythroleukemic cells (K562), and human T cells (Jurkat). The present study has demonstrated the antiproliferative potential of ethanolic extract of B. diffusa in vitro.
Exp Mol Pathol 2002 Jun
PMID:Antilymphoproliferative activity of ethanolic extract of Boerhaavia diffusa roots. 1200 88

We identified Mycobacterium tuberculosis genes preferentially expressed during infection of human macrophages using a promoter trap adapted for this pathogen. inhA encodes an enoyl-acyl carrier protein reductase that is required for mycolic acid biosynthesis (A. Quemard et al., Biochemistry 34:8235-8241, 1995) and is a major target for isoniazid (INH) in mycobacterial species (A. Banerjee et al., Science 263:227-230, 1994). Since overexpression of inhA confers INH resistance in Mycobacterium smegmatis (Banerjee et al., Science 263:227-230, 1994), we designed a promoter trap based on this gene. A library of clones, containing small fragments of M. tuberculosis DNA cloned upstream of inhA in a plasmid vector, was electroporated into M. tuberculosis, and the resulting culture was used to infect the human monocytic THP-1 cell line. Selection was made for clones surviving INH treatment during infection but retaining INH sensitivity on plates. The DNA upstream of inhA was sequenced in each clone to identify the promoter driving inhA expression. Thirteen genes identified by this method were analyzed by quantitative reverse transcription-PCR (R. Manganelli et al., Mol. Microbiol. 31:715-724, 1999), and eight of them were found to be differentially expressed from cultures grown in macrophages compared with broth-grown cultures. Several of these genes are presumed to be involved in fatty acid metabolism; one potentially codes for a unique DNA binding protein, one codes for a possible potassium channel protein, and the others code for proteins of unknown function. Genes which are induced during infection are likely to be significant for survival and growth of the pathogen; our results lend support to the view that fatty acid metabolism is essential for the virulence of M. tuberculosis.
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PMID:Mycobacterium tuberculosis genes induced during infection of human macrophages. 1201 Sep 64

Surfactant protein A (SP-A) plays a role in host defense and inflammation in the lung. In the present study, we investigated the hypothesis that SP-A is involved in bleomycin-induced pulmonary fibrosis. We studied the effects of human SP-A on bleomycin-induced cytokine production and mRNA expression in THP-1 macrophage-like cells and obtained the following results. 1) Bleomycin-treated THP-1 cells increased tumor necrosis factor (TNF)-alpha, interleukin (IL)-8, and IL-1beta production in dose- and time-dependent patterns, as we have observed with SP-A. TNF-alpha levels were unaffected by treatment with cytosine arabinoside. 2) The combined bleomycin-SP-A effect on cytokine production is additive by RNase protection assay and synergistic by enzyme-linked immunosorbent assay. 3) Although the bleomycin effect on cytokine production was not significantly affected by the presence of surfactant lipid, the additive and synergistic effect of SP-A-bleomycin on cytokine production was significantly reduced. We speculate that the elevated cytokine levels resulting from the bleomycin-SP-A synergism are responsible for bleomycin-induced pulmonary fibrosis and that surfactant lipids can help ameliorate pulmonary complications observed during bleomycin chemotherapy.
Am J Physiol Lung Cell Mol Physiol 2002 Jul
PMID:Combined SP-A-bleomycin effect on cytokines by THP-1 cells: impact of surfactant lipids on this effect. 1206 May 65


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