Biomedical subjects

J J Jones

Publications and source records attributed to J J Jones.

At least 19 recordsLinked to original sources

PubMed2001

A method for identification of inhibitors of the phosphorylation reactions of bacterial response regulator proteins using (31)P nuclear magnetic resonance spectroscopy.

Bacterial response regulators are attractive targets for antibacterial drug development, yet random screening against these targets has failed as yet to identify chemicals that constitute viable leads. Alternative methods to provide leads for drug development based on identification and optimization of low affinity ligands from NMR screens have been described. However, leads from these processes still require verification in a bioassay, which is often problematic if compounds have unfavorable optical and solubility properties. A simple method, based on using NMR to observe the activity of the target, is described. It has the advantages of being able to characterize both low affinity leads and a wider selection of compounds in a structure activity relationships series, without the problems affecting a fluorescence assay. In this example we use (31)P to monitor the turnover of a bacterial response regulator, but the generic approach could be applied to other nuclei and thus a range of biological systems.

Anti-Bacterial Agents↗

PubMed2001

Calcium buffering in coronary smooth muscle after chronic occlusion and exercise training.

OBJECTIVE: Exercise promotes "sarcoplasmic reticulum (SR) Ca2+ unloading" in porcine coronary smooth muscle, resulting in decreased agonist-induced Ca2+ release. We studied Ca2+ handling in healthy, non-occluded right coronary artery cells from hearts chronically occluded at the circumflex artery. METHODS: Myoplasmic free Ca2+ (Ca(m)) was assessed with fura-2 in cells from sedentary (n=8) and aerobically exercise-trained (n=6) female Yucatan pigs after 6-month circumflex artery ameroid occlusion (OCC) and in cells from non-occluded, sedentary pigs (SED, n=5). First, Ca influx was induced by 80 mM KCl depolarization (priming step) followed by 5 mM caffeine to elicit maximal Ca2+ release and depletion. The SR was Ca-loaded again by depolarization and then exposed to caffeine after 2- or 11-min recovery to compare SR Ca2+ unloading. RESULTS: Baseline Ca(m), caffeine-induced peak Ca(m), and depolarization-induced maximum Ca(m) were decreased, and depolarization-induced time-to-half-maximum was increased in OCC vs. SED pigs, suggesting a tonic Ca2+ buffering (lowering) effect of occlusion. Exercise did not alter these effects. SR Ca2+ unloading occurred only in SED, as evidenced by decreased caffeine-induced Ca2+ release after 11 min of recovery, and was inhibited by low extracellular Na+. CONCLUSIONS: SR Ca2+ unloading can be demonstrated in coronary smooth muscle from sedentary pigs using a novel SR Ca2+ unloading protocol, and Ca2+ unloading partly depends on Na+-Ca2+ exchange activity. Furthermore, SR Ca2+ unloading in cells from non-occluded right coronary arteries of chronically circumflex-occluded pig hearts was not altered by exercise, perhaps due to enhanced tonic Ca2+ extrusion versus cells from normal, sedentary animals.

Adaptation, Physiological↗

PubMed2001

Separation and characterisation of five polar herbicides using countercurrent chromatography with detection by negative ion electrospray ionisation mass spectrometry.

Five polar herbicides were separated and characterised using high-speed analytical countercurrent chromatography (HSACCC) in conjunction with online electrospray mass spectrometry (ESI-MS). The countercurrent chromatography used a standard isocratic biphasic solvent system of hexane/ethyl acetate/methanol/water in reverse phase to effect the separation of these five environmentally important compounds. The chromatograph was coupled to a triple quadrupole mass spectrometer via a standard electrospray liquid chromatography interface that was able to give mass spectra in negative ion mode of each compound. Limits of detection are reported for this series of compounds along with representative negative ion ESI-MS data and calibrations for the separation.

Chromatography, High Pressure Liquid↗

PubMed2001

Endotoxin impairs agonist-stimulated intracellular free calcium (Ca(i)) responses in freshly dispersed aortic endothelial cells.

Impairment in endothelial cell intracellular free calcium (Ca(i)) mobilization mechanisms may contribute to decreased nitric oxide (NO) biosynthesis and impaired vasorelaxation responses of endotoxemic guinea pigs to endothelium-dependent vasodilators. We tested this hypothesis using fura-2 microfluorometry to compare agonist-stimulated Ca(i) responses of aortic endothelial cells freshly dispersed from guinea pigs 16 h after intraperitoneal injection of Escherichia coli endotoxin (lipopolysaccharide, LPS; 4 mg/kg) or saline (CON). In the presence of normal extracellular Ca2+ (2 mmol/L), basal (non-stimulated) endothelial Ca(i) (340/380 nm fluorescence ratio, R) was not different between CON and LPS cells (1.1 +/- 0.03 and 1.1 +/- 0.03, respectively). However, exposure to ADP (10 micromol/L) produced a biphasic increase in Ca(i) that was markedly decreased in cells from LPS-treated animals (P < 0.0001). Peak ADP-stimulated Ca(i) responses averaged 2.2 +/- 0.21 in CON cells and 1.5 +/- 0.11 (P < 0.01) in cells dispersed from LPS-treated animals. Exposure to acetylcholine (ACh; 10 micromol/L) produced sustained increases in Ca(i) (R = 1.4 +/- 0.13) in CON cells; however, LPS abolished Ca(i) responses to ACh. Exposure of endothelial cells to substance P (100 nmol/L) produced a biphasic increase in Ca(i) that was not different between groups. In the absence of extracellular Ca2+ (plus 10 micromol/L EGTA), exposure to ADP (10 micromol/L) produced transient increases in Ca(i) (Ca2+ release) that were decreased in cells from LPS-treated versus CON animals. Exposure to ACh in zero Ca2+ (10 micromol/L) produced smaller increases in Ca(i) (peak R = 1.3 +/- 0.12) in CON cells (when compared to ADP); however, Ca(i) responses to ACh remained absent in cells from LPS-treated animals. Re-exposure to Ca2+ produced sustained ACh-induced Ca(i) responses (Ca2+ influx) in cells from CON, but not LPS-treated animals; LPS markedly impaired (P< 0.05) ADP-induced sustained Ca(i) responses. Our data demonstrate that in vivo LPS exposure elicits decreased agonist-stimulated endothelial Ca(i) responses primarily involving impaired Ca2+ influx mechanisms. Known dependence of endothelial agonist-stimulated NO synthesis on Ca(i) suggests that defects in cell Ca2+ mobilization may contribute to LPS-induced impaired NO biosynthesis and decreased endothelium-dependent relaxation.

Animals↗

PubMed2000

Mature oligodendrocyte apoptosis precedes IGF-1 production and oligodendrocyte progenitor accumulation and differentiation during demyelination/remyelination.

We have documented changes in the oligodendrocyte population during demyelinating insult to the adult CNS. Feeding of cuprizone to adult mice led to apoptotic death of mature oligodendrocytes followed by profound demyelination of the corpus callosum. A regenerative response was initiated even during active demyelination. Oligodendrocyte progenitors have begun to proliferate and then accumulate within the lesion. Many of these cells may have migrated from the sub-ventricular zone and fornix before their accumulation in the demyelinating corpus callosum. The accumulation of differentiating oligodendrocyte progenitors was followed closely by the reappearance of mature oligodendrocytes and remyelination. Interestingly, an increase in IGF-1 mRNA was detected at Week 3 through Week 7, suggesting potential involvement in remyelination. Other factors, however, such as PDGF, NT3, FGF, jagged, and notch remained unchanged. These results suggest that the mature oligodendroglial population depleted by apoptosis is replaced by a newly formed oligodendroglial population derived from progenitors; these accumulate and seem to differentiate during remyelination.

Animals↗

PubMed2000

Purification and structural determination of SCB1, a gamma-butyrolactone that elicits antibiotic production in Streptomyces coelicolor A3(2).

Early stationary phase culture supernatants of Streptomyces coelicolor A3(2) contained at least four small diffusible signaling molecules that could elicit precocious antibiotic synthesis in the producing strain. The compounds were not detected in exponentially growing cultures. One of these compounds, SCB1, was purified to homogeneity and shown to be a gamma-butyrolactone of structure (2R, 3R,1'R)-2-(1'-hydroxy-6-methylheptyl)-3-hydroxymethylbutanolide . Bioassays of chemically synthesized SCB1, and of its purified stereoisomers, suggest that SCB1 acts in a highly specific manner to elicit the production of both actinorhodin and undecylprodigiosin, the two pigmented antibiotics made by S. coelicolor.

4-Butyrolactone↗

PubMed2000

The structure of ribonuclease P protein from Staphylococcus aureus reveals a unique binding site for single-stranded RNA.

Ribonuclease P (RNaseP) catalyses the removal of the 5'-leader sequence from pre-tRNA to produce the mature 5' terminus. The prokaryotic RNaseP holoenzyme consists of a catalytic RNA component and a protein subunit (RNaseP protein), which plays an auxiliary but essential role in vivo by binding to the 5'-leader sequence and broadening the substrate specificity of the ribozyme. We determined the three-dimensional high-resolution structure of the RNaseP protein from Staphylococcus aureus (117 amino acid residues) by nuclear magnetic resonance (NMR) spectroscopy in solution. The protein has an alphabeta-fold, similar to the ribonucleoprotein domain. We used small nucleic acid molecules as a model for the 5'-leader sequence to probe the propensity for generic single-stranded RNA binding on the protein surface. The NMR results reveal a contiguous interaction site, which is identical with the previously identified leader sequence binding site in RNaseP holoenzyme. The conserved arginine-rich motif does not bind single-stranded RNA. It is likely that this peptide segment binds selectively to double-stranded sections of P RNA, which are conformationally more rigid. Given the essentiality of RNaseP for the viability of the organism, knowledge of the S. aureus protein structure and insight into its interaction with RNA will help us to develop RNaseP and RNaseP protein as targets for novel antibiotics against this pathogen.

Amino Acid Sequence↗

PubMed2000

Intra and inter technologist variability in the quality assessment of respiratory tract specimens.

The majority of microbiology laboratories have implemented quality improvement procedures such as a Q scoring system to assess the nature of clinical specimens. Our study reviewed the sources and the amount of variation when Q scoring of lower respiratory secretions was performed. In total, 450 slides representing lower respiratory tract secretions were Q scored by three experienced technologists. Total agreement regarding the number of neutrophils, squamous epithelial cells and Q scores was 76%, 57% and 57% respectively. The major factor influencing Q score values was the enumeration of epithelial cells. From our findings, we expect that there is greater variability in Q scoring then is generally acknowledged and there is a substantial degree of subjectivity on part of individual technologists reading gram stains.

Diagnostic Techniques, Respiratory System↗

PubMed2000

A potent seryl tRNA synthetase inhibitor SB-217452 isolated from a Streptomyces species.

A potent inhibitor of seryl tRNA synthetase, designated SB-217452 has been isolated from Streptomyces sp. ATCC 700974. The fermentation, isolation, structure elucidation and some properties are described. SB-217452 showed inhibitory activity against both Staphylococcus aureus and rat seryl tRNA synthetases, with similar IC50 values of approximately 8 nM. The inhibitor is the serine linked nucleoside moiety of the antibiotic albomycin delta2. In contrast to albomycin delta2, SB-217452 showed only very weak antibacterial activity against a limited range of microorganisms. The compound has not been previously reported as a naturally occurring metabolite. In addition to SB-217452, albomycin delta2 Fe3+ complex and the novel Al3+ complex were isolated from the fermentation. These complexes had no seryl tRNA synthetase inhibitory activity.

Animals↗

PubMed1999

Pairwise interactions between neuronal alpha7 acetylcholine receptors and alpha-conotoxin ImI.

The present work uses alpha-conotoxin ImI (CTx ImI) to probe the neurotransmitter binding site of neuronal alpha7 acetylcholine receptors. We identify key residues in alpha7 that contribute to CTx ImI affinity, and use mutant cycles analysis to identify pairs of residues that stabilize the receptor-conotoxin complex. We first mutated key residues in the seven known loops of alpha7 that converge at the subunit interface to form the ligand binding site. The mutant subunits were expressed in 293 HEK cells, and CTx ImI binding was measured by competition against the initial rate of 125I-alpha-bungarotoxin binding. The results reveal a predominant contribution by Tyr-195 in alpha7, accompanied by smaller contributions by Thr-77, Tyr-93, Asn-111, Gln-117, and Trp-149. Based upon our previous identification of bioactive residues in CTx ImI, we measured binding of receptor and toxin mutations and analyzed the results using thermodynamic mutant cycles. The results reveal a single dominant interaction between Arg-7 of CTx ImI and Tyr-195 of alpha7 that anchors the toxin to the binding site. We also find multiple weak interactions between Asp-5 of CTx ImI and Trp-149, Tyr-151, and Gly-153 of alpha7, and between Trp-10 of CTx ImI and Thr-77 and Asn-111 of alpha7. The overall results establish the orientation of CTx ImI as it bridges the subunit interface and demonstrate close approach of residues on opposing faces of the alpha7 binding site.

Amino Acid Sequence↗

PubMed1999

Redox manipulation using the thiol-oxidizing agent diethyl maleate prevents hepatocellular necrosis and apoptosis in a rodent endotoxemia model.

Manipulation of the intracellular redox state has been shown to alter cell activation pathways with resultant changes in cellular function. Previous studies have suggested that thiol oxidation, using the glutathione-depleting agent diethyl maleate (DEM), was able to inhibit endothelial cell activation. We hypothesized that this agent might exert beneficial effects following endotoxemia in the rat, a model in which transendothelial migration of neutrophils is central to the development of hepatocellular injury. Sprague-Dawley rats treated intraperitoneally with lipopolysaccharide (LPS) (200 microg/kg) plus D-galactosamine (GalN) (600 mg/kg) developed hepatocellular necrosis, as evidenced by liver enzyme release and morphological changes. Pretreatment with DEM abrogated this injury in a dose-dependent fashion. Histology revealed reduced neutrophil accumulation in both the parenchyma and sinusoids, consistent with reduced neutrophil sequestration and transendothelial migration. This effect appeared to be related to the ability of DEM to prevent LPS-induced up-regulation of both vascular cell adhesion molecule-1 (VCAM-1) mRNA and intercellular adhesion molecule-1 (ICAM-1) mRNA in the liver, as well as reducing tumor necrosis factor (TNF) mRNA expression. In addition, DEM prevented hepatocyte apoptosis following LPS treatment. The effect was reproduced when TNF was used as an inflammatory stimulus, suggesting a direct protective effect on the hepatocyte. Taken together, these studies show that redox manipulation through thiol oxidation may represent a novel approach to preventing liver necrosis and apoptosis in inflammatory conditions.

Alanine Transaminase↗

PubMed1999

A comparison of the effects of three chelating agents on the root canals of extracted human teeth.

The effects of EDTA were compared in vitro with the effects of two other chelating agents: succimer and trientine HCl. Thirty extracted human teeth with single canals were used. Groups of 10 were treated by the three agents and then examined under the scanning electron microscope. The results showed that EDTA widened the dentinal tubules. Trientine HCl also produced widening of the dentinal tubules very similar to EDTA, whereas succimer produced more extensive widening.

Chelating Agents↗

PubMed1999

Daily times four vinorelbine plus cisplatin in advanced non-small-cell lung cancer: a phase II trial of a novel schedule.

PURPOSE: To evaluate the efficacy of a novel multiday schedule of vinorelbine and displatin in patients with advanced NSCLC. PATIENTS AND METHODS: Thirty patients were enrolled, including 27 patients with stage IV disease, and 11 patients with performance status of 2. They received a maximum of four chemotherapy cycles with cisplatin 20 mg/m2/day and vinorelbine 15 mg/m2/day intravenously (i.v.) for four consecutive days, every three weeks, with prophylactic filgrastim. RESULTS: Sixteen patients responded (53%, 95% confidence interval (95% CI): 34%-72%), including two complete and fourteen partial confirmed responses. Median survival for all patients was 8.1 months, with actuarial one-year and two-year survival rates of 40% and 15%. Despite prophylactic filgrastim, the delivered vinorelbine dose intensity of 16.8 mg/m2/week caused febrile neutropenia in 48% of patients (16% of cycles), resulting in one treatment-related death. Common nonhematologic toxicities included delayed emesis, asthenia, and constipation. CONCLUSIONS: This multiday vinorelbine-cisplatin schedule is highly active against advanced NSCLC but results in frequent neutropenic complications. The myelotoxicity and antitumor efficacy of vinorelbine in NSCLC patients may be schedule-dependent.

Adult↗

PubMed1999

Contractile function and myoplasmic free Ca2+ (Cam) in coronary and mesenteric arteries of endotoxemic guinea pigs.

Endotoxin-induced vascular hyporesponsiveness could potentially involve alterations of vascular smooth muscle (VSM) myoplasmic free calcium (Ca(m)) mobilization mechanisms. Contractile function and Ca(m)(fura-2 microfluorometry) regulation were evaluated in vitro using coronary (COR) and mesenteric (MES) artery preparations (100-250 microm inner diameter) isolated from guinea pigs 16 h after intraperitoneal (i.p.) injection of either saline (control; CON) or Escherichia coli endotoxin lipopolysaccharide (LPS; 4 mg/kg). Concentration-response relationships to K+ (5-100 mM) were significantly enhanced in both COR and MES arteries isolated from LPS-treated animals. In contrast, contractile responses to prostaglandin F2alpha (PGF2alpha; 1-100 microM) were markedly impaired in COR and MES arteries from LPS-treated animals, while endothelin-1 (ET; 1-100 nM)-mediated contractile responses of these arteries were enhanced at the maximal dose (100 nM). In COR arteries, PGF2alpha (1-100 microM) and ET (1-100 nM) produced biphasic increases in Ca(m) in both CON and LPS groups. No significant differences were observed in either the initial transient peak or secondary sustained Ca(m) responses between groups, suggesting a lack of effect of LPS upon intracellular Ca2+ release or Ca2+ influx mechanisms in COR arteries. Exposure of MES arteries to PGF2alpha and ET produced concentration-dependent increases in Ca(m) in both groups. However, Ca(m) responses of MES arteries lacked initial peak responses, suggesting potential differences in Ca(m) mobilization between COR and MES arteries. Ca(m) responses to K+ (80 mM) and PGF2alpha (1-100 microM) were similar in MES arteries from both groups; however, ET-mediated increases in Ca(m) were significantly blunted in LPS compared with CON MES arteries. Thus, endotoxemia produced differential effects upon depolarization (K4) and receptor (PGF2alpha, ET)-mediated contractile responses in both COR and MES arteries. Reductions in VSM Ca(m) mobilization appear unlikely as a mechanism for LPS-induced impairment of contractile function of COR and MES arteries; other mechanisms (i.e., decreased Ca2+ sensitivity of contractile proteins) may be involved in effects of LPS upon VSM function of COR and MES arteries.

Animals↗

PubMed1999

Function search in a large transcription factor gene family in Arabidopsis: assessing the potential of reverse genetics to identify insertional mutations in R2R3 MYB genes.

More than 92 genes encoding MYB transcription factors of the R2R3 class have been described in Arabidopsis. The functions of a few members of this large gene family have been described, indicating important roles for R2R3 MYB transcription factors in the regulation of secondary metabolism, cell shape, and disease resistance, and in responses to growth regulators and stresses. For the majority of the genes in this family, however, little functional information is available. As the first step to characterizing these genes functionally, the sequences of >90 family members, and the map positions and expression profiles of >60 members, have been determined previously. An important second step in the functional analysis of the MYB family, through a process of reverse genetics that entails the isolation of insertion mutants, is described here. For this purpose, a variety of gene disruption resources has been used, including T-DNA-insertion populations and three distinct populations that harbor transposon insertions. We report the isolation of 47 insertions into 36 distinct MYB genes by screening a total of 73 genes. These defined insertion lines will provide the foundation for subsequent detailed functional analyses for the assignment of specific functions to individual members of the R2R3 MYB gene family.

Arabidopsis↗

PubMed1999

Delayed treatment with diethyl maleate prevents E-selectin expression in human endothelial cells.

BACKGROUND: Polymorphonuclear leukocyte (PMN) infiltration is a significant contributor to tissue damage in many disease states and is known to occur through an orderly set of events. The endothelial cell adhesion molecule E-selectin is involved in the initial rolling of PMNs on the endothelium at sites of inflammation. We have previously shown that the glutathione depleting agent diethyl maleate (DEM) attenuates lung injury in a rodent model of intratracheal LPS stimulation. We hypothesized that DEM might attenuate E-selectin in LPS-treated human umbilical vein endothelial cells as a mechanism underlying this effect. Further, we investigated the role of delayed treatment with DEM on E-selectin expression. METHODS: Human umbilical vein endothelial cells were treated with DEM (100 to 400 mumol/L) before or after LPS stimulation (1 microgram/mL). Surface expression of E-selectin was examined using a cellular enzyme-linked immunosorbent assay. E-selectin mRNA transcripts were detected by Northern blot analysis. Nuclear factor-kappa B (NF-kappa B) activity was detected with gel shift assays. RESULTS: DEM significantly inhibited LPS-induced E-selectin surface expression and mRNA levels in a dose-dependent fashion, with complete inhibition at 250 mumol/L, without affecting cell viability. This inhibitory effect was seen even if DEM was added up to 60 minutes after LPS. DEM inhibited NF-kappa B nuclear translocation in a manner that mirrored protein and mRNA levels. CONCLUSIONS: Delayed treatment with DEM attenuates NF-kappa B nuclear translocation and E-selectin expression in human umbilical vein endothelial cells up to 60 minutes after the onset of LPS stimulation. Thus, DEM may represent an effective intervention for PMN-mediated organ injury even when given after an inflammatory insult.

Cells, Cultured↗

PubMed1998

The glutathione depleting agent diethylmaleate prolongs renal allograft survival.

INTRODUCTION: Intercellular adhesion molecule 1 (ICAM-1) plays an important role in mediating allograft rejection through its role in cellular trafficking and as an important costimulatory signal mediating T cell activation. We have previously reported that systemic administration of the glutathione (GSH) depleting agent diethylmaleate (DEM) prevents upregulation of ICAM-1 in various inflammatory models, suggesting that this agent may offer benefit in preventing allograft rejection. Thus we evaluated the effects of DEM in a murine model of renal transplantation. METHODS: Kidneys from C57BL/6 mice were transplanted into MHC incompatible C3H mice. Donors were treated with DEM 1 h prior to sacrifice, whereas recipients received DEM 1 h following transplantation. Animals were followed until the time of death. In separate studies, renal ICAM-1 mRNA expression was evaluated by polymerase chain reaction and the CD4(+) T cell cytokine profile evaluated in a mixed lymphocyte reaction using C3H responder splenocytes and C57BL/6 stimulator cells. RESULTS: Pretreatment with DEM increased survival from 18.9 +/- 3.6 to 30.6 +/- 10 days (P < 0.05). This increase in survival was associated with a reduction in renal ICAM-1 mRNA expression. Mixed lymphocyte cultures derived from animals pretreated with DEM demonstrated a reduction in the Th1 cytokines IFN-gamma and IL-2 and an increase in the Th2 cytokines IL-4 and IL-10. CONCLUSION: Administration of DEM with consequent systemic GSH depletion significantly reduces allograft ICAM-1 expression and prolongs graft survival. Although speculative, a shift from a Th1 to a Th2 cytokine response raises the possibility that tolerance induction plays a role in prolonged allograft survival.

Animals↗

PubMed1997

Glutathione depletion prevents lipopolysaccharide-induced local skin inflammation.

BACKGROUND: We have previously shown that the thiol-oxidizing agent diethyl maleate prevents lipopolysaccharide (LPS)-induced up-regulation of endothelial cell intercellular adhesion molecule-1 (ICAM-1) in vitro. OBJECTIVE: To determine the effect of glutathione depletion on the development of local skin inflammation in vivo, a model known to be dependent on ICAM-1. DESIGN: Swiss Webster mice were injected with intradermal LPS (30 micrograms) or isotonic saline solution. INTERVENTION: Mice were pretreated for 1 hour with intraperitoneal diethyl maleate (6 mmol/kg) or corn oil vehicle. MAIN OUTCOME MEASURES: Injection sites were harvested after 12 and 24 hours and evaluated for changes in vascular permeability and histological characteristics. To determine the mechanism underlying our findings, we evaluated skin ICAM-1 immunohistochemistry, levels of ICAM-1 protein and messenger RNA (mRNA), and neutrophil CD11b expression at the 24-hour point. RESULTS: Diethyl maleate significantly decreased the skin permeability index in a dose-dependent fashion at 24 hours but not at 12 hours. Skin histological examination under light microscopy showed a marked LPS-induced neutrophil infiltration at 24 hours, which was inhibited with diethyl maleate pretreatment. Immunohistochemical examination showed that diethyl maleate reduced ICAM-1 expression. In keeping with the hypothesized mechanism, diethyl maleate attenuated the LPS-induced up-regulation of ICAM-1 mRNA by 44%. Diethyl maleate also slightly but insignificantly reduced CD11b expression in vivo. CONCLUSIONS: Diethyl maleate markedly attenuates LPS-induced dermal inflammation, primarily through a reduction in ICAM-1 protein and mRNA expression. These data suggest that manipulation of the intracellular redox state may have a beneficial role in neutrophil-mediated inflammation.

Animals↗