Biomedical subjects

S J Lee

Publications and source records attributed to S J Lee.

At least 19 recordsLinked to original sources

PubMed2001

First observation of the sigma(+)(c) baryon and a new measurement of the sigma(+)(c) mass.

Using data recorded with the CLEO II and CLEO II.V detector configurations at the Cornell Electron Storage Rings, we report the first observation and mass measurement of the Sigma(*+)(c) charmed baryon, and an updated measurement of the mass of the Sigma(+)(c) baryon. We find M(Sigma(*+)(c))-M(Lambda(+)(c)) = (231.0+/-1.1+/-2.0) MeV, and M(Sigma(+)(c))-M(Lambda(+)(c)) = (166.4+/-0.2+/-0.3) MeV, where the errors are statistical and systematic, respectively.

Journal Article↗

PubMed2001

Augmented death in immunostimulated astrocytes deprived of glucose: inhibition by an iron porphyrin FeTMPyP.

The present study shows that under glucose-deprived conditions immunostimulated astrocytes rapidly undergo death due to their increased susceptibility to endogenously produced peroxynitrite. Fe(III)tetrakis(N-methyl-4'-pyridyl)porphyrin (FeTMPyP), but not the structurally related compounds ZnTMPyP and H(2)TMPyP, prevented the death in glucose-deprived immunostimulated astrocytes. Consistently, FeTMPyP, not ZnTMPyP and H(2)TMPyP, completely blocked the elevation of nitrotyrosine immunoreactivity (a marker of peroxynitrite) and the depolarization of the mitochondrial transmembrane potential in glucose-deprived immunostimulated astrocytes. The present data suggest that peroxynitrite may be associated with glial cell death during metabolic deterioration in the cerebral ischemic penumbra.

Animals↗

PubMed2001

Recovery after stem-cell transplantation for hematologic diseases.

PURPOSE: Although the number of autologous and allogeneic stem-cell transplantations (SCT) is increasing, relatively little information about recovery after transplantation is available. Quantitative information appropriate for patient counseling is difficult to discern from the literature. We sought to suggest reasonable expectations for recovery and symptoms after SCT for hematologic malignancies and other disorders using the following measures: (1) objective measures of health status, such as frequency of clinic visits, need for rehospitalization, medication usage, work status, and overall and event-free survival; (2) qualitative assessment of quality of life, such as returning to a normal life, resumption of normal activities, satisfaction with appearance, and whether recovery has occurred; and (3) quantification of specific bothersome symptoms. PATIENTS AND METHODS: Autologous and allogeneic SCT recipients at a tertiary-care transplant center participated in the prospective, longitudinal questionnaire study. RESULTS: Three hundred twenty patients were studied. Questionnaire response rates at 6, 12, and 24 months range from 85% to 88% among survivors. Although autologous patients had better event-free and overall survival, fewer symptoms, and more complete recovery at 6 months, these advantages had largely equalized by 12 months. Specific bothersome symptoms were reported by less than 24% of patients after transplantation, except for fatigue and financial and sexual difficulties, which were more prevalent. CONCLUSION: These findings may help counsel patients considering transplantation and educate them about reasonable expectations for recovery. Overall, the low level of bothersome symptoms and continued recovery through the first year after transplantation are encouraging.

Activities of Daily Living↗

PubMed2001

The p38 mitogen-activated protein kinase pathway regulates interleukin-6 synthesis in response to tumor necrosis factor in osteoblasts.

The induction of interleukin-6 (IL-6), using a proinflammatory cytokine (tumor necrosis factor-alpha), was studied in a human osteoblast cell line (MG-63) in relation to p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappaB transcription factor. When added to MG-63 cells, tumor necrosis factor-alpha (TNF-alpha) had a stimulatory effect on the production of IL-6, and this elevation was significantly reduced by SB203580, a specific p38 MAPK inhibitor. In addition, the stimulation of IL-6 release was also reduced by pyrrolidine dithiocarbamate (PDTC) or NF-kappaB SN50, which has been reported to be a potent NF-kappaB inhibitor. Both the NF-kappaB inhibitors in the presence of SB203580 had a more inhibitory effect on IL-6 release. In this study, TNF-alpha stimulated NF-kappaB binding affinity as well as p38 MAP kinase activation, leading to the release of IL-6. However, the specific inhibitor of p38 MAPK, SB203580, had no effect on TNF-alpha-induced NF-kappaB activation and both NF-kappaB inhibitors failed to reduce the p38 MAPK activation in the TNF-alpha-stimulated osteoblasts. In addition, inhibition of p38 MAPK partially, but significantly, impaired TNF-alpha-regulated release of osteocalcin, an important differentiation marker in osteoblasts. These results strongly suggest that both p38 MAPK and NF-kappaB are required in TNF-alpha-induced IL-6 synthesis and that these two TNF-alpha-activated pathways can be primarily dissociated. Furthermore, p38 MAPK may play a significant role in differentiation in MG-63 cells.

Antioxidants↗

PubMed2001

Optimization of fermentation conditions for the production of bacterial cellulose by a newly isolated Acetobacter sp. A9 in shaking cultures.

The optimum fermentation conditions for the production of cellulose by a newly isolated Acetobacter sp. A9 were determined by shaken cultures. The strain was able to produce cellulose at 25-30 degrees C with a maximum at 30 degrees C. Cellulose production occurred at pH 4.5-7.5 with a maximum at pH 6.5. The improved medium composition was 4% (w/v) glucose, 0.1% (w/v) yeast extract, 0.7% (w/v) polypeptone and 0.8% (w/v) Na(2)HPO(4).12H(2)O. Under these culture conditions, 3.8 g/l cellulose was produced after 7 days of cultivation, although this strain produced only 2.2 g/l in the standard medium. The addition of ethanol to the improved medium enhanced cellulose production: in an improved medium containing 1.4% (v/v) ethanol, cellulose production was 15.2 g/l, which was about four times higher than that without ethanol. Addition of ethanol was found to eliminate the spontaneous mutation of Acetobacter sp. A9.

Acetobacter↗

PubMed2001

Prophylactic efficacy of a new gentamicin-releasing urethral catheter in short-term catheterized rabbits.

OBJECTIVE: To describe an indwelling urethral catheter coated with gentamicin sulphate on the inner and outer surface of the catheter, and to evaluate the efficacy and safety of this catheter in preventing catheter-associated infections in rabbits. Materials and methods Sixty rabbits were divided equally into control and experimental groups which were then subdivided equally according to the duration of catheterization (1, 3 and 5 days). Silicone-treated latex catheters were used in the control group and gentamicin-releasing catheters in the experimental group. Urine samples and surface swabs from the catheter were cultured for bacteriological assessment, and the catheter surface examined by scanning electron microscopy to structurally analyse the biofilms. RESULTS: The gentamicin-releasing catheter reduced the incidence of bacteriuria (defined as > or = 100 c.f.u./mL) after both 3 and 5 days of catheterization (eight and 10 rabbits, respectively, for the control catheter, vs two and four rabbits for the gentamicin-releasing catheter, P < 0.05). The surfaces of the gentamicin-releasing catheter were colonized less often than those of the control catheter after both 3 and 5 days (eight and 10, respectively, for the control, vs one and four for the gentamicin-releasing catheter, P < 0.05). Scanning electron microscopy showed the formation of bacterial biofilm throughout the 3-day and 5-day control catheters, but deterioration of the bacterial biofilm was visible on the surface of the gentamicin-releasing catheters. CONCLUSION: This new gentamicin-releasing catheter produced an antibacterial barrier which inhibited catheter-associated urinary tract infection with no toxicity for at least 5 days. These in vivo studies suggest that this new catheter may be useful for controlling infection, with systemic and local safety, in patients undergoing short-term indwelling urethral catheterization.

Animals↗

PubMed2001

Experimental salivary pellicles on the surface of orthodontic materials.

The purpose of this study was to define the composition of salivary pellicles that form on the surfaces of orthodontic materials and to further investigate whether qualitative differences exist between the composition of adsorbed salivary pellicles that form on 3 different orthodontic materials: stainless steel bracket metal, elastomeric ligature ring, and bracket bonding resin. Experimental pellicles were formed by incubating these materials in fresh human parotid or submandibular-sublingual saliva for 2 hours. Pellicles were extracted with sodium dodecyl sulfate buffer and lyophilized. They were then subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting to identify the adsorbed salivary components. Remarkable differences in the profiles of pellicle components were found, dependent on the type of orthodontic materials. The pellicle components on the bracket metal were almost the same as those found on the elastomeric ligature ring. Salivary protein adsorption patterns to bonding resin showed different features. Distinct differences were also found between the surface-binding affinities of the same salivary proteins from different glandular salivas. These results may be explained on the basis that binding sites for specific proteins on the surfaces of the materials are covered by molecules of submandibular-sublingual saliva, probably mucins. The results of this study provide valuable information concerning initial bacterial adhesion to the surfaces of orthodontic materials, as well as information that could be used in the development of orthodontic materials with enhanced surface properties.

Adhesives↗

PubMed2001

Novel target sites for estrogen action in the dorsal hippocampus: an examination of synaptic proteins.

Structural studies have shown that estrogens increase dendritic spine number in the dorsal CA1 field of rat hippocampus using Golgi impregnation as well as the number of dorsal CA1 synapses visualized via electron microscopy. The present study was carried out to further these findings by examining changes in the levels of pre- and postsynaptic proteins using radioimmunocytochemistry (RICC). In this study, 2 days of estradiol-benzoate treatment produced significant and comparable increases in synaptophysin, syntaxin, and spinophilin immunoreactivity (IR) in the CA1 region of the dorsal hippocampus of ovariectomized female rats. For spinophilin, IR was also increased in the hilar region of the dentate gyrus as well as CA3. In all cases, the nonsteroidal estrogen antagonist CI628, which has been previously shown to block spine formation, inhibited the effects of estrogen. However, these protein differences were not detected in whole hippocampus using Western blots. These findings add to a growing body of evidence that estrogens increase synapses in the CA1 region of hippocampus along with changes in previously unidentified sites. These results also suggest that RICC is a rapid and sensitive method for examining molecular changes in synaptic profiles in anatomically distinct brain regions.

Animals↗

PubMed2000

Protein kinase C-related kinase 2 phosphorylates the protein synthesis initiation factor eIF4E in starfish oocytes.

Phosphorylation of eIF4E is required for protein synthesis during starfish oocyte maturation. The activity of protein kinase C-related kinase 2 (PRK2) increases prior to the phosphorylation of eIF4E (G. Stapleton et al., 1998, Dev. Biol. 193, 34-46). We investigate here whether eIF4E is activated by PRK2. A 3.5-kb eIF4E clone isolated from starfish cDNA is 57% identical to human eIF4E and contains the putative phosphorylation site serine-209. The serine-209 environment (SKTGS(209)MAKSRF) is similar to the consensus sequence of the phosphorylation site of protein kinase C and related kinases. A starfish eIF4E fusion protein (GST-4E) was phosphorylated in vitro by PRK2 in the presence of 1,2-diolyl-sn-glycerol 3-phosphate. In contrast, replacing the GST-4E serine-209 with an alanine significantly reduced this phosphorylation. Analysis by two-dimensional phosphopeptide mapping reveals a major phosphopeptide in trypsin-digested GST-4E, but not in its serine-209 mutant. Importantly, this major phosphopeptide in GST-4E corresponds to a major phosphopeptide of eIF4E isolated from (32)P-labeled oocytes. Thus, PRK2 may regulate translation initiation during oocyte maturation by phosphorylating the serine-209 residue of eIF4E in starfish. We also demonstrate that high levels of cAMP inhibit the activation of PRK2, eIF4E, and the eIF4E binding protein during starfish oocyte maturation, while PI3 kinase activates these proteins.

Alanine↗

PubMed2000

Entropic stabilization of the tryptophan synthase alpha-subunit from a hyperthermophile, Pyrococcus furiosus. X-ray analysis and calorimetry.

The structure of the tryptophan synthase alpha-subunit from Pyrococcus furiosus was determined by x-ray analysis at 2.0-A resolution, and its stability was examined by differential scanning calorimetry. Although the structure of the tryptophan synthase alpha(2)beta(2) complex from Salmonella typhimurium has been already determined, this is the first report of the structure of the alpha-subunit alone. The alpha-subunit from P. furiosus (Pf-alpha-subunit) lacked 12 and 6 residues at the N and C termini, respectively, and one residue each in two loop regions as compared with that from S. typhimurium (St-alpha-subunit), resulting in the absence of an N-terminal helix and the shortening of a C-terminal helix. The structure of the Pf-alpha-subunit was essentially similar to that of the St-alpha-subunit in the alpha(2)beta(2) complex. The differences between both structures were discussed in connection with the higher stability of the Pf-alpha-subunit and the complex formation of the alpha- and beta-subunits. Calorimetric results indicated that the Pf-alpha-subunit has extremely high thermostability and that its higher stability is caused by an entropic effect. On the basis of structural information of both proteins, we analyzed the contributions of each stabilization factor and could conclude that hydrophobic interactions in the protein interior do not contribute to the higher stability of the Pf-alpha-subunit. Rather, the increase in ion pairs, decrease in cavity volume, and entropic effects due to shortening of the polypeptide chain play important roles in extremely high stability in Pf-alpha-subunit.

Amino Acid Sequence↗

PubMed2000

Effects of brain-derived neurotrophic factor and neurotrophin-3 on expression of mRNAs encoding c-Fos, neuropeptides and glutamic acid decarboxylase in cultured spinal neurons.

There is growing evidence suggesting that neurotrophins have modulating effects on the pain signaling system at spinal levels. In order to determine whether neurotransmitter expression is modulated in response to the elevation of neurotrophins, the changes in c-fos, neuropeptide and glutamic acid decarboxylase (GAD) mRNAs expression was evaluated after BDNF or NT-3 was applied to cultured spinal neurons. Reverse transcription polymerase chain reaction analysis revealed that BDNF induced a significant increase in the expression of preprodynorphin (pDYN), preproenkephalin (pENK), neuropeptide Y (NPY) and GAD mRNAs. In contrast, the pENK, not the pDYN, NPY and GAD, mRNA levels increased after the treatment of NT-3. Both BDNF and NT-3 produced a rapid increase in c-fos mRNA. These results suggest that BDNF and NT-3 have differential neuronal effects on the synthesis of spinal cord neurotransmitters that are involved in the modulation of nociceptive information.

Animals↗

PubMed2000

A nucleolar protein related to ribosomal protein L7 is required for an early step in large ribosomal subunit biogenesis.

The Saccharomyces cerevisiae Rlp7 protein has extensive identity and similarity to the large ribosomal subunit L7 proteins and shares an RNA-binding domain with them. Rlp7p is not a ribosomal protein; however, it is encoded by an essential gene and therefore must perform a function essential for cell growth. In this report, we show that Rlp7p is a nucleolar protein that plays a critical role in processing of precursors to the large ribosomal subunit RNAs. Pulse-chase labeling experiments with Rlp7p-depleted cells reveal that neither 5.8S(S), 5.8S(L), nor 25S is produced, indicating that both the major and minor processing pathways are affected. Analysis of processing intermediates by primer extension indicates that Rlp7p-depleted cells accumulate the 27SA(3) precursor RNA, which is normally the major substrate (85%) used to produce the 5.8S and 25S rRNAs, and the ratio of 27SB(L) to 27SB(S) precursors changes from approximately 1:8 to 8:1 (depleted cells). Because 27SA(3) is the direct precursor to 27SB(S), we conclude that Rlp7p is specifically required for the 5' to 3' exonucleolytic trimming of the 27SA(3) into the 27SB(S) precursor. As it is essential for processing in both the major and minor pathways, we propose that Rlp7p may act as a specificity factor that binds precursor rRNAs and tethers the enzymes that carry out the early 5' to 3' exonucleolytic reactions that generate the mature rRNAs. Rlp7p may also be required for the endonucleolytic cleavage in internal transcribed spacer 2 that separates the 5.8S rRNA from the 25S rRNA.

Cell Nucleolus↗

PubMed2000

Mutations at lysine 525 of inducible nitric-oxide synthase affect its Ca2+-independent activity.

Calmodulin binding to inducible nitric-oxide synthase may play an important role in its Ca(2+)-independent activity. Studies of inducible nitric-oxide synthase chimeras containing the calmodulin binding sequence of neuronal or endothelial nitric-oxide synthases show that the calmodulin binding sequence of inducible nitric-oxide synthase is necessary but not sufficient for the Ca(2+)-independent activity. The mutations at lysine 525 located at the C terminus of the calmodulin binding sequence of inducible nitric-oxide synthase were examined for the effects on the Ca(2+)-independent activity with chimeras containing the oxygenase or reductase domains of inducible or neuronal nitric-oxide synthases. Results show that the Ca(2+)-independent binding of calmodulin is not solely responsible for maximal Ca(2+)-independent activity of inducible nitric-oxide synthase. Lysine 525 of inducible nitric-oxide synthase may also play an important role in coordinating the maximal Ca(2+)-independent activity.

Amino Acid Sequence↗

PubMed2000

Effects of tumor necrosis factor-alpha and interferon-gamma on expressions of matrix metalloproteinase-2 and -9 in human bladder cancer cells.

We have investigated the effects of tumor necrosis factor-alpha (TNF-alpha) and interferon (INF-gamma), the potent Bacillus Calmette-Guerin (BCG)-induced cytokines on the production of MMP-2, MMP-9, TIMP-1, TIMP-2 and MT1-MMP in high grade human bladder cancer cell lines, T-24, J-82 and HT-1376 cell lines. MMP-2 expression and activity were decreased in T-24 cells treated with both cytokines in a dose dependent manner. However, J-82 cells treated with TNF-alpha and INF-gamma revealed dose dependent increases of MMP-9 expression and activity with similar baseline expression and activity of MMP-2. HT-1376 cells after exposure to TNF-alpha only enhanced the expression and activity of MMP-9. These results indicate that TNF-alpha and INF-gamma could regulate the production of MMP-2 or MMP-9 on bladder cancer cells and their patterns of regulation are cell specific. Furthermore, this diverse response of bladder cancer cells to TNF-alpha and INF-gamma suggests that BCG immunotherapy may enhance the invasiveness of bladder cancer in certain conditions with induction of MMPs.

Dose-Response Relationship, Drug↗

PubMed2000

Patient preferences for axillary dissection in the management of early-stage breast cancer.

BACKGROUND: Recent data on the value of adjuvant therapy in lymph node-negative breast cancer and promising early data on less invasive strategies for managing the axilla have raised questions about the appropriate role of axillary lymph node dissection (ALND) in the management of early-stage breast cancer. We sought to evaluate how women weigh potential benefits of ALND-prognostic information, enhanced local control, and tailored therapy-against the risks of long-term morbidity that are associated with the procedure. METHODS: We used hypothetical scenarios to survey 82 randomly selected women with invasive breast cancer who had been treated with ALND and 62 women at risk for invasive breast cancer by virtue of a history of ductal carcinoma in situ (DCIS) who had not undergone ALND. RESULTS: Women in both the invasive cancer and the DCIS groups required substantial improvements in local control of the cancer (5% and 15%, respectively) and overall survival (3% and 10%, respectively) before they would opt for this procedure. Women with invasive cancer would choose ALND if it had only a 1% chance of altering treatment recommendations, whereas DCIS subjects required a 25% chance. Sixty-eight percent and 29% of women in the invasive cancer and DCIS groups, respectively, would accepted a 40% risk of arm dysfunction to gain prognostic information that would not change treatment. CONCLUSIONS: For most subjects treated previously for invasive breast cancer and almost half those at risk of the disease, the potential benefits of ALND, particularly the value of prognostic information, were sufficient to outweigh the risks of morbidity. However, women varied considerably in their preferences, highlighting the need to tailor decisions regarding management of the axilla to individual patients' values.

Adult↗

PubMed2000

Signal transduction between a membrane-bound transporter, PtsG, and a soluble transcription factor, Mlc, of Escherichia coli.

The global regulator Mlc controls several genes implicated in sugar utilization systems, notably the phosphotransferase system (PTS) genes, ptsG, manXYZ and ptsHI, as well as the malT activator. No specific low molecular weight inducer has been identified that can inactivate Mlc, but its activity appeared to be modulated by transport of glucose via Enzyme IICB(Glc) (PtsG). Here we demonstrate that inactivation of Mlc is achieved by sequestration of Mlc to membranes containing dephosphorylated Enzyme IICB(Glc). We show that Mlc binds specifically to membrane fractions which carry PtsG and that excess Mlc can inhibit Enzyme IICB(Glc) phosphorylation by the general PTS proteins and also Enzyme IICB(Glc)-mediated phosphorylation of alpha-methylglucoside. Binding of Mlc to Enzyme IICB(Glc) in vitro required the IIB domain and the IIC-B junction region. Moreover, we show that these same regions are sufficient for Mlc regulation in vivo, via cross-dephosphorylation of IIB(Glc) during transport of other PTS sugars. The control of Mlc activity by sequestration to a transport protein represents a novel form of signal transduction in gene regulation.

Bacterial Proteins↗

PubMed2000

Effects of 17beta-estradiol and testosterone on hepatic mRNA/protein levels and catalytic activities of CYP2M1, CYP2K1, and CYP3A27 in rainbow trout (Oncorhynchus mykiss).

There is growing concern that exposure to chemicals in the environment can disrupt the endocrine systems of wildlife and humans, causing reproductive problems or other adverse effects. The expression of many cytochrome P450s (CYPs) is under hormonal control, hence, levels of these enzymes can be affected by exposure to endocrine-disrupting chemicals. Previous research has reported that treatment of fish and other animals with the estrogenic and androgenic hormones 17beta-estradiol (E2) and testosterone (T) alters the P450 content or enzyme activities in the treated animals. However, the results of many of these studies are either incomplete or in disagreement and in most cases the effect on specific P450 forms has not been determined. Therefore, to better understand the effects of gonadal hormones on the expression of P450s and their associated enzyme activities, it was of interest to undertake a comprehensive investigation of the transcriptional and translational expression of three constitutive hepatic P450s in the rainbow trout (Oncorhynchus mykiss) following hormone exposure. Accordingly, juvenile trout were injected intraperitoneally with propylene glycol vehicle and the most active estrogenic and androgenic hormones E2 (3 mg/kg) or T (3 mg/kg) on days 1, 4, 7, 13, and 15 and euthanized on day 19. After treatment with E2, hepatic microsomes showed significantly lower levels (percentage of control) in total P450 contents (52%), lauric acid hydroxylase (32%), and 6beta-progesterone hydroxylase activities (27%), [(3)H]aflatoxin-DNA binding (31%), and the protein levels of individual cytochrome P450s (CYPs) LMC1 (CYP2M1), LMC2, (CYP2K1), and LMC5 (CYP3A27) (average for three isoforms a reduction to 29% of control values) with only minor differences between sexes. Treatment with T had either no effect or resulted in small increases in total P450 in males (42%), in lauric acid hydroxylase in females (24%), and in 6beta-progesterone hydroxylase activity in males (21%). Biological variabilities among fish were high and a polymorphic or new LMC2-like form was detected at about 52 kDa in some liver microsomal samples after exposure of fish to either hormone. Female liver RNAs were analyzed through Northern blots and an average decrease of 94% in CYP2 M1, CYP2K1, and CYP3A27 mRNA levels occurred in the E2-treated trout. In livers from T-treated trout, the changes of mRNA levels of CYP2M1 and CYP3A27 were negligible, but CYP2K1 mRNA level decreased by about 60%. Additional CYP2K1 cDNA hybridizable mRNAs were seen in some fish as faint bands at about 2.8 kb for both hormone treatments. Results of this study, therefore, indicated that E2 down-regulated while T produced small but variable effects on the hepatic mRNA/protein levels of CYP2K1, CYP2M1, and CYP3A27 in juvenile rainbow trout. This study, therefore, suggests that exposure of fish and other wildlife to environmental endocrine disruptors, especially estrogen mimics, can adversely affect a number of physiological processes through mechanisms involving altered levels of expression of specific P450 isozymes.

Aflatoxin B1↗

PubMed2000

ICAM-1-induced expression of proinflammatory cytokines in astrocytes: involvement of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways.

ICAM-1 is a transmembrane glycoprotein of the Ig superfamily involved in cell adhesion. ICAM-1 is aberrantly expressed by astrocytes in CNS pathologies such as multiple sclerosis, experimental allergic encephalomyelitis, and Alzheimer's disease, suggesting a possible role for ICAM-1 in these disorders. ICAM-1 has been shown to be important for leukocyte diapedesis through brain microvessels and subsequent binding to astrocytes. However, other functional roles for ICAM-1 expression on astrocytes have not been well elucidated. Therefore, we investigated the intracellular signals generated upon ICAM-1 engagement on astrocytes. ICAM-1 ligation by a mAb to rat ICAM-1 induced mRNA expression of proinflammatory cytokines such as IL-1alpha, IL-1beta, IL-6, and TNF-alpha. Examination of cytokine protein production revealed that ICAM-1 ligation results in IL-6 secretion by astrocytes, whereas IL-1beta and IL-1alpha protein is expressed intracellularly in astrocytes. The involvement of mitogen-activated protein kinases (MAPKs) in ICAM-1-mediated cytokine expression in astrocytes was tested, as the MAPK extracellular signal-regulated kinase (ERK) was previously shown to be activated upon ICAM-1 engagement. Our results indicate that ERK1/ERK2, as well as p38 MAPK, are activated upon ligation of ICAM-1. Studies using pharmacological inhibitors demonstrate that both p38 MAPK and ERK1/2 are involved in ICAM-1-induced IL-6 expression, whereas only ERK1/2 is important for IL-1alpha and IL-1beta expression. Our data support the role of ICAM-1 on astrocytes as an inflammatory mediator in the CNS and also uncover a novel signal transduction pathway through p38 MAPK upon ICAM-1 ligation.

Animals↗