Search PubMed⌕ Search

Biomedical subjects

Ken-ichiro Inoue

Publications and source records attributed to Ken-ichiro Inoue.

At least 19 recordsLinked to original sources
PubMed2006

Suppression of Th1 and Th2 immune responses in mice by Sinomenine, an alkaloid extracted from the chinese medicinal plant Sinomenium acutum.

The present study was designed to investigate the effect of sinomenine (SIN), an alkaloid extracted from Sinomenium acutum, on Th1 and Th2 immune responses in mice. For this investigation, mice were S. C. immunized with ovalbumin (OVA) emulsified with complete Freund's adjuvant (day 0). Varying doses of SIN were orally administered daily over a period of 21 days, commencing on day 0. On day 21, anti-OVA IgG and proliferative responses of spleen cells to the antigen were measured. Anti-OVA IgG2a and IFN-gamma were measured as indicators of Th1 immune responses and anti-OVA IgG1, IgE, and IL-5 as those of Th2 responses. TGF-beta was measured as an indicator of Th3 immune responses. The results showed that treatment with SIN was followed by decreases in anti-OVA IgG and the antigen-specific splenocyte proliferation. Production of all isotypes of antibodies including anti-OVA IgG2a, IgG1 and IgE as well as secretion of cytokines such as IFN-gamma and IL-5 was suppressed by SIN, although the suppression of anti-OVA IgG2a and IFN-gamma by the alkaloid appeared to be greater than that of anti-OVA IgG1, IgE, and IL-5. In addition, SIN enhanced the secretion of TGF-beta. These results suggest that SIN appears to have suppressive effects on both Th1 and Th2 immune responses. The results also suggest that Th1 responses may be more preferentially suppressed by the Sinomenium acutum-derived alkaloid compared to Th2 responses. TGF-beta may at least in part contribute to the suppression of Th1 as well as Th2 immune responses.

Administration, Oral↗
PubMed2006

Effects of organic chemicals derived from ambient particulate matter on lung inflammation related to lipopolysaccharide.

The effects of components of ambient particulate matter (PM) on individuals with predisposing respiratory disorders are not well defined. We have previously demonstrated that airway exposure to diesel exhaust particles (DEP) or organic chemicals (OC) extracted from DEP (DEP-OC) enhances lung inflammation related to bacterial endotoxin (lipopolysaccharide, LPS). The present study aimed to examine the effects of airway exposure to OC extracted from urban PM (PM-OC) on lung inflammation related to LPS. ICR mice were divided into four experimental groups that intratracheally received vehicle, LPS (2.5 mg/kg), PM-OC (4 mg/kg), or PM-OC + LPS. Lung inflammation, lung water content, and lung expression of cytokines were evaluated 24 h after intratracheal administration. LPS challenge elicited lung inflammation evidenced by cellular profiles of bronchoalveolar lavage fluid and lung histology, which was further aggravated by the combined challenge with PM-OC. The combination with PM-OC and LPS did not significantly exaggerate LPS-elicited pulmonary edema. LPS instillation induced elevated lung expression of interleukin-1beta, macrophage inflammatory protein-1alpha, macrophage chemoattractant protein-1, and keratinocyte chemoattractant, whereas the combined challenge with PM-OC did not influence these levels. All the results were consistent with our previous reports on DEP-OC. These results suggest that the extracted organic chemicals from PM exacerbate infectious lung inflammation. The mechanisms underlying the enhancing effects are not mediated via the enhanced local expression of proinflammatory cytokines.

Air Pollutants↗
PubMed2006

Role of interleukin-6 in fibrinolytic changes induced by lipopolysaccharide in mice.

We have recently demonstrated that interleukin (IL)-6 is protective against coagulatory and hemostatic disturbance and subsequent pulmonary hemorrhage induced by bacterial endotoxin, at least partly, via the inhibition of proinflammatory cytokines and chemokines using IL-6-null [IL-6(-/-)] mice and corresponding wild-type mice. Its role in fibrinolytic systems remains undefined, however. The present study elucidated the role of IL-6 in the activity of alpha(2)-plasmin inhibitor, an inhibitor of fibrinolysis, during inflammation induced by intraperitoneal administration of lipopolysaccharide in IL-6(-/-) and wild-type mice. Both IL-6(-/-) and wild-type mice were injected with vehicle or lipopolysaccharide (1 mg/kg). Seventy-two hours later, blood samples were collected and alpha(2)-plasmin inhibitor activity was examined. Lipopolysaccharide challenge induced significant enhancement of alpha(2)-plasmin inhibitor activity as compared with vehicle challenge in wild-type mice, but not in IL-6(-/-) mice. In the presence of lipopolysaccharide, the activity was significantly lower in IL-6(-/-) mice than that in wild-type mice. These results indicate that IL-6 can, at least partly, inhibit the lipopolysaccharide-enhanced fibrinolysis via the enhanced alpha2-plasmin inhibitor activity.

Animals↗
PubMed2006

Effects of volatile constituents of rosemary extract on lung inflammation induced by diesel exhaust particles.

Epidemiological and experimental studies have implicated that diesel exhaust particles are involved in increases in morbidity and mortality from lung diseases. Recently, we have demonstrated that rosmarinic acid, a polyphenolic liquid component in perilla, inhibits lung inflammation induced by diesel exhaust particles in vivo, partly through its antioxidative property. We have also shown the antioxidative activities of volatile constituents of rosemary extract, the gaseous component in perilla, in vitro. The purpose of this study was to evaluate the effects of intratracheal administration of volatile rosemary extract on lung inflammation induced by diesel exhaust particles. ICR mice were treated with intratracheal administration of volatile rosemary extract before intratracheal exposure to diesel exhaust particles. Twenty-four hr later, diesel exhaust particles exposure elicited lung inflammation characterized by the infiltration of neutrophils and eosinophils, which was confirmed by cellular profile of bronchoalveolar lavage fluid and histological examination. Diesel exhaust particles enhanced the protein expressions of interleukin-1beta, macrophage inflammatory protein-1alpha, macrophage chemoattractant protein-1, and keratinocyte chemoattractant in the lung. Pretreatment with rosemary extract significantly inhibited the diesel exhaust particles-induced lung inflammation. Rosemary extract treatment also suppressed the diesel exhaust particles-enhanced lung expression of macrophage inflammatory protein-1alpha, macrophage chemoattractant protein-1, and keratinocyte chemoattractant. These results suggest that intratracheal administration of rosemary extract can prevent lung inflammation induced by diesel exhaust particles. The preventive effect is mediated, at least partly, through the inhibition of the enhanced lung expressions of macrophage inflammatory protein-1alpha, macrophage chemoattractant protein-1, and keratinocyte chemoattractants.

Administration, Inhalation↗
PubMed2006

Di-(2-ethylhexyl) phthalate enhances atopic dermatitis-like skin lesions in mice.

Di-(2-ethylhexyl) phthalate (DEHP) has been widely used in polyvinyl chloride products and has become ubiquitous in the developed countries. DEHP reportedly displays an adjuvant effect on immunoglobulin production. However, it has not been elucidated whether DEHP is associated with the aggravation of atopic dermatitis. We investigated the effects of DEHP on atopic dermatitis-like skin lesions induced by mite allergen in NC/Nga mice. NC/Nga male mice were injected intradermally with mite allergen on their right ears. In the presence of allergen, DEHP (0, 0.8, 4, 20, or 100 microg) was administered by intraperitoneal injection. We evaluated clinical scores, ear thickening, histologic findings, and the protein expression of chemokines. Exposure to DEHP at a dose of 0.8-20 microg caused deterioration of atopic dermatitis-like skin lesions related to mite allergen; this was evident from macroscopic and microscopic examinations. Furthermore, these changes were consistent with the protein expression of proinflammatory molecules such as macrophage inflammatory protein-1alpha (MIP-1alpha) and eotaxin in the ear tissue in overall trend. In contrast, 100 microg DEHP did not show the enhancing effects. These results indicate that DEHP enhances atopic dermatitis-like skin lesions at hundred-fold lower levels than the no observed adverse effect level determined on histologic changes in the liver of rodents. DEHP could be at least partly responsible for the recent increase in atopic dermatitis.

Animals↗
PubMed2005

Role of metallothionein in coagulatory disturbance and systemic inflammation induced by lipopolysaccharide in mice.

Although metallothionein (MT) can be induced by inflammatory mediators, its roles in coagulatory disturbance during inflammation are poorly defined. We determined whether MT protects against coagulatory and fibrinolytic disturbance and systemic inflammation induced by intraperitoneal administration of lipopolysaccharide (LPS) in MT-I/II null (-/-) and wild-type (WT) mice. As compared with WT mice, MT (-/-) mice revealed significant prolongation of prothrombin and activated partial thromboplastin time, a significant increase in the levels of fibrinogen and fibrinogen/fibrin degradation products, and a significant decrease in activated protein C, after LPS treatment. LPS induced inflammatory organ damages in the lung, kidney, and liver in both genotypes of mice. The damages, including neutrophil infiltration, were more prominent in MT (-/-) mice than in WT mice after LPS treatment. In both genotypes of mice, LPS enhanced protein expression of interleukin (IL)-1beta, IL-6, granulocyte/macrophage-colony-stimulating factor, macrophage inflammatory protein (MIP)-1alpha, MIP-2, macrophage chemoattractant protein-1, and keratinocyte chemoattractant in the lung, kidney, and liver and circulatory levels of IL-1beta, IL-6, MIP-2, and KC. In overall trends, however, the levels of these proinflammatory proteins were greater in MT (-/-) mice than in WT mice after LPS challenge. Our results suggest that MT protects against coagulatory and fibrinolytic disturbance and multiple organ damages induced by LPS, at least partly, via the inhibition of the expression of proinflammatory proteins.

Animals↗
PubMed2005

Effects of nano particles on antigen-related airway inflammation in mice.

BACKGROUND: Particulate matter (PM) can exacerbate allergic airway diseases. Although health effects of PM with a diameter of less than 100 nm have been focused, few studies have elucidated the correlation between the sizes of particles and aggravation of allergic diseases. We investigated the effects of nano particles with a diameter of 14 nm or 56 nm on antigen-related airway inflammation. METHODS: ICR mice were divided into six experimental groups. Vehicle, two sizes of carbon nano particles, ovalbumin (OVA), and OVA + nano particles were administered intratracheally. Cellular profile of bronchoalveolar lavage (BAL) fluid, lung histology, expression of cytokines, chemokines, and 8-hydroxy-2'-deoxyguanosine (8-OHdG), and immunoglobulin production were studied. RESULTS: Nano particles with a diameter of 14 nm or 56 nm aggravated antigen-related airway inflammation characterized by infiltration of eosinophils, neutrophils, and mononuclear cells, and by an increase in the number of goblet cells in the bronchial epithelium. Nano particles with antigen increased protein levels of interleukin (IL)-5, IL-6, and IL-13, eotaxin, macrophage chemoattractant protein (MCP)-1, and regulated on activation and normal T cells expressed and secreted (RANTES) in the lung as compared with antigen alone. The formation of 8-OHdG, a proper marker of oxidative stress, was moderately induced by nano particles or antigen alone, and was markedly enhanced by antigen plus nano particles as compared with nano particles or antigen alone. The aggravation was more prominent with 14 nm of nano particles than with 56 nm of particles in overall trend. Particles with a diameter of 14 nm exhibited adjuvant activity for total IgE and antigen-specific IgG1 and IgE. CONCLUSION: Nano particles can aggravate antigen-related airway inflammation and immunoglobulin production, which is more prominent with smaller particles. The enhancement may be mediated, at least partly, by the increased local expression of IL-5 and eotaxin, and also by the modulated expression of IL-13, RANTES, MCP-1, and IL-6.

Air Pollutants↗
PubMed2005

Pulmonary exposure to diesel exhaust particles induces airway inflammation and cytokine expression in NC/Nga mice.

Although several studies have reported that diesel exhaust particles (DEP) affect cardiorespiratory health in animals and humans, the effect of DEP on animal models with spontaneous allergic disorders has been far less intensively studied. The Nc/Nga mouse is known to be a typical animal model for human atopic dermatitis (AD). In the present study, we investigated the effects of repeated pulmonary exposure to DEP on airway inflammation and cytokine expression in NC/Nga mice. The animals were randomized into two experimental groups that received vehicle or DEP by intratracheal instillation weekly for six weeks. Cellular profiles of bronchoalveolar lavage (BAL) fluid and expressions of cytokines and chemokines in both the BAL fluid and lung tissues were evaluated 24 h after the last instillation. The DEP challenge produced an increase in the numbers of total cells, neutrophils, and mononuclear cells in BAL fluid as compared to the vehicle challenge (P<0.01). DEP exposure significantly induced the lung expressions of interleukin (IL)-4, keratinocyte chemoattractant (KC), and macrophage inflammatory protein (MIP)-1alpha when compared to the vehicle challenge. These results indicate that intratracheal exposure to DEP induces the recruitment of inflammatory cells, at least partially, through the local expression of IL-4 and chemokines in NC/Nga mice.

Animals↗
PubMed2005

Effects of 15-deoxy-delta(12,14)-prostaglandin J2 on nuclear localization of GATA-3 in the murine lung in the presence of lipopolysaccharide.

15-Deoxy-delta(12, 14)-prostaglandin J2 (15d-PG J2) is a regulator of a nuclear transcriptional factor, peroxisome proliferator-activated receptor (PPAR)-gamma. A previous study has demonstrated that 15d-PG J2 enhanced acute lung injury induced by lipopolysaccharide (LPS) in mice. 15d-PG J2 induced mucin-producing cells in the bronchial epithelium, especially in the presence of LPS. The present study investigated the effects of 15d-PG J2 on the activation of GATA-3 and Signal Transducer and Activator of Transcription (STAT) 6, important transcriptional factors in mucus secretion, in the lung in the presence or absence of LPS. ICR mice were divided into 4 experimental groups that intratracheally received vehicle, lipopolysaccharide (LPS: 125 microg/kg), 15d-PG J2 (1 mg/kg), or 15d-PG J2 + LPS. The nuclear localization of GATA-3 and phosphorylated STAT 6 was evaluated 2 h after the intratracheal administration. 15d-PG J2 enhanced the nuclear localization of GATA-3 in the presence of LPS, whereas the nuclear localization of phosphorylated STAT 6 was not altered in the groups. These results suggest that the enhancing effects of 15d-PG J2 on the production of mucin-producing cells might be related, at least in part, to the activation of GATA-3.

Animals↗
PubMed2005

Effects of 15-deoxy-Delta12,14-prostaglandin J2 on the expression of Toll-like receptor 4 and 2 in the murine lung in the presence of lipopolysaccharide.

1. Previously, we have demonstrated that 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) enhances acute lung injury induced by lipopolysaccharide (LPS) in mice. The enhancement in acute lung injury by 15d-PGJ2 was concomitant with the enhanced expression of several pro-inflammatory cytokines in the lung. However, other underlying mechanisms of this enhancement remain to be elucidated. The present study investigated the effects of 15d-PGJ2 on the expression of Toll-like receptor (TLR) 4 and 2 in the lung in the absence or presence of LPS. 2. In the present study, ICR mice were divided into four experimental groups that received (intratracheally) vehicle, LPS (125 microg/kg), 15d-PGJ2 (1 mg/kg) or 15d-PGJ2 + LPS. The mRNA expression of both TLR4 and 2 in the lung was evaluated 4 h after intratracheal administration. 3. 15-Deoxy-Delta12,14-prostaglandin J2 enhanced the mRNA expression of both TLR4 and 2 in the presence of LPS. 4. These results suggest that the enhancing effects of 15d-PGJ2 on LPS-induced acute lung injury may be explained, at least in part, by its effect on the lung expression of TLR4 and 2.

Animals↗
PubMed2004

Anti-inflammatory and anti-allergic effect of rosmarinic acid (RA); inhibition of seasonal allergic rhinoconjunctivitis (SAR) and its mechanism.

The present study was undertaken to determine whether oral supplementation with rosmarinic acid (RA) is an effective intervention for patients with SAR. In addition, the anti-inflammatory mechanism of RA also estimated in the ear edema models. CLINICAL TRIAL: Patients were treated daily with RA (200 mg or 50 mg) or placebo for 21 days. Patients recorded symptoms daily and profiles of infiltrating cells and concentration of cytokines were measured in nasal lavage fluid. Compared to placebo, supplementation with RA resulted in a significant decrease in responder rates for each symptom. RA also significantly decreased the numbers of neutrophils and eosinophils in nasal lavage fluid. ANIMAL STUDY: Topical application RA showed anti-inflammatory activity 5-hours after 12-tetradecanoylphorbol 13-acetate (TPA) treatment with marked inhibition of neutrophil infiltration. Up regulation of ICAM-1, VCAM-1 cyclooxygenase-2 (COX-2), KC and MIP-2 by TPA were markedly reduced by pre-treatment with extract of perilla (PE) or RA. Reactive oxygen radical production detected as thiobarbituric acid reactive substance (TBARS), lipid peroxide (LPO) and 8-hydroxy-2'deoxyguanosine (8OH-dG), by double treatment of TPA was reduced by pretreatment with PE or RA. RA is an effective intervention for SAR that is mediated by inhibition of PMNL infiltration. This effect of RA is due to two independent mechanisms: inhibition of the inflammatory response and scavenging of ROS.

Animals↗
PubMed2004

Effects of 15-deoxy-delta12,14-prostaglandin J2 on the cyclooxygenase-2 expression in the murine lung in the presence of lipopolysaccharide.

A previous study has demonstrated that 15-deoxy-delta12,14-prostaglandin J2 (15d-PG J2) enhanced acute lung injury induced by lipopolysaccharide (LPS) in mice. The enhancement in acute lung injury by 15d-PG J2 was concomitant with the enhanced expression of interleukin-1beta and chemokines in the lung. However, other underlying mechanisms of this enhancement remain to be elucidated. Cyclooxygenase (COX)-2 has been reported to be involved in enhanced pulmonary permeability during acute lung injury. This study investigated the effects of 15d-PG J2 on COXs expressions in the lung in the presence or absence of LPS. ICR mice were divided into 4 experimental groups that intratracheally received vehicle, lipopolysaccharide (LPS: 125 microg/kg), 15d-PG J2 (1 mg/kg), or 15d-PG J2 + LPS. The expression of mRNA for both COX-1 and -2 in the lung was evaluated 4 h after the intratracheal administration. 15d-PG J2 enhanced the COX-2 mRNA expression in the presence of LPS. In contrast, 15d-PG J2 did not affect the COX-1 expression. These results suggest that the enhancing effects of 15d-PG J2 on LPS-induced acute lung injury might be explained, at least in part, by those on the lung expression of COX-2.

Animals↗
PubMed2004

A novel water-soluble vitamin E derivative prevents acute lung injury by bacterial endotoxin.

1. Various chemokines, such as keratinocyte chemoattractant (KC), macrophage inflammatory protein (MIP)-1alpha and macrophage chemoattractant protein (MCP)-1, are involved in the pathogenesis of acute lung injury induced by bacterial endotoxin (lipopolysaccharide; LPS). Oxidative stress is an important regulator of the expression of these chemokines, whereas vitamin E protects against LPS-induced insults. In the present study, we determined the effects of 2-(alpha-D-glucopyranosyl) methyl-2,5,7,8-tetramethylchroman-6-ol (TMG), a novel water-soluble vitamin E derivative with excellent anti-oxidant activity, on acute lung injury induced by intratracheal instillation of LPS (125 micro g/kg) in mice. 2. When TMG was administered intratracheally and intravenously (0.1, 1.0 or 10 mg/kg), it dose-dependently decreased the infiltration of neutrophils into bronchoalveolar lavage fluid after LPS challenge. 3. Histological examination showed that treatment with TMG ameliorated the LPS-induced infiltration of neutrophils into the lungs. Furthermore, TMG attenuated the LPS-induced increase in pulmonary expression of KC, MIP-1alpha and MCP-1 at both the transcriptional and translational levels. 4. These results indicate that TMG is a possible treatment for acute lung injury, especially that caused by Gram-negative bacteria. The therapeutic effect of TMG may be mediated, at least in part, by suppression of the local expression of chemokines, possibly through its strong anti-oxidant activity.

Animals↗
PubMed2004

Protective role of interleukin-6 in coagulatory and hemostatic disturbance induced by lipopolysaccharide in mice.

Although the role of interleukin (IL)-6 in inflammatory diseases has been previously examined, its role in hemostasis, fibrinolysis, and coagulation during inflammation remains to be established. The present study elucidated the role of IL-6 in hemostatic and coagulatory changes during severe inflammation induced by intraperitoneal administration of lipopolysaccharide (LPS: 1 mg/kg) using IL-6 null (-/-) mice. After LPS challenge, IL-6 (-/-) mice revealed significant prolongation of prothrombin time and activated partial thromboplastin time and a significant decrease in platelet counts as compared with wild type mice. LPS treatment induced marked pulmonary hemorrhage with neutrophilic inflammation in IL-6 (-/-) mice, in contrast, only mild neutrophilic infiltration in WT mice confirmed by macroscopic and histological findings. The protein levels of proinflammatory mediators, such as IL-1 beta, macrophage inflammatory protein (MIP)-1 alpha, MIP-2, macrophage chemoattractant protein-1, granulocyte/macrophage-colony-stimulating factor, and keratinocyte chemoattractant in the lungs were significantly greater in IL-6 (-/-) mice than in WT mice after LPS challenge. These results directly indicate that IL-6 is protective against coagulatory and hemostatic disturbance and subsequent pulmonary hemorrhage induced by bacterial endotoxin, at least partly, via the modulation of proinflammatory processes.

Animals↗
PubMed2004

Extract of Perilla frutescens enriched for rosmarinic acid, a polyphenolic phytochemical, inhibits seasonal allergic rhinoconjunctivitis in humans.

Extract of Perilla frutescens enriched for rosmarinic acid, a polyphenolic phytochemical, suppresses allergic immunoglobulin responses and inflammation caused by polymorphonuclear leukocytes (PMNL) in mice. However, few placebo-controlled clinical trials have examined the efficacy and safety of polyphenolic phytochemicals for treatment of allergic inflammatory diseases in humans. The present study determined whether oral supplementation with rosmarinic acid is an effective intervention for patients with seasonal allergic rhinoconjunctivitis (SAR). In this 21-day, randomized, double-blind, age-matched, placebo-controlled parallel group study, patients with mild SAR were treated daily with extract of Perilla frutescens enriched for rosmarinic acid (200 mg [n=10] or 50 mg [n=9]) or placebo (n=10). Patients recorded symptoms daily in a diary. Profiles of infiltrating cells and concentrations of eotaxin, IL-1beta, IL-8, and histamine were measured in nasal lavage fluid. Serum IgE concentrations and routine blood tests were also examined. As compared with placebo supplementation, supplementation with extract of Perilla frutescens enriched for rosmarinic acid resulted in a significant increase in responder rates for itchy nose, watery eyes, itchy eyes, and total symptoms (P<0.05). Active treatment significantly decreased the numbers of neutrophils and eosinophils in nasal lavage fluid (P<0.05 vs. placebo). Patients reported no adverse events, and no significant abnormalities were detected in routine blood tests. In conclusion, extract of Perilla frutescens enriched for rosmarinic acid can be an effective intervention for mild SAR at least partly through inhibition of PMNL infiltration into the nostrils. Use of this alternative treatment for SAR might reduce treatment costs for allergic diseases.

Adult↗
PubMed2004

Nitrogen dioxide air pollution near ambient levels is an atherogenic risk primarily in obese subjects: a brief communication.

Ambient exposure to nitrogen dioxide, a critical air pollutant in developed countries, is positively associated with cardiovascular mortality and morbidity. Although its cardiovascular effects are predominantly shown in patients with high risk of atherogenesis, no studies have elucidated whether daily exposure to nitrogen dioxide air pollution enhances atherogenic metabolisms, primarily in obese subjects who are susceptible to atherogenesis and subsequent cardiovascular diseases. We used male Otsuka Long-Evans Tokushima Fatty (OLETF) rats as obese subjects and Long-Evans Tokushima (LETO) rats as nonobese controls. The animals were continuously exposed to nitrogen dioxide at a concentration of 0, 0.16, 0.8, or 4.0 ppm from 8 weeks of age through 32 weeks. At 40 weeks of age, levels of body weight, triglyceride, and total cholesterol were significantly greater in the OLETF rats than in the LETO rats. A ratio of high-density lipoprotein (HDL) to total cholesterol was significantly smaller in the former than in the latter. In the LETO rats, nitrogen dioxide exposure significantly decreased only the levels of HDL as compared with clean air exposure. In the OLETF rats, however, nitrogen dioxide exposure at a concentration of 0.16 ppm significantly elevated triglyceride concentration and decreased the ratio of HDL to total cholesterol as well as the levels of HDL. Nitrogen dioxide air pollution near ambient levels is an atherogenic risk primarily in obese subjects.

Air Pollution↗
PubMed2004

Complementary DNA microarray analysis in acute lung injury induced by lipopolysaccharide and diesel exhaust particles.

We have recently shown that diesel exhaust particles (DEP) synergistically enhance acute lung injury related to lipopoly-saccharide (LPS) in mice. The present study used cDNA microarray to elucidate the effects of DEP on the global pattern of LPS-related gene expression in the murine lung. The number of genes upregulated >/=2-fold as compared with their expression levels in the vehicle group was greater in the LPS group than in other groups, but treatment with DEP and LPS dramatically increased the number of the genes upregulated >/=6-fold. In particular, gene expression of metallothionein-1 and -2, S100 calcium-binding protein A9, lipocalin 2, and small inducible cytokine B family member 10 was higher by >/=20-fold in the DEP + LPS group than in the vehicle group. These results were concomitant with those obtained by real-time reverse transcription-polymerase chain reaction analysis in the overall trend. Our findings suggest that intense, focused expression of genes such as S100 calcium-binding protein A9, lipocalin 2, and small inducible cytokine B family member 10 relates to the synergistic aggravation of acute lung injury by LPS and DEP rather than weak, broad expression of various genes by exposure of LPS alone.

Animals↗