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Hirohisa Takano

Publications and source records attributed to Hirohisa Takano.

16 recordsLinked to original sources
PubMed2003

Rosmarinic acid inhibits lung injury induced by diesel exhaust particles.

Epidemiological and experimental studies have suggested that diesel exhaust particles (DEP) may be involved in recent increases in lung diseases. DEP has been shown to generate reactive oxygen species. Intratracheal instillation of DEP induces lung inflammation and edema in mice. Rosmarinic acid is a naturally occurring polyphenol with antioxidative and anti-inflammatory activities. We investigated the effects of rosmarinic acid on lung injury induced by intratracheal administration of DEP (500 microg/body) in mice. Oral supplementation with administration of rosmarinic acid (2 mg/body for 3 d) inhibited DEP-induced lung injury, which was characterized by neutrophil sequestration and interstitial edema. DEP enhanced the lung expression of keratinocyte chemoattractant (KC), interleukin-1beta, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1alpha, which was inhibited by treatment with rosmarinic acid. DEP enhanced expression of iNOS mRNA and formation of nitrotyrosine and 8-OHdG in the lung, which was also inhibited by rosmarinic acid. These results suggest that rosmarinic acid inhibits DEP-induced lung injury by the reduction of proinflammatory molecule expression. Antioxidative activities of rosmarinic acid may also contribute to its protective effects.

Administration, Oral↗
PubMed2003

Differences in airway-inflammation development by house dust mite and diesel exhaust inhalation among mouse strains.

Three mouse strains (BALB/c, ICR, and C3H/He) were injected intratracheally with house dust mites (Der f) four times at 2-week intervals during exposure to diesel exhaust (DE) or clean air for 8 weeks. Der f treatment caused eosinophilic inflammation and proliferation of goblet cells in the airways of the three strains. DE + Der f caused a further increase of eosinophils in BALB/c and ICR mice, but not in C3H/He mice. DE + Der f significantly increased interleukin (IL)-5; regulated on activation, normal T cell expressed, and presumably secreted (RANTES); eotaxin, monocyte chemotactic protein-1 (MCP-1); and macrophage-inflammatory protein-1 alpha (MIP-1 alpha) in all three strains. However, the protein of IL-5 decreased more in C3H/He mice treated with DE + Der f than in mice treated with Air + Der f. The levels of IL-5 in lung tissues corresponded to the pathological changes by Der f and/or DE treatment. The levels of MCP-1 and MIP-1 alpha in the three strains corresponded to the accumulation of lymphocytes in the airway. The adjuvant effect of DE on IgG1 production was observed in the ICR and C3H/He mice. These results suggest that the murine strain differences in the production of eosinophilic airway inflammation by DE + Der f is related to differences in local expression of IL-5, eotaxin, and IgG1 production. The enhancing effects of DE exposure may be mediated mainly by local IL-5.

Administration, Inhalation↗
PubMed2003

Effect of the nonsteroidal anti-inflammatory drug indomethacin on Th1 and Th2 immune responses in mice.

The present study was undertaken to study the effect of the nonsteroidal anti-inflammatory drug indomethacin on Th1 and Th2 immune responses. For this study, mice were immunized by s.c. injection of ovalbumin (OVA) emulsified with complete Freund's adjuvant into the base of the tail (day 0). Varying doses of indomethacin were orally administrated daily from days 0 to 20. On day 21, anti-OVA IgG2a and interferon-gamma as an indicator of Th1 responses and anti-OVA IgG1 and interleukin-10 as that of Th2 responses were measured. The results showed that treatment with indomethacin was followed by decreases in OVA-specific IgG and proliferation of spleen cells to the antigen. Indomethacin inhibited both Th1 and Th2 responses, although the nonsteroidal anti-inflammatory drug suppressed the former more effectively than the latter. Administration of indomethacin resulted in suppression of antigen (OVA)-induced arthritis that was associated with inhibition of anti-OVA IgG2a but not IgG1 production. These results suggest that nonsteroidal anti-inflammatory drugs may downregulate Th1 and, to a lesser extent, Th2 immune responses.

Animals↗
PubMed2003

Effects of bisphenol A on antigen-specific antibody production, proliferative responses of lymphoid cells, and TH1 and TH2 immune responses in mice.

1. We investigated the effect of bisphenol A (BPA), which binds estrogen receptors, on immune responses including production of antigen-specific antibodies, proliferative responses of lymphoid cells, and Th1 and Th2 responses. 2. For this investigation, mice were p.o. given varying doses including 3, 30, 300, and 3000 micro g kg(-1) of BPA immediately after immunization with hen egg lysozyme (HEL) (day 0) and then daily by day 20. On day 21, anti-HEL IgG antibodies in sera and proliferative responses of spleen cells to the antigen were measured. Anti-HEL IgG2a antibodies and IFN-gamma secreted from splenic lymphocytes were also measured as indicators of Th1 immune responses, while anti-HEL IgG1 antibodies and IL-4, as those of Th2 responses. 3. The results showed that treatment with 3000 micro g kg(-1) of BPA was followed by a significant increase in anti-HEL IgG as well as the antigen-specific cell proliferation. Anti-HEL IgG2a production and IFN-gamma secretion were significantly enhanced in mice treated with 300 and 30 micro g kg(-1) of BPA, respectively, while anti-HEL IgG1 production and IL-4 secretion were augmented in animals given 3000 and 300 micro g kg(-1) of the chemical, respectively. 4. Augmentation of these immune responses was also observed in mice exposed to 0.3-30 micro g kg(-1) of estradiol, although Th1 responses appeared to be more sensitive to the sex hormone than Th2 responses. 5. These results suggest that BPA may play a role in augmenting immune responses, especially Th1 responses.

Animals↗
PubMed2002

Enhancement of antigen-induced eosinophilic inflammation in the airways of mast-cell deficient mice by diesel exhaust particles.

The present study was conducted to clarify the involvement of mast cells in the exacerbating effect of diesel exhaust particles (DEP) toward allergic airway inflammation and airway hyperresponsiveness (AHR). Airway inflammation by the infiltration of cosinophils with goblet cell proliferation and AHR, as well as by the production of antigen-specific IgG1 and IgE, in plasma were examined using mast cell-deficient mice (W/W(v)) and normal mice (W/W(+)). Both groups of mice received ovalbumin (OVA) or OVA+DEP intratracheally. The eosinophilic airway inflammation and goblet cell proliferation promoted by OVA were significantly greater in W/W(+) than in W/W(v). A similar result was observed in AHR, but was not significant among both groups of mice. DEP enhanced OVA induced-allergic airway inflammation, goblet cell proliferation, and development of AHR in W/W(v), but not in W/W(+). DEP decreased production of antigen-specific IgG1 and IgE in both groups of mice. Mast cells were observed in the submucosal layer of the main bronchus in W/W(v). The number of mast cells was significantly decreased by OVA treatment. The results indicate that mast cells are not necessary to enhance airway damage and development of AHR in W/W(v) by DEP. However, mast cells may be required for the OVA-induced cosinophilic inflammation, airway damage with goblet cell proliferation, and AHR in W/W(+).

Animals↗
PubMed2002

Diesel exhaust particles enhance lung injury related to bacterial endotoxin through expression of proinflammatory cytokines, chemokines, and intercellular adhesion molecule-1.

Epidemiologic studies demonstrate acute and serious adverse effects of particulate air pollution on respiratory health, especially in people who are susceptible to bacterial infection. However, the underlying mechanism remains to be elucidated. To provide experimental evidence for the epidemiologic data, we determined the effects of diesel exhaust particles (DEP), major participants in particulate pollutants, on lung injury related to bacterial endotoxin in mice. Intratracheal instillation of DEPs synergistically enhanced lung injury related to endotoxin from gram-negative bacteria, which was characterized by neutrophil sequestration, interstitial edema, and alveolar hemorrhage. In the presence of endotoxin, DEPs further activated the nuclear translocation of p65 subunit of nuclear factor-kappaB (NF-kappaB) in the lung and increased the lung expression of intercellular adhesion molecule-1, interleukin-1beta, macrophage chemoattractant protein-1, keratinocyte chemoattractant (KC), macrophage inflammatory protein-1alpha, and Toll-like receptors. DEPs given alone increased the lung expression of Toll-like receptor 4 and the nuclear localization of p50 subunit of NF-kappaB. The combined exposure to DEPs and endotoxin decreased nuclear localization of CCAAT/enhancer binding protein beta. These results provide the first experimental evidence that DEPs enhance neutrophilic lung inflammation related to bacterial endotoxin. The enhancement is mediated by the induction of proinflammatory molecules, likely through the expression of Toll-like receptors and the activation of p65-containing dimer(s) of NF-kappaB, such as p65/p50.

Analysis of Variance↗
PubMed2002

Lung expression of cytochrome P450 1A1 as a possible biomarker of exposure to diesel exhaust particles.

Polycyclic aromatic hydrocarbons (PAH) and reactive oxygen species (ROS) derived from diesel exhaust particles (DEP) are implicated in the pathophysiology of respiratory diseases. Cytochrome P450 (Cyp) 1A1 can be induced by several kinds of PAH and produce ROS. We determined whether acute inhalation exposure to DEP induced the expression of Cyp 1A1 in murine lung. Intratracheal instillation of DEP dose-dependently increased the lung expression of Cyp 1A1 at the levels of both mRNA and protein, whereas DEP decreased expression in the lung of aryl hydrocarbon receptors in a dose-dependent manner. In contrast, charcoal particles as the control did not affect the expression of these molecules. These results suggest that the lung expression of Cyp 1A1 can be a biomarker of acute inhalation exposure to DEP and may be implicated in an accelerated production of ROS and the subsequent aggravation of lung injury.

Animals↗
PubMed2002

Effect of diesel exhaust particle extracts on induction of oral tolerance in mice.

We examined the effect of diesel exhaust particle (DEP) extracts on oral tolerance in mice. For this examination, a single DEP sample was consecutively extracted with hexane (HEX-DEP), benzene (BEN-DEP), dichloromethane (DIC-DEP), methanol (MET-DEP), and 1 M ammonia (AMM-DEP). Residues unextracted (UNE-DEP) with the last extraction solvent 1 M ammonia were also used to test their ability to induce oral tolerance. To immunize mice, hen egg lysozyme (HEL) emulsified with an equal volume of CFA was injected sc (day 0). Oral tolerance was induced by feeding 10 mg HEL on days -5, -4, -3, -2, and -1. DEP, each DEP extract, and UNE-DEP were intranasally administered immediately after each feeding of HEL. The results showed that oral administration of HEL markedly suppressed production of anti-HEL IgG antibodies as well as proliferative responses of spleen cells to HEL. The suppression of anti-HEL IgG antibody production and the cell proliferation by the oral antigen was significantly blocked by DEP, DIC-, AMM-, and UNE-DEP. Neither HEX-, BEN-, nor MET-DEP modulated the orally induced suppression of these immune responses. When the levels of anti-HEL IgG2a antibodies and IFN-gamma (Th1 responses) and anti-HEL IgG1 antibodies and IL-4 (Th2 responses) were determined, DEP and DIC-DEP diminished the suppression of both Th1 and Th2 responses observed following oral administration of HEL. In contrast, UNE- and AMM-DEP prevented the reduction of Th1 but not Th2, and Th2 but not Th1 oral tolerance, respectively. Thus, UNE-DEP appears to contain compounds that block induction of Th1 but not Th2 oral tolerance, whereas AMM-DEP have compounds that abrogate induction of Th2 but not Th1 oral tolerance. DIC-DEP, as well as DEP, appear to contain components that block induction of both Th1 and Th2 oral tolerance. As oral tolerance is thought to play a critical role in preventing Th1 as well as Th2 food allergy, the blockade of oral tolerance by these DEP extracts suggests that DEP may contain compounds different in hydrophobicity associated with the cause of such adverse immunologic responses to food proteins.

Animals↗
PubMed2002

A novel water-soluble vitamin E derivative, 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol, protects against acute lung injury and mortality in endotoxemic rats.

Satisfactory therapy for acute lung injury related to endotoxemia remains to be established. However, in vivo antioxidant treatment with N-acetylcysteine reportedly suppresses acute lung injury and proinflammatory cytokine production induced by endotoxin (lipopolysaccharide, LPS). In addition, intrinsic vitamin E is protective against LPS-induced insults. We determined the effects of a novel water-soluble vitamin E derivative, 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol (TMG), on acute lung injury and mortality induced by LPS in rats. Intravenous injection of TMG (4 or 40 mg/kg) effectively decreased mortality and prevented the increased alveolar permeability and pulmonary edema that were caused by intravenous injection of LPS (20 mg/kg). Treatment with TMG decreased the enhanced lung expression of TNF-alpha caused by LPS. TMG also suppressed the sequestration of neutrophils in the lung induced by LPS. These results indicate that TMG is a possible therapeutic agent for acute lung injury and mortality, especially that caused by gram-negative bacteria. The therapeutic effects could be mediated at least partly through suppression of the increased expression of TNF-alpha and neutrophil sequestration in the lung that are caused by LPS.

Acute Disease↗
PubMed2002

Murine strain differences in airway inflammation induced by diesel exhaust particles and house dust mite allergen.

BACKGROUND: Differences in allergic airway inflammation induced by ovalbumin (OVA) + diesel exhaust particles (DEP) in various murine strains have already been reported. However, there is no report that different murine strains respond differently towards house dust mites or DEP, which are known to aggravate allergic asthma. METHODS: The Dermatophagoides farinae allergens Der f (1 microg) or Der f (1 microg) + DEP (50 microg) were administered intratracheally to two different mouse strains (CBA/JN and C57BL/6N). Histological changes in the lung tissues, asthma-relevant cytokines in the lungs, and allergen-specific immunoglobulins in plasma were investigated. RESULTS: Der f treatment led to the proliferation of goblet cells, production of mucus plugs, and the recruitment of eosinophils and lymphocytes to the airways of the mice. The manifestation of the airway inflammation in the C57BL/6N mouse was much greater than in the CBA/JN mouse. The protein levels of interleukin (IL)-4 and IL-5, regulated on activation, normal T cell expressed, and presumably secreted (RANTES), and eotaxin in the lung tissue of C57BL/6N mice were higher than those in CBA/JN mice by a factor of 1.26 (IL-4), 5.26 (IL-5), 2.07 (RANTES) and 3.27 (eotaxin). DEP aggravated the manifestations of the eosinophilic inflammation in CBA/JN mice through goblet cell proliferation. However, the exact effect of DEP could not be evaluated in C57BL/6N because of its severe enhancement of the inflammation. DEP enhanced the local expression of IL-5, RANTES, and eotaxin in the CBA/JN mouse, and consequently triggered an increased IgG1 production in both strains. Allergen-specific IgE antibodies were lower than 1 titer in both mice. CONCLUSION: The murine strain differences in the pathogenesis of allergic airway disease caused by mite allergen might be related to the local expression of the cytokines we screened. The aggravating effect of DEP may be mediated by an increase in the local expression of IL-5, RANTES, eotaxin, and the production of an antigen specific to IgG1.

Animals↗
PubMed2002

Formaldehyde enhances mite allergen-induced eosinophilic inflammation in the murine airway.

Formaldehyde (FA) irritates the skin, eyes, and respiratory system and is considered to be a typical air pollutant. We investigated the effects of FA on the manifestations of airway inflammation caused by a house-dust mite allergen (Der f). ICR mice were exposed to 0.5% FA mist once a week for 4 weeks. The mice were sensitized intraperitoneally with Der f and ALUM prior to FA exposure. After the last FA exposure, theywere instilled intratracheally with Der f. The airway inflammation was subsequently examined. The Der f-specific IgG1 and IgE in plasma as well as the asthma-relevant cytokines in the lungs were measured. We found an increase in the plasma IgG1 production of and in the expression of interleukin-5 (IL-5) and regulated on activation, normal T cell expressed, and presumably secreted (RANTES) in the lungs of mice treated with Der f. The FA exposure enhanced the manifestation ofthe histopathological changes caused by Der f. This observation corresponded to the enhancement of IL-5 and RANTES production. However, the antigen-specific IgG1 antibody did not increase. The IL-4 cytokine level induced by Der fwith or without FA was the same as that of the control. IL-2, granulocyte macrophage-colony stimulating factor (GM-CSF), and antigen-specific IgE were not detected. FA exposure enhanced the eosinophilic airway inflammation and the proliferation of goblet cells, which were induced by a mite allergen responsible for the increased local expression of IL-5 and RANTES.

Allergens↗