International immunopharmacology
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Int. Immunopharmacol. · Jun 2008
Heme oxygenase-1 upregulation significantly inhibits TNF-alpha and Hmgb1 releasing and attenuates lipopolysaccharide-induced acute lung injury in mice.
The present study was designed to investigate whether administration of CoPPIX, an HO-1 inducer, could significantly inhibit TNF-alpha and Hmgb1 expression and thus attenuate the acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice. Acute lung injury was induced successfully by intratracheal administration of LPS (0.5 mg/kg) in male BALB/c mice. CoPPIX or ZnPPIX (an HO-1 inhibitor) was administered to mice 24 h prior to LPS exposure. ⋯ In addition, CoPPIX was also believed to have down-regulated the expression of LPS-induced proinflammatory cytokines, including early proinflammatory cytokine TNF-a, and late proinflammatory cytokine Hmgb1. In contrast, no obvious difference was observed between the ZnPPIX group and the LPS group. These findings demonstrate the significant protection of CoPPIX against LPS-induced ALI, and the effect mechanism of CoPPIX was associated with decreasing the expression of TNF-a and Hmgb1.
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Int. Immunopharmacol. · May 2008
Changes in HLA-DR expression, cytokine production and coagulation following endotoxin infusion in healthy human volunteers.
The infusion of a low dose of endotoxin into healthy subjects triggers a complex inflammatory response but the intricacies of which, despite extensive research, are still being unraveled. Nine healthy male volunteers received a dose of 30 Units endotoxin/kg bodyweight as an intravenous bolus. Following endotoxin infusion the concentration of TNF-alpha in their serum rapidly increased within 30 min, peaked after 1-2 h and returned to baseline by 4 h. ⋯ This was in contrast to endotoxin-induced changes in white blood cell (WBC) numbers, which dropped rapidly (at 2-3 h) while HLA-DR levels were stable and then peaked during the nadir in HLA-DR expression (8 h). Furthermore, endotoxin injection caused activation of both fibrinolytic and coagulation pathways. Thus, endotoxin infusion results in complex changes in HLA-DR expression, production of pro- and anti-inflammatory cytokines and activation of coagulation.
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Int. Immunopharmacol. · May 2008
Establishing the phenotype in novel acute and chronic murine models of allergic asthma.
Allergic asthma is a chronic disease of the airways, with superimposed acute inflammatory episodes which correspond to exacerbations of asthma. Two novel models of allergic asthma have been developed in mice receiving the same allergen sensitisation, but with acute or chronic allergen exposures, the latter to mimic the human situation more closely. Ovalbumin-sensitised mice were challenged by ovalbumin inhalation twice on the same day for the acute model, and 18 times over a period of 6 weeks for the chronic model. ⋯ Airway hyperresponsiveness to methacholine was observed 24 h after challenge in both models. The acute model had higher levels of eosinophilia, whereas the chronic model showed hyperresponsiveness to lower doses of methacholine and had higher levels of total IgE and ovalbumin-specific IgG antibodies. Both novel murine models of allergic asthma bear a close resemblance to human asthma, each offering particular advantages for studying the mechanisms underlying asthma and for evaluating existing and novel therapeutic agents.
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Int. Immunopharmacol. · Apr 2008
A pinusolide derivative, 15-methoxypinusolidic acid from Biota orientalis inhibits inducible nitric oxide synthase in microglial cells: implication for a potential anti-inflammatory effect.
The inhibitory effect of 15-methoxypinusolidic acid (15-MPA) isolated from Biota orientalis (Cupressaceae) on lipopolysaccharide (LPS)-induced inflammation in microglial BV2 cells was investigated. 15-MPA significantly reduced the expression of inducible nitric oxide synthase (iNOS), the activity of iNOS, and the production of nitric oxide (NO) in LPS-stimulated BV2 cells. In addition, 15-MPA significantly suppressed the expressions of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and cyclooxygenase (COX)-2. ⋯ LPS-activated p38 MAPK, extracellular signal-regulated kinase (ERK)-1/2, and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) were not affected by 15-MPA. Taken together, this study demonstrates that 15-MPA inhibits LPS-induced iNOS expression and NO production, independent on MAPK and NF-kappaB, suggesting a potential anti-inflammatory effect of the compound on microglial cells.
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Int. Immunopharmacol. · Mar 2008
Polysaccharides from Antrodia camphorata mycelia extracts possess immunomodulatory activity and inhibits infection of Schistosoma mansoni.
Antrodia camphorata (AC) is a commonly used fungus in folk medicine for the treatment of viral hepatitis and cancer. AC polysaccharides (AC-PS) are reported to possess anti-inflammatory, anti-hepatitis B virus, and anticancer activities. In this study, we tested the in vivo effect of AC-PS on immune function by evaluating cytokine expression; on immunomodulation, by evaluating spleen cells; and on Schistosoma mansoni infection in mice. ⋯ The CD4+/CD8+ ratio and number of B cells among splenocytes were also augmented. By using a disease model of parasitic infection, we found that AC-PS treatment inhibited S. mansoni infection in BALB/c mice. AC-PS appears to modulate the immune system of mice and has potential for preventing S. mansoni infection.