LTD₄ induces HB-EGF-dependent CXCL8 release through EGFR activation in human bronchial epithelial cells

Airway epithelial cells release proinflammatory mediators that may contribute to airway remodeling and leukocyte recruitment. We explored the hypothesis that leukotriene D? (LTD?) may trigger the release of proremodeling factors through activation of the EGF receptor (EGFR). We particularly focused on the effects of LTD? on release of heparin-binding EGF-like factor (HB-EGF) and IL-8 (CXCL8), a potent neutrophil chemoattractant that may be released downstream of EGFR activation. To address this hypothesis, both primary (NHBE) and transformed bronchial human epithelial cells (BEAS-2B) were grown on an air-liquid interface and stimulated with LTD?. HB-EGF and CXCL8 were evaluated by ELISA in cell culture supernatants. To explore the EGFR signaling pathway, we used a broad-spectrum matrix metalloproteinase (MMP) inhibitor, GM-6001, two selective EGFR tyrosine kinase inhibitors, AG-1478 and PD-153035, an HB-EGF neutralizing antibody, and a specific small interfering RNA (siRNA) against the EGFR. Expression of the CysLT? cysteinyl leukotriene receptor was demonstrated by RT-PCR and immunocytochemistry in both BEAS-2B and NHBE cells. Four hours after stimulation with LTD?, HB-EGF and CXCL8 were significantly increased in cell culture supernatant. GM-6001 and montelukast, a specific CysLT? receptor antagonist, blocked the LTD?-induced increase in HB-EGF. All inhibitors/antagonists decreased LTD?-induced CXCL8 release. siRNA against EGFR abrogated CXCL8 release following stimulation with LTD? and exogenous HB-EGF. These findings suggest LTD? induced EGFR transactivation through the release of HB-EGF in human bronchial epithelial cells with downstream release of CXCL8. These effects may contribute to epithelial-mediated airway remodeling in asthma and other conditions associated with cysteinyl leukotriene release.     

ICOS-Expressing CD4 T Cells Induced via TLR4 in the Nasal Mucosa Are Capable of Inhibiting Experimental Allergic Asthma

Modulation of adaptive immune responses via the innate immune pattern recognition receptors, such as the TLRs, is an emerging strategy for vaccine development. We investigated whether nasal rather than intrapulmonary application of Protollin, a mucosal adjuvant composed of TLR2 and TLR4 ligands, is sufficient to elicit protection against murine allergic lower airway disease. Wild-type, Tlr2(-/-), or Tlr4(-/-) BALB/c mice were sensitized to a birch pollen allergen extract (BPEx), then received either intranasal or intrapulmonary administrations of Protollin or Protollin admixed with BPEx, followed by consecutive daily BPEx challenges. Nasal application of Protollin or Protollin admixed with BPEx was sufficient to inhibit allergic lower airway disease with minimal collateral lung inflammation. Inhibition was dependent on TLR4 and was associated with the induction of ICOS in cells of the nasal mucosa and on both CD4(+)Foxp3(+) and CD4(+)Foxp3(-) T cells of the draining lymph nodes (LNs), as well as their recruitment to the lungs. Adoptive transfer of cervical LN CD4(+)ICOS(+), but not CD4(+)ICOS(-), cells inhibited BPEx-induced airway hyperresponsiveness and bronchoalveolar lavage eosinophilia. Thus, our data indicate that expansion of resident ICOS-expressing CD4(+) T cells of the cervical LNs by nasal mucosal TLR4 stimulation may inhibit the development of allergic lower airway disease in mice.     

Annual cycles of body weight in the Namie's frosted bat, Vespertilio superans superans

In order to elucidate the circannual cycles of fat deposition and depletion in hibernating bats, annual rhythm of body weight was examined in Vespertilio superans superans under a variety of environmental conditions. Under near natural conditions, adult females put on weight rapidly from October to November. The laboratory born subadult females kept in constant darkness at warm temperature gained weight at the same time as the adults. The length of weight cycle was about 10 months in adult females kept in 14 L : 10 D at about 24°C. These results suggest that cycles of fat deposition and loss are controlled by a modifiable endogenous circannual rhythm. Body weight rhythm persisted normally under warmer environmental conditions preventing the bats from hibernation. It is considered that the circannual cycles of fat gain and loss are relatively stable and not dependent on the hibernation cycle. Prolonged gestation period and delayed beginning of lactation by cold environment in summer did not affect the body weight rhythm. Temperature may be a more important environmental stimulus (or Zeitgeber) for the circannual rhythm than light and its effects may vary with phases.     

Kinematic changes using weightlifting shoes on barbell back squat

The purpose of this study was to validate a higher degree of foot segment angle by wearing the weightlifting (WL) shoes and to determine the kinematic differences between WL shoes and running shoes during the barbell back squat. College-aged individuals volunteered to participate in this study (N = 25). After warm-up, subjects performed 60% of 1RM barbell back squat. Reflective markers were placed on lower extremity joints and end of the bar to create segments to analyze kinematics of the barbell back squat from a 2-dimensional view. Three separate repeated measure analyses of variance were used at p = 0.05. Results showed that there was a difference between the footwear conditions; foot segment angle of 3.5° (p < 0.05) and trunk lean of 22 mm (p < 0.05) were captured when wearing WL shoes. However, thigh segment peak flexion angle was not statistically different (p = 0.37). Wearing WL shoes seems to be beneficial in reducing the overall trunk lean, because this position is believed to reduce the amount of shear stress in the lower back area. Back squat with WL shoes also increased foot segment angle and possibly contributes to greater muscle excitation in knee extensors. Weightlifting shoes did not help reach thigh segment closer to horizontal as compared with the running shoe condition. It is recommended that WL shoes be used by those who are prone to displaying a forward trunk lean and who aim to increase knee extensor activation.     

Site of allergic airway narrowing and the influence of exogenous surfactant in the Brown Norway rat

Background

The parameters R_N (Newtonian resistance), G (tissue damping), and H (tissue elastance) of the constant phase model of respiratory mechanics provide information concerning the site of altered mechanical properties of the lung. The aims of this study were to compare the site of allergic airway narrowing implied from respiratory mechanics to a direct assessment by morphometry and to evaluate the effects of exogenous surfactant administration on the site and magnitude of airway narrowing.

Methods

We induced airway narrowing by ovalbumin sensitization and challenge and we tested the effects of a natural surfactant lacking surfactant proteins A and D (Infasurf®) on airway responses. Sensitized, mechanically ventilated Brown Norway rats underwent an aerosol challenge with 5% ovalbumin or vehicle. Other animals received nebulized surfactant prior to challenge. Three or 20 minutes after ovalbumin challenge, airway luminal areas were assessed on snap-frozen lungs by morphometry.

Results

At 3 minutes, R_N and G detected large airway narrowing whereas at 20 minutes G and H detected small airway narrowing. Surfactant inhibited R_N at the peak of the early allergic response and ovalbumin-induced increase in bronchoalveolar lavage fluid cysteinyl leukotrienes and amphiregulin but not IgE-induced mast cell activation in vitro.

Conclusion

Allergen challenge triggers the rapid onset of large airway narrowing, detected by R_N and G, and subsequent peripheral airway narrowing detected by G and H. Surfactant inhibits airway narrowing and reduces mast cell-derived mediators.     

The presence of LPS in OVA inhalations affects airway inflammation and AHR but not remodeling in a rodent model of asthma

Ovalbumin (OVA) is the most frequently used allergen in animal models of asthma. Lipopolysaccharide (LPS) contaminating commercial OVA may modulate the evoked airway inflammatory response to OVA. However, the effect of LPS in OVA on airway remodeling, especially airway smooth muscle (ASM) has not been evaluated. We hypothesized that LPS in commercial OVA may enhance allergen-induced airway inflammation and remodeling. Brown Norway rats were sensitized with OVA on day 0. PBS, OVA, or endotoxin-free OVA (Ef-OVA) was instilled intratracheally on days 14, 19, 24. Bronchoalveolar lavage (BAL) fluid, lung, and intrathoracic lymph node tissues were collected 48 h after the last challenge. Immunohistochemistry for α-smooth muscle actin, Periodic-Acid-Schiff staining, and real-time qPCR were performed. Airway hyperresponsiveness (AHR) was also measured. BAL fluid macrophages, eosinophils, neutrophils, and lymphocytes were increased in OVA-challenged animals, and macrophages and neutrophils were significantly lower in Ef-OVA-challenged animals. The ASM area in larger airways was significantly increased in both OVA and Ef-OVA compared with PBS-challenged animals. The mRNA expression of IFN-γ and IL-13 in lung tissues and IL-4 in lymph nodes was significantly increased by both OVA and Ef-OVA compared with PBS and were not significantly different between OVA and Ef-OVA. Monocyte chemoattractant protein (MCP)-1 in BAL fluid and AHR were significantly increased in OVA but not in Ef-OVA. LPS contamination in OVA contributes to the influx of macrophages and MCP-1 increase in the airways and to AHR after OVA challenges but does not affect OVA-induced Th1 and Th2 cytokine expression, goblet cell hyperplasia, and ASM remodeling.     

Influence of weight distribution asymmetry on the biomechanics of a barbell back squat

The purpose of this study was to investigate the influence of weight distribution (WtD) asymmetry on the biomechanics of a barbell back squat. This study included 2 groups of trained individuals who were separated based on a WtD test (n = 14 in each group). They performed the barbell back squats with 2 resistance levels (60 and 75% of 1 repetition maximum) to measure vertical ground reaction force (GRF), tilting, and rotational angular bar displacements. A symmetry index (SI) score of the vertical GRF and the 2 bar displacements were examined to identify the group difference. Results showed that the unequal WtD group displayed a higher vertical GRF SI score (p < 0.05) and greater degrees of the tilting (p < 0.05) and rotational (p < 0.05) angular bar displacements. The 2 resistances did not influence the magnitude of the dependent variables, and no interactions were found. The unequal WtD captured at the WtD test carried over to the SI score during the back squat test. The unequal WtD was also a partial factor of displaying greater bar displacements. The lack of postural control to distribute body weight evenly should be treated properly to gain levelness before participating in high volume of resistance training, and coaches should be conscious of moving in a symmetrical fashion with minimal bar displacements in tilting and rotational manner.     

New detection of a 30-year-old population of introduced mongoose <Emphasis Type="Italic">Herpestes auropunctatus</Emphasis> on Kyushu Island,Japan

The small Indian mongoose Herpestes auropunctatus, which was recently determined to be a separate species from the Javan mongoose H. javanicus, is one of the most notorious invasive predators known. A population of Herpestes sp. was recently reported at Kagoshima prefecture on Kyushu Island, one of the main Japanese islands. Surprisingly, the trapping actions and information from residents after this report suggest that this Herpestes sp. population has been established in this area for at least 30 years. In this study, based on mitochondrial DNA sequences, we identified seven recently obtained Herpestes sp. individuals from this area as H. auropunctatus, confirming that an additional mongoose population has been established on Kyushu Island. Confirmation of the spatial distribution of the mongoose and surveillance systems in surrounding areas are urgently needed to prevent further expansion of this mongoose’s distribution. It also highlights the large gap between the accepted scientific knowledge relating to biosecurity against biological invasion and local knowledge on the ground, even when the introduced species is notorious and relatively conspicuous. Recent progressions of invasibility studies would greatly contribute to the prioritization of allocating adequate resources to areas with high invasion risks.