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Nebulized lidocaine has been suggested to be beneficial in asthma therapy, but the underlying mechanisms are little known. We aimed to investigate whether Toll-like receptor (TLR) 2 was involved in the protective effect of lidocaine on allergic airway inflammation. Female C57BL/6 mice were sensitized and challenged with ovalbumin (OVA). Meanwhile, some of the mice were treated with TLR2 agonist (Pam3CSK4, 100 μg) intraperitoneally in combination with OVA on day 0. Just after allergen provocation, mice were treated with inhaled lidocaine or vehicle for 30 min. In this model, we found that lidocaine markedly attenuated OVA-evoked airway inflammation, leukocyte recruitment and mucus production. Moreover, lidocaine abrogated the increased concentrations of T cytokines and TNF-α in bronchoalveolar lavage fluid (BALF) of allergic mice, as well as reducing the expression of phosphorylated nuclear factor (P-NF)-κBp65 and the NOD-like receptor pyridine containing 3 (NLRP3), which are important for the production of pro-inflammatory cytokines. In addition, our study showed that lidocaine dramatically decreased OVA-induced increased expression of TLR2 in the lung tissues. Furthermore, activation of TLR2 aggravated OVA-challenged airway inflammation, meanwhile, it also elevated OVA-induced expression of P-NF-κBp65 and NLRP3 in the lungs. However, lidocaine effectively inhibited airway inflammation and counteracted the expression of P-NF-κBp65 and NLRP3 in allergic mice pretreated with Pam3CSK4. Taken together, the present study demonstrated that lidocaine prevented allergic airway inflammation via TLR2 in an OVA-induced murine allergic airway inflammation model. TLR2/NF-κB/NLRP3 pathway may serve as a promising therapeutic strategy for allergic airway inflammation. [ABSTRACT FROM AUTHOR]

Aims Glucocorticoids are the most effective anti-inflammatory agent in treating pulmonary diseases typically accompanied by hypoxia. Our previous study has demonstrated that glucocorticoid receptor α (GRα) expression is reduced in hypoxia but the underlying mechanism remains elusive. In this study we aim to identify the signaling pathway involved in hypoxia-induced down-regulation of GRα, and whether hypoxia affects nuclear translocation of GRα. Main methods Female C57BL/6 mice were sensitized with saline or ovalbumin (OVA) as the in vivo model. Mice were divided into control and OVA groups, and their lung histology and the expression of hypoxia inducible factor (HIF-1) and GRα were examined. A549 cells were exposed to chemical hypoxia as the in vitro model, where mitogen-activated protein kinases (MAPKs) were inhibited specifically by SB203580. Next, under normal or hypoxic conditions, the expression of GRα, MAPKs and HIF-1 signal protein were determined by Western blot analysis, and GRα translocation were observed through live-cell imaging. Key findings In OVA challenged mice the expression of GRα was down-regulated whereas HIF-1 was up-regulated. Hypoxia caused a time-dependent decrease of GRα expression, and activated multiple signaling pathways including MAPKs and HIF-1. Moreover, GRα expression increased with MAPK inhibition. Interestingly, only MAPK inhibitor SB203580, but not JNK inhibitor SP600125 or ERK inhibitor U0126 improved the expression of GRα under hypoxic condition. GRα nuclear translocation was also significantly inhibited by hypoxia. Significance Hypoxia down-regulated the expression of GRα through p38 signaling pathway, as well as inhibited GRα nuclear translocation significantly. [ABSTRACT FROM AUTHOR]

• A glucan (18.3 kDa) from purple sweet potato is composed of →4)Glc p (1→ glycosyls. • It branches at O -2, O -3, and O -6 positions with α- d -Glc p (1→ residue as side chain. • Its particle size is concentrated at 230 nm and has no triple-helix conformation. • Its height and width rangs from 1.0 to 6.1 nm and 65 to 210 nm, respectively. • Its maximum ring diameter and chain length is ∼800 nm and ∼7.0 μm, respectively. A novel glucan PSPP-1 (18.3 kDa) was purified from the foot tuber of purple sweet potato Ipomoea Batatas (L.) Lam. Its backbone was composed of →4)-α- d -Glc p (1→ glycosyl, and branching at the O -2, O -3, and O -6 positions with α- d -Glc p (1→ residues. X-ray diffraction experiment showed that PSPP-1 existed as an amorphous form. Its microstructure was detected via scanning electron microscopy. Its particle size was mainly concentrated at 230 nm in water. Congo red and circular dichroism experiments showed there was no triple-helix conformation. Atomic force microscopy data suggested that its height and width ranged from 1.0 to 6.1 nm and 65 to 210 nm, respectively; its maximum ring diameter and chain length was ∼800 nm and ∼7.0 μm, respectively. Furthermore, it exhibited inhibitory activities on HepG2, LOVO, and MCF-7 cells. Collectively, our data are useful for understanding the structural characteristics of sweet potato polysaccharides, and their application in foods and pharmaceutical areas. [ABSTRACT FROM AUTHOR]

Numerous studies indicate that toll-like receptor 2 (TLR2) led to divergent effects in asthma. The occurrence of autophagy in asthma pathogenesis is still incompletely understood. Here, we aimed to investigate the role of TLR2 and the underlying mechanisms in allergic airway inflammation and autophagy activation. C57BL/6 and TLR2 knockout (TLR2−/−) mice were subjected to an ovalbumin (OVA)-immunized allergic airway model, and were treated with SP600125. Differential cell counts in bronchoalveolar lavage fluid were determined by Wright's staining. Histological analysis of airway inflammation was determined by haematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining. The levels of OVA-specific immunoglobulin E (IgE), tumor necrosis factor α (TNF-α) and interleukin 10 (IL-10) were detected by enzyme-linked immunosorbent assay (ELISA). Proteins expression in lung tissues was detected by western blot, expression of TLR2 was further observed by immunofluorescence. Autophagy activation was determined by western blot and transmission electron microscopy (TEM). TLR2 expression was increased upon OVA challenge, and TLR2 deficiency was associated with decreased allergic airway inflammation. Meanwhile, TLR2 deficiency weakened autophagy activation. Moreover, inhibition of c-Jun N-terminal kinase (JNK) by SP600125 also suppressed OVA-induced allergic airway inflammation and autophagy activation. Interestingly, treating TLR2−/− mice with SP600125 showed similar OVA-induced allergic airway inflammation and autophagy activation compared to that in vehicle-treated TLR2−/− mice. TLR2 might contribute to the maintenance of allergic airway inflammation through JNK signaling pathway accompanying with autophagy activation. These findings may provide a novel signal target for prevention of allergic airway inflammation. [ABSTRACT FROM AUTHOR]