Role of the TSLP-DC-OX40L pathway in asthma pathogenesis and airway inflammation in mice.

This study aimed to explore the effect of the TSLP-DC-OX40L pathway in asthma pathogenesis and airway inflammation in mice. For this, 65 male BALF/c mice were distributed among the control, asthma, immunoglobulin G (IgG) + asthma (IgG, 500 µg/500 µL, intratracheal injection of 50 µL each time), LY294002 (OX40L inhibitor) + asthma (intratracheal injection of 2 mg/kg LY294002), and anti-TSLP + asthma (intratracheal injection of 500 µg/500 µL TSLP antibody, 50 µL each time) groups. ELISA was applied to measure the serum levels of immunoglobulin E (IgE), ovalbumin (OVA)-sIgE, interleukin-4 (IL-4), IL-5, IL-13, and interferon-γ (IFN-γ); flow cytometry was employed to detect Treg cells and dendritic cell (DC) and lymphopoiesis. RT-qPCR and Western blot assays were used to measure the levels of TSLP, OX40L, T-bet, GATA-3, NF-κB, p38, and ERK. Treatment with LY294002 and anti-TSLP resulted in increases in the numbers of total cells, eosinophils, neutrophils, and lymphocytes in the bronchoalveolar lavage fluid; total serum levels of IgE, OVA-sIgE, IL-4, IL-5, and IL-13; levels of DC cells; lymphopoiesis; and levels of TSLP, OX40L, GATA-3, NF-κB, p38, and ERK, whereas there were decreases in the levels of IFN-γ and CD4+CD25+Treg cells; CD4+Foxp3+Treg cells; and T-bet. The TSLP-DC-OX40L pathway may contribute to asthma pathogenesis and airway inflammation by modulating the levels of CD4+CD25+Treg cells and inflammatory cytokines.

[Role of transient receptor potential vanilloid 1 in airway inflammation in asthmatic mice].

OBJECTIVE: To study the effects of the change in transient receptor potential vanilloid 1 (TRPV1) channel activity on the degree of airway inflammation in asthmatic mice. METHODS: BALB/c mice were randomly divided into control, asthma, capsaicin (TRPV1 agonist), capsazepine (TRPV1 antagonist), and dexamethasone groups. The asthmatic mouse model was established by intraperitoneal injection of mixed ovalbumin-aluminium hydroxide solution and ultrasonic atomization with OVA for sensitization and challenge. The capsaicin, capsazepine, and dexamethasone groups were given intraperitoneal injection of capsaicin (30 µg/kg), capsazepine (10 µmol/kg), and dexamethasone (2 mg/kg) respectively, at 30 minutes before challenge. Hematoxylin and eosin staining was used to observe the degree of pulmonary inflammation. ELISA was used to measure the content of interleukin-8 (IL-8) and interleukin-13 (IL-13) in bronchoalveolar lavage fluid (BALF). Real-Time PCR was used to measure the relative content of TRPV1 mRNA in lung tissue. RESULTS: Compared with the asthma group, the capsazepine and dexamethasone groups showed reduced pulmonary inflammation, while the capsaicin group showed aggravated pulmonary inflammation. Compared with the control group, the asthma and capsaicin groups showed increases in the content of IL-13 and IL-8 in BALF and the mRNA expression of TRPV1 in lung tissue (P<0.05). Compared with the asthma group, the capsazepine and dexamethasone groups showed reductions in the content of IL-13 and IL-8 in BALF and the mRNA expression of TRPV1 in lung tissue (P<0.05). The capsaicin group showed increases in the content of IL-13 and IL-8 in BALF (P<0.05). CONCLUSIONS: TRPV1 channel agonist and antagonist can influence the degree of airway inflammation in asthmatic mice. Dexamethasone may reduce airway inflammation through regulating TRPV1 level.

[Investigation and OCRL mutation analysis of a family with oculocerebrorenal syndrome of Lowe].

Oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked recessive disorder. This study investigated the history of a Chinese family with OCRL and used direct DNA sequencing to screen all exons of OCRL gene for mutations. A missense mutation (1736 A→G) in exon 15 was revealed, which resulted in the change of His (H) 507 to Arg (R). The patient's mother was the carrier of the heterozygous mutation in X-chromosome. To our knowledge, H507R mutation in OCRL gene has not been reported in Chinese people.