Background: Particulate matter 10 (PM 10 ; airborne particles <10 μm) has been demonstrated to induce airway and lung diseases. We aimed to investigate the effects of PM 10 on RNA expression in lung using a murine model. Methods: Female BALB/c mice were treated with PM 10 , ovalbumin (OVA), or both (OVA/ PM 10). PM 10 was intranasally administered four times over 2 weeks, and OVA was intraperitoneally injected and then intranasally administered. After 2 days from the last challenges, mice were sacrificed. Full RNA sequencing using lung homogenates was conducted. Results: PM 10 did not induce cell proliferation in bronchoalveolar fluid, and it also did not lead to airway hyper-responsiveness, but it did cause airway inflammation and lung fibrosis. Levels of IL-1β, TNF-α, and TGF-β in lung homogenates were significantly higher in the PM 10-treated group, compared to the control group. The PM 10 model showed increased RNA expression of Rn45a, Snord22, Atp6v0c-ps2, Snora28, Snord15b, Snora70, and Mmp12. Generally, genes associated with RNA splicing, DNA repair, the inflammatory response, the immune response, cell death, and apoptotic processes were highly expressed in the PM 10treated group. OVA/PM 10 treatment did not produce greater effects than OVA alone. However, the OVA/PM 10-treated group did show increased RNA expression of Clca1, Snord22, Retnla, Prg2, Tff2, Atp6v0c-ps2, and Fcgbp compared to the control group. These genes are associated with RNA splicing, DNA repair, the inflammatory response, and the immune response. Conclusions: Inhalation of PM 10 changed RNA expression in extensive range, and it also induced increase inflammatory cytokines, cellular inflammation, and fibrosis, in murine model.

Jung-Won park 2,3 & Jae-Hyun Lee 2,3* CD93 has been shown critical roles in inflammatory and immune diseases. However, in allergic asthma, the potential roles of soluble CD93 (sCD93) have not been well studied. We conducted house dust mite (HDM) stimulation with Der p 1 in BEAS-2B and U937 cells, followed by treatment with dexamethasone or small interfering RNA against CD93. A HDM-induced murine allergic asthma model was also established. We estimated the power of sCD93 to predict allergic asthma in a retrospective post-hoc analysis containing 96 human samples. HDM-stimulated BEAS-2B cells showed increased mRNA expression levels of IL-6, IL-8, IL-33, TSLP, and CD93. The CD93 level in culture supernatants steadily increased for 24 h after allergen stimulation, which was significantly suppressed by both dexamethasone and CD93 silencing. CD93 silencing increased IL-6 and TSLP, but not IL-33 levels in culture supernatants. HDM-induced asthma mice showed significant airway hyperresponsiveness and inflammation with Th2 cytokine activation, along with decreased CD93 expression in bronchial epithelial cells and lung homogenates but increased serum CD93 levels. The sCD93 level in asthma patients was significantly higher than that in healthy controls and could predict asthma diagnosis with moderate sensitivity (71.4%) and specificity (82.4%) (AUC = 0.787, P < 0.001). The level of sCD93 which has potential role to predict asthma significantly increased after HDM stimulation via IL-6 and TSLP in vitro and in vivo. Asthma is a chronic inflammatory airway disease that is typically diagnosed based on a pulmonary function test with a bronchodilator and a bronchial provocation test 1. However, these tests require the effort and cooperation of the patient, which is often impossible owing to old age, deafness, misunderstanding, severe dyspnea, paroxysmal cough, and risk of an asthma attack 2. Therefore, there is a clinical need to identify a serum biomarker that can act as a non-invasive method of diagnosis for asthma patients; although several biomarkers have been suggested, they are not widely used in clinical settings owing to limited evidence 3,4. CD93 (C1qRp) is a transmembrane glycoprotein that is expressed on various cell types, including endothelial cells, epithelial cells, stem cells, platelets, and leukocytes 5,6. CD93 can be shed in a soluble form (sCD93) in response to inflammatory mediators, can be easily measured, and is considered to be associated with various inflammatory and immune associated diseases, including asthma 7,8. In addition, CD93 has angiogenic and growth-stimulating effects 9-11. Raedler et al. 12 showed that CD93 gene expression was significantly higher in non-allergic asthma patients than healthy controls, and Sigari et al. 13 demonstrated that the serum CD93 level increased under asthma exacerbation and decreased following proper treatment. We also previously reported the potential of sCD93 as a novel biomarker for asthma using an ovalbumin-induced asthma murine model and human patients 14,15. Howev...

Vanillin is a phenolic aldehyde, which is found in plant species of the Vanilla genus. Although recent studies have suggested that vanillin has various beneficial properties, the effect of vanillin on blood vessels has not been studied well. In the present study, we investigated whether vanillin has vascular effects in rat mesenteric resistance arteries. To examine the vascular effect of vanillin, we measured the isometric tension of arteries using a multi-wire myograph system. After the arteries were pre-contracted with high K+ (70 mM) or phenylephrine (5 µM), vanillin was administered. Vanillin induced concentration-dependent vasodilation. Endothelial denudation or treatment of eNOS inhibitor (L-NNA, 300 μM) did not affect the vasodilation induced by vanillin. Treatment of K+ channel inhibitor (TEA, 10 mM) or sGC inhibitor (ODQ, 10 μM) or COX-2 inhibitor (indomethacin, 10 μM) did not affect the vanillin-induced vasodilation either. The treatment of vanillin decreased the contractile responses induced by Ca2+ addition. Furthermore, vanillin significantly reduced vascular contraction induced by BAY K 8644 (30 nM). Vanillin induced concentration-dependent vascular relaxation in rat mesenteric resistance arteries, which was endothelium-independent. Inhibition of extracellular Ca2+ influx was involved in vanillin-induced vasodilation. Treatment of vanillin reduced phopsho-MLC20 in vascular smooth muscle cells. These results suggest the possibility of vanillin as a potent vasodilatory molecule.

RATIONALE: To control therapy-resistant eosinophilia, synergistic effects of CTLA4-Ig and glucocorticoid was investigated on T cellinduced asthma model. METHODS: Ovalbumin (OVA) specific murine helper T cell (Th) clones were established from splenocytes of DO11.10 transgenic mice expressing T cell receptor specific for OVA/H-2 d . To analyze steroid responsiveness in vitro, Th clones were cultured with antigen presenting cells and OVA in the presence of various concentration of dexamethasone (DEX). Proliferative responses were measured by incorporation of either 3 H-thymidine or BrdU. For in vivo analysis, unprimed Balb/c mice were transferred with Th clones, challenged with OVA, and administered with DEX subcutaneously. CTLA4-Ig was administered either intravenously or intranasally. Bronchoalveolar lavage fluid (BALF) was obtained 48 hours after the challenge, and the number of infiltrating cells was differentially counted. RESULTS: Steroid-sensitive (SS) and -resistant (SR) clones were selected based on the effect of DEX on the proliferative responses of antigenstimulated Th clones. Airway infiltration of eosinophils of mice transferred with SS clones were effectively inhibited by the administration of DEX. In contrast, those of mice transferred with SR clones were not significantly inhibited by DEX. Addition of CTLA4-Ig into the culture significantly suppressed the proliferation of DEX-treated SR clones in vitro. Administration of CTLA4-Ig significantly suppressed eosinophil infiltration of SR asthma model transferred with SR clones in vivo. CTLA4-Ig and DEX synergistically suppressed in vitro proliferation of SS clones and in vivo BALF eosinophilia of mice transferred with SS clones. CONCLUSIONS: Blocking costimulatory signal mediated through CD28 is a promising target to treat therapy-resistant eosinophilia.