Effects of Corticosteroids on Osteopontin Expression in a Murine Model of Allergic Asthma

Kurokawa, Masatsugu; Konno, Satoshi; Matsukura, Satoshi; Kawaguchi, Mio; Ieki, Koushi; Suzuki, Shintarou; Odaka, Miho; Watanabe, Shin; Homma, Tetsuya; Sato, Masayuki; Takeuchi, Hiroko; Hirose, Takashi; Huang, Shau Ku; Adachi, Mitsuru

doi:10.1159/000210647

Cited by 22 publications

(25 citation statements)

References 73 publications

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“…Although we found that valsartan treatment and a reduction of ln CRP levels were independent determinants of a reduction in OPN levels, it is difficult to conclude that an antiinflammatory effect of valsartan is necessary to reduce OPN levels. Kurakawa et al 24 reported that in a murine model of allergic asthma, increased OPN protein in the broncho-alveolar lavage was inhibited by the corticosteroids, anti-inflammatory drugs. Although their model is completely different in our study subject, anti-inflammatory drugs certainly reduce OPN expression.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II receptor blockade with valsartan decreases plasma osteopontin levels in patients with essential hypertension

et al. 2010

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Osteopontin (OPN) has recently emerged as a key factor in both vascular remodelling and development of atherosclerosis. It has been reported that OPN is regulated by the renin-angiotensin-aldosterone system (RAAS). The aim of this study was to clarify the effect of angiotensin II receptor blockade with valsartan on plasma OPN levels in patients with essential hypertension (EHT). Forty-six patients (mean age, 64 ± 11 years) with EHT were randomly assigned to treatment with amlodipine or valsartan. There were no significant differences in baseline clinical characteristics between the two groups. Blood sampling and blood pressure evaluation were performed before and after 24 weeks of treatment. After 24 weeks, both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were decreased significantly and by the same degree in each treatment group. However, valsartan but not amlodipine decreased plasma OPN levels (baseline and 24-week data-valsartan: 614±224 ng ml À1, 472±268 ng ml À1 , P ¼ 0.006; amlodipine: 680 ± 151 ng ml À1 , 687 ± 234 ng ml À1 , P40.999). A positive correlation between the reduction in OPN and the log natural (ln) C-reactive protein (CRP) was seen in the valsartan-treated group. Stepwise regression analysis showed that treatment with valsartan and the reduction of ln CRP were associated with the reduction in OPN levels, and this association was independent of the reduction in SBP or aldosterone levels (valsartan: b ¼ 0.332, P ¼ 0.026; ln CRP reduction: b ¼ 0.366, P ¼ 0.015). These results suggest that suppression of the RAAS and inflammation may decrease plasma OPN levels.

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Section: Discussionmentioning

confidence: 99%

Angiotensin II receptor blockade with valsartan decreases plasma osteopontin levels in patients with essential hypertension

et al. 2010

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“…Furthermore, no differences were found in serum OPN levels before and after 2 weeks of oral steroid treatment. In a recent study using a murine model of asthma, dexamethasone was found to decrease BALF OPN levels and lung tissue mRNA expression [34]. However, the amount of steroids used in this study (3 mg?kg -1 dexamethasone or 20 mg?kg -1 prednisolone) is ,200 times greater than the dose of oral prednisolone used in the present study, and 40 times higher than what current guidelines suggest for the management of severe exacerbations of asthma [16].…”

Section: ) T-lymphocytes (Fig 4q-t) and Mast Cells (mentioning

confidence: 95%

Osteopontin expression and relation to disease severity in human asthma

Samitas¹,

Ζervas²,

Vittorakis³

et al. 2010

European Respiratory Journal

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Recent studies have associated osteopontin (OPN) with allergic inflammation; however, its role in human asthma remains unclear. The aim of this study was to measure OPN levels in the serum, bronchoalveolar lavage fluid (BALF) and bronchial tissue of healthy controls and asthmatics, identify cellular sources of OPN and examine possible correlations between OPN expression, disease severity and airway remodelling.Serum samples were obtained from 35 mild-to-moderate asthmatics, 19 severe asthmatics and 17 healthy controls in the steady state and in cases of exacerbation. Of these subjects, 29 asthmatics and nine controls underwent bronchoscopy with endobronchial biopsy and BALF collection. OPN expression was determined by ELISA and immunohistochemistry/immunofluorescence. Reticular basement membrane thickness and goblet cell hyperplasia were also determined.Serum and BALF OPN levels were significantly increased in all asthmatics in the steady state, whereas serum levels decreased during exacerbations. OPN was upregulated in the bronchial tissue of all patients, and expressed by epithelial, airway and vascular smooth muscle cells, myofibroblasts, T-lymphocytes and mast cells. OPN expression correlated with reticular basement membrane thickness and was more prominent in subepithelial inflammatory cells in severe compared to mild-to-moderate asthma.OPN expression is upregulated in human asthma and associated with remodelling changes, and its subepithelial expression correlates with disease severity.

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“…The protocol for antigen sensitization and challenge has been described previously [24,25]. Mice were actively sensitized by intraperitoneal injection of 50 µg ovalbumin (OVA; grade V; Sigma, Tokyo, Japan) with 1 mg alum (Sigma) on days 0, 7, 14, and 21 of the experiment.…”

Section: Animals and Methodsmentioning

confidence: 99%

Expression and Effects of IL-33 and ST2 in Allergic Bronchial Asthma: IL-33 Induces Eotaxin Production in Lung Fibroblasts

Kurokawa

Matsukura

Kawaguchi

et al. 2011

Int Arch Allergy Immunol

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Background: Interleukin (IL)-33, a new member of the IL-1 cytokine family, has been recognized as a key cytokine that enhances T helper 2-balanced immune regulation through its receptor ST2; however, the function and relationship of the IL-33 and ST2 pathways in bronchial asthma are still unclear. We investigated the cellular origin and regulation of IL-33 and ST2 in allergic bronchial asthma in vivo and in vitro. Methods: BALB/c mice were sensitized by intraperitoneal injections of ovalbumin (OVA) with alum. Mice were exposed to aerosolized 1% OVA for 30 min a day for 7 days. These mice were then challenged with aerosolized 1% OVA 2 days after the last day of exposure. After the OVA challenge, the mice were sacrificed and their lung tissues were obtained. Mouse lung fibroblasts were cultured and treated with IL-33 or IL-13. Results: The levels of IL-33 mRNA and IL-33 protein in lung tissue increased after the OVA challenge. Most IL-33-expressing cells were CD11c+ cells and epithelial cells, and many ST2-expressing cells were stained lung fibroblasts and inflammatory cells. IL-33 induced eotaxin/CCL11 production in lung fibroblasts. IL-33 and IL-13 synergistically induced eotaxin expression. Conclusions: IL-33 may contribute to the induction and maintenance of eosinophilic inflammation in the airways by acting on lung fibroblasts. IL-33 and ST2 may play important roles in allergic bronchial asthma.

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Effects of Corticosteroids on Osteopontin Expression in a Murine Model of Allergic Asthma

Cited by 22 publications

References 73 publications

Angiotensin II receptor blockade with valsartan decreases plasma osteopontin levels in patients with essential hypertension

Angiotensin II receptor blockade with valsartan decreases plasma osteopontin levels in patients with essential hypertension

Osteopontin expression and relation to disease severity in human asthma

Expression and Effects of IL-33 and ST2 in Allergic Bronchial Asthma: IL-33 Induces Eotaxin Production in Lung Fibroblasts

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