Prior studies have reported the presence of lung fibrosis and enhanced airway hyperresponsiveness (AHR) in mice with high-fat-diet (HFD)-induced obesity. This study evaluated the role of TGF-β1 in HFD-induced AHR and lung fibrosis in a murine model. We generated HFD-induced obesity mice and performed glucose and insulin tolerance tests. HFD mice with or without ovalbumin sensitization and challenge were also treated with an anti-TGF-β1 neutralizing antibody. AHR to methacholine, inflammatory cells in the bronchoalveolar lavage fluid (BALF), and histological features were evaluated. Insulin was intranasally administered to normal diet (ND) mice, and in vitro insulin stimulation of BEAS-2b cells was performed. HFD-induced obesity mice had increased insulin resistance, enhanced AHR, peribronchial and perivascular fibrosis, and increased numbers of macrophages in the BALF. However, they did not have meaningful eosinophilic or neutrophilic inflammation in the lungs compared with ND mice. The HFD enhanced TGF-β1 expression in the bronchial epithelium, but we found no differences in the expression of interleukin (IL)−4 or IL-5 in lung homogenates. Administration of the anti-TGF-β1 antibody attenuated HFD-induced AHR and lung fibrosis. It also attenuated goblet cell hyperplasia, but did not affect the AHR and inflammatory cell infiltration induced by OVA challenge. The intranasal administration of insulin enhanced TGF-β1 expression in the bronchial epithelium and lung fibrosis. Stimulating BEAS-2b cells with insulin also increased TGF-β1 production by 24 h. We concluded that HFD-induced obesity-associated insulin resistance enhances TGF-β1 expression in the bronchial epithelium, which may play an important role in the development of lung fibrosis and AHR in obesity.

BackgroundSilica nanoparticles (SNPs) can easily enter in respiratory system via inhalation because of their low molecular weight and ease of dispersion. Toxicity and adverse effects of SNPs vary according to the physical characteristics of the particle.MethodsTo evaluate the toxic and adjuvant effects of 3 types of SNPs in the airway system, six-week-old female BALB/c mice were intranasally administered 3 types of SNPs (spherical [S-SNP], mesoporous [M-SNP], and polyethylene glycol-conjugated [P-SNP]) alone or SNPs/ovalbumin (OVA), three times weekly for 2 weeks. Airway hyper-responsiveness (AHR), bronchoalveolar lavage fluid (BALF), cytokine levels, and histology of the lungs were analyzed.ResultsThe S-SNPs/OVA group and M-SNPs/OVA group showed significant AHR, compared to the control group. Among all SNP-treated groups, the group administered SNPs/OVA showed greater inflammatory cell infiltration in BALF, extensive pathological changes, and higher cytokine levels (IL-5, IL-13, IL-1β, and IFN-γ) than those administered SNPs alone or saline/OVA.ConclusionExposure to SNPs alone and SNPs/OVA induced toxicity in the respiratory system. SNPs alone showed significant toxic effects on the airway system. Meanwhile, SNPs/OVA exerted adjuvant effects to OVA of inducing allergic airway inflammation. In particular, M-SNPs showed the most severe airway inflammation in both direct toxicity and adjuvant effect assays. P-SNPs induced less inflammation than the other types of SNPs in both models.

Obese patients with asthma respond poorly to conventional asthma medications, resulting in severe symptoms and poor prognosis. Roflumilast, a phosphodiesterase-4 inhibitor that lowers the levels of various substances that are implicated in obese subjects with asthma, may be effective in the treatment of those subjects. We evaluated the potential of roflumilast as a novel therapeutic agent for obese subjects with asthma. We designed three models: diet-induced obesity (DIO); DIO with ovalbumin (OVA); and OVA. We fed C57BL/6J mice a high-fat diet for 3 months with or without OVA sensitization and challenge. Roflumilast or dexamethasone was administered orally three times at 2-day intervals in the last experimental week. Airway hyperresponsiveness resulting from DIO significantly improved in the roflumilast-treated group compared with the dexamethasone-treated groups. Although DIO did not affect the cell proliferation in bronchoalveolar lavage fluid, increased fibrosis was seen in the DIO group, which significantly improved from treatment with roflumilast. DIO-induced changes in adiponectin and leptin levels were improved by roflumilast, whereas dexamethasone aggravated them. mRNA levels and proteins of TNF-α, transforming growth factor-β, IL-1β, and IFN-γ increased in the DIO group and decreased with roflumilast. The reactive oxygen species levels were also increased in the DIO group and decreased by roflumilast. In the DIO plus OVA and OVA models, roflumilast improved Th1 and Th2 cell activation to a greater extent than dexamethasone. Roflumilast is significantly more effective than dexamethasone against airway hyperresponsiveness caused by DIO in the murine model. Roflumilast may represent a promising therapeutic agent for the treatment of obese patients with asthma.

PurposeCD93 is receiving renewed attention as a biomarker of inflammation. We aimed to evaluate the potential for serum sCD93 to serve as a novel biomarker for allergic inflammation.Materials and MethodsWe enrolled 348 subjects with an allergic disease [allergic rhinitis (AR), chronic spontaneous urticaria (CSU), or bronchial asthma (BA)], including 14 steroid-naïve BA patients who were serially followed-up.ResultsThe serum sCD93 levels (ng/mL) in patients with exacerbated AR (mean±standard deviation, 153.1±58.4) were significantly higher than in patients without AR (132.2±49.0) or with stable AR (122.3±42.1). Serum sCD93 levels in exacerbated CSU (169.5±42.8) were also significantly higher than those in non-CSU (132.4±51.6) and stable CSU (122.8±36.2). This trend was also seen in BA. Serum levels in patients with ICS-naïve BA (161.4±53.1) were significantly higher than those in healthy controls without BA (112.2±30.8), low- and medium-dose ICS users. Serum sCD93 levels in high-dose ICS users (72.2±20.6) were significantly lower than those in low- and medium-dose users. The serum sCD93 levels in steroid-naïve patients with BA (195.1±72.7) decreased after ICS use for 4 weeks (134.4±42.8) and 8 weeks (100.7±13.4), serially.ConclusionElevated serum sCD93 levels reflected exacerbated status of allergic diseases, including CSU, AR, and asthma. ICS use significantly diminished serum sCD93 levels in steroid-naïve patients with BA. This result may suggest sCD93 in serum as a therapeutic marker for allergic inflammation.

Our findings demonstrate the potential of using sCD93 as a biomarker for allergic asthma.

Table of ContentsA1 Pirfenidone inhibits TGF-b1-induced extracellular matrix production in nasal polyp-derived fibroblastsJae-Min Shin, Heung-Man Lee, Il-Ho ParkA2 The efficacy of a 2-week course of oral steroid in the treatment of chronic spontaneous urticaria refractory to antihistaminesHyun-Sun Yoon, Gyeong Yul ParkA3 The altered distribution of follicular t helper cells may predict a more pronounced clinical course of primary sjögren’s syndromeMargit ZeherA4 Betamethasone suppresses Th2 cell development induced by langerhans cell like dendritic cellsKatsuhiko Matsui, Saki Tamai, Reiko IkedaA5 An evaluation of variousallergens in cases of allergic bronchial asthma at lucknow and neighbouring districts by intradermal skintestDrsushil Suri, Dranu SuriA6 Evaluation ferqency of ADHD in childhood asthmaMarzieh Heidarzadeh AraniA7 Steven johnson syndrome caused by typhoid fever in a childAzwin Lubis, Anang EndaryantoA8 Chronic Bronchitis with Radio Contrast Media Hypersensitivity: A Case with Hypothesized GINA Step 1 AsthmaShinichiro KogaA9 The association between asthma and depression in Korean adult : An analysis of the fifth korea national health and nutrition examination survey (2010-2012)Lee Ju SukA10 Management of allergic disease exacerbations in pregnancyYasunobu TsuzukiA11 Subcutaneous immunotherapy mouse model for atopic dermatitisSeo Hyeong Kim, Jung U Shin, Ji Yeon Noh, Shan Jin, Shan Jin, Hemin Lee, Jungsoo Lee, Chang Ook Park, Kwang Hoon Lee, Kwang Hoon LeeA12 Atopic disease and/or atopy are risk factors for local anesthetic allergy in patients with history of hypersensitivity reactions to drugs?Fatma Merve TepetamA13 Food hypersensitivity in patients with atopic dermatitis in KoreaChun Wook Park, Jee Hee Son, Soo Ick Cho, Yong Se Cho, Yun Sun Byun, Yoon Seok Yang, Bo Young Chung, Hye One Kim, Hee Jin ChoA14 Anaphylaxis caused by an ant (Brachyponera chinensis) in JapanYoshinori Katada, Toshio Tanaka, Akihiko Nakabayashi, Koji Nishida, Kenichi Aoyagi, Yuki Tsukamoto, Kazushi Konma, Motoo Matsuura, Jung-Won Park, Yoshinori Harada, Kyoung Yong Jeong, Akiko Yura, Maiko YoshimuraA15 Anti-allergic effect of anti-IL-33 by suppression of immunoglobulin light chain and inducible nitric oxide synthaseTae-Suk Kyung, Young Hyo Kim, Chang-Shin Park, Tae Young Jang, Min-Jeong Heo, Ah-Yeoun Jung, Seung-Chan YangA16 Food hypersensitivity in patients with chronic urticaria in KoreaHye One Kim, Yong Se Cho, Yun Sun Byun, Yoon Seok Yang, Bo Young Chung, Jee Hee Son, Chun Wook Park, Hee Jin ChoA17 Dose optimizing study of a depigmented polymerized allergen extract of phleum pollen by means of conjunctival provocation test (CPT)Angelika Sager, Oliver PfaarA18 Correlation of cutaneous sensitivity and cytokine response in children with asthmaAmit Agarwal, Meenu Singh, Bishnupda Chatterjee, Anil ChauhanA19 Colabomycin E, a Streptomycete-Derived Secondary Metabolite, Inhibits Proinflammatory Cytokines in Human Monocytes/MacrophagesIlja Striz, Eva Cecrdlova, Katerina Petrickova, Libor Kolesar, Alena Sekerkova, Veronika Svachov...

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