BACKGROUND AND PURPOSETransglutaminase 2 (TGase 2) expression is increased in inflammatory diseases, and TGase 2 inhibitors block these increases. We examined whether the R2 peptide inhibited the expression of TGase 2 in a mouse model of inflammatory allergic asthma. EXPERIMENTAL APPROACHC57BL/6 mice were sensitized and challenged by ovalbumin (OVA) to induce asthma. OVA-specific serum IgE and leukotrienes (LTs) levels were measured by enzyme-linked immunosorbent assay. Recruitment of inflammatory cells into bronchoalveolar lavage (BAL) fluid or lung tissues and goblet cell hyperplasia were assessed histologically. Airway hyperresponsiveness was determined in a barometric plethysmographic chamber. Expression of TGase 2, eosinophil major basic protein (EMBP), the adhesion molecule vascular cell adhesion molecule-1, Muc5ac and phospholipase A2 (PLA2) protein were determined by Western blot. Expression of mRNAs of Muc5ac, cytokines, matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) were measured by reverse transcriptase-polymerase chain reaction and nuclear factor-kB (NF-kB) by electrophoretic mobility shift assay. KEY RESULTSR2 peptide reduced OVA-specific IgE levels; the number of total inflammatory cells, macrophages, neutrophils, lymphocytes and eosinophils in BAL fluid and the number of goblet cells. Airway hyperresponsiveness, TGase 2 and EMBP levels, mRNA levels of interleukin (IL)-4, IL-5, IL-6, IL-8, IL-13, RANTES, tumour necrosis factor-a, and MMP2/9, Muc5ac, NF-kB activity, PLA2 activity and expressions, and LT levels in BAL cells and lung tissues were all reduced by R2 peptide. R2 peptide also restored expression of TIMP1/2. CONCLUSION AND IMPLICATIONSR2 peptide reduced allergic responses by regulating NF-kB/TGase 2 activity in a mouse model of allergic asthma. This peptide may be useful in the treatment of allergic asthma. AbbreviationsBAL, bronchoalveolar lavage; ELISA, enzyme-linked immunosorbent assay; EMBP, eosinophil major basic protein; EMSA, electrophoretic mobility shift assay; MMP, matrix metalloproteinase; NF-kB, nuclear factor-kappa B; OVA, ovalbumin; PAS, periodic acid-Schiff; PBS, phosphate buffered saline; PLA2, phospholipase A2; RT-PCR, reverse transcriptase-polymerase chain reaction; TGase 2, transglutaminase 2; TIMP, tissue inhibitor of matrix metalloproteinase BJP British Journal of Pharmacology
Effective sustainable algal cultivation techniques are essential for mass production of the marine microalga Tetraselmis for biofuel and array of co-products. The phycospheric communities affect the microalgal growth and metabolism through various allelochemical and nutrient interactions; hence, their potential to affect the quantity and quality of both biomass and bioproducts is significant. In the present study, we have screened the phycospheric communities of biofuel producing Tetraselmis striata (KCTC1432BP). A total of 26 bacterial strains were isolated and identified from the phycosphere of T. striata mass culture. Then, each bacterial strain was tested in co-cultivation conditions with T. striata for evaluating its growth promoting and inhibitory effects. Among these all strains, two promising strains (Pelagibaca bermudensis KCTC 13073BP and Stappia sp. KCTC 13072BP) were selected because of their maximum growth promoting effects and mutualistic interactions. The growth rate, biomass productivity, lipid contents, and fatty acids were analyzed during their combined growth in O3 media and compared with axenic growth of T. striata. Later, growth promoting mechanisms in the co-cultivation environment were investigated for these promising bacterial strains under replete and limited conditions of nutrients (nitrate, phosphate, and vitamin B12). The growth promoting potential of P. bermudensis was illustrated by the two fold enhancement in biomass productivity. These bacteria are promising for microalgal cultivation without any negative effects on the native seawater bacterial communities, as revealed by next generation sequencing analysis. This study represents, to date, the first report highlighting the role of phycospheric growth promoting bacteria of promising biofuel feedstock T. striata.
Gamma radiation is used for several therapeutic indications such as cancers and autoimmune diseases. Low-dose whole-body γ irradiation has been shown to activate immune responses in several ways, however, the effect and mechanism of irradiation on allergic asthma remains poorly understood. This study investigated whether or not irradiation exacerbates allergic asthma responses and its potential mechanism. C57BL/6 mice were sensitized and challenged with ovalbumin (OVA) to induce asthma. The mice received whole-body irradiation once daily for 3 consecutive days with a dose of 0.667 Gy using (137)Cs γ rays 24 h before every OVA challenge. Repeated low-dose irradiation reduced OVA-specific IgE levels, the number of inflammatory cells including mast cells, goblet cell hyperplasia, collagen deposition, airway hyperresponsiveness, expression of inflammatory cytokines, CCL2/CCR2, as well as nuclear factor kappa B (NF-κB) and activator protein-1 activities. All of these factors were increased in BAL cells and lung tissue of OVA-challenged mice. Irradiation increased the number of Treg cells, expression of interleukin (IL)-10, IL-2 and IL-35 in BAL cells and lung tissue. Irradiation also increased Treg cell-expressed Foxp3 and IL-10 by NF-κB and RUNX1 in OVA-challenged mice. Furthermore, while Treg cell-expressing OX40 and IL-10 were enhanced in lung tissue or act-bone marrow-derived mast cells (BMMCs) with Treg cells, but BMMCs-expressing OX40L and TGF-β were decreased. The data suggest that irradiation enhances Foxp3(+)- and IL-10-producing Treg cells, which reduce OVA-induced allergic airway inflammation and tissue remodeling through the down-regulation of migration by the CCL2/CCR2 axis and activation of mast cells via OX40/OX40L in lung tissue of OVA-challenged mice.
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