Stephanie Shore

..Understanding the mechanistic basis for the interactions between these cytokines and airway smooth muscle might suggest new avenues for therapeutic intervention in asthma...

..3. Understanding the mechanistic basis for the effects of these cytokines may prove to be an important step in improving the efficacy of beta-adrenoceptor agonists for the treatment of asthma...

..Epidemiologic data indicate an increased incidence of asthma in the obese...

..Understanding the mechanistic basis for the relationship between obesity and asthma could lead to new therapeutic strategies for treatment of this susceptible population...

..Understanding the mechanistic basis for the relationship between obesity and asthma may lead to new therapeutic strategies for treatment of this susceptible population...

..Epidemiologic data indicate that the incidence of asthma is increased in obese patients...

..Our results also indicate that the hormone leptin, which is increased in the obese, has the capacity to increase airway inflammation...

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..A new study describes one possible mechanism and reveals a potential new therapeutic target in the treatment of asthma...

..Understanding the regulation of beta-adrenergic responses in airway smooth muscle cells may prove to be an important step in improving the efficacy of beta-agonists for the treatment of asthma...

..Understanding the mechanistic basis for the relationship between obesity and asthma may lead to novel therapeutic strategies for treatment of the obese asthmatic subject...

..The results suggest that immature mice are less sensitive than adult mice to O(3), at least in terms of the ability of O(3) to induce airway hyperresponsiveness and promote release of certain cytokines...

..The results indicate that the ventilatory response to O(3) is absent in 2-wk-old rats and that lack of this response, in conjunction with a greater specific ventilation, leads to greater lung injury...

..In summary, the neutrophilic inflammation induced by prolonged low level ozone exposure was attenuated in obese mice and appeared to result from an absence of IL-6-dependent neutrophil recruitment in the obese mice...

..Determining how obesity promotes asthma may uncover novel therapeutic strategies that are effective in the obese asthmatic subject...

..Metformin did not affect ozone-induced inflammation in mice of either genotype. The results indicate that hyperglycemia is unlikely to account for the pulmonary phenotype of obese mice...

..Novel therapeutic strategies for treatment of the obese patient with asthma may result from an increased understanding of the mechanisms underlying this relationship...

..The purpose of this review is to evaluate recent data addressing this relationship and its biological basis, and to evaluate the implications of these data for treatment...

..Our results indicate that TNF contributes to the AHR but not the PMN emigration induced by acute O(3) exposure. Keywords: whole body plethysmography; polymorphonuclear leukocytes; minute ventilation; knockout mice; methacholine..

..Chamber studies in adult humans indicate reduced responses to acute ozone with increasing age. Age-related changes in TNFα have been observed. TNFα induced inflammation is predominantly mediated through TNFR1...

..The results also indicate that the more pronounced effect of O3 on BAL neutrophils in Cap-treated rats is not the result of a greater inhaled dose of O3 resulting from greater VE...

..These data suggest that increased nitric oxide in the airways has no proinflammatory effects per se and may have beneficial effects on pulmonary function...

..Overexpression of ESE-3 protein in 3T3 cells and human bronchial smooth muscle cells inhibits MMP-1 promoter activity, suggesting that ESE-3 may function as a transcriptional repressor...

..Our results also demonstrate that changes in the lung tissue rather than the airways account for the amplification of O(3)-induced hyperresponsiveness observed in obese mice...

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..Our results indicate that IL-6 and OSM are capable of inducing signaling in HASM cells. In addition, OSM and IL-1beta synergistically cause COX-2 expression and PGE(2) release...

..This last finding may account for the unique inability of asthmatic patients to reverse spontaneous airways obstruction with a deep inspiration...

..These data suggest O3 exposure does not affect MCh responses in conducting airways; rather, it affects responses of peripheral contractile elements to MCh, without changing their maximal response...

..The next major challenge is to understand how they function in an integrated fashion...

..The data suggest that the simultaneous release in the airway, of even very small amounts of cytokines, can have important functional consequences...

..We propose that these direct effect of IL-13 on HASM cells may contribute at least in part to the airway narrowing observed in patients with asthma...

..Ovalbumin-induced changes in lavage interleukin-13, interleukin-5 and lymphocytes were also reduced in ROCK1(+/-) mice. In conclusion, both ROCK1 and ROCK2 are important in regulating allergic airway responses...

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..These effects of fasting are the result of declines in serum leptin. The mechanistic basis for this protective effect of leptin in fasted mice remains to be determined but is not related to effects on ozone-induced inflammation...

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..In addition, these results suggest that the induction of IL-6 via IL-1RI may be important in mediating the effects of O(3) during subacute exposure...

..Epidemiologic data indicate an increased incidence of asthma in the obese...

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..Taken together, these findings suggest that metformin, probably through activation of AMPK, reduces the rate of ongoing reorganization of the CSK and inhibits ASM cell proliferation...

..However, mice with DIO must remain obese for an extended period of time before this pulmonary phenotype is observed...

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..We conclude that the T allele of C-509T is associated with the diagnosis of asthma and may enhance TGF-beta1 gene transcription...

..Differences between ob/ob mice, which lack leptin, and db/db mice, which lack Ob-R(b) but not Ob-R(a), suggest leptin, acting through Ob-R(a), can modify some pulmonary responses to O(3)...

..Taken together, these results show that phosphorylated HSP27 favors reduced bead motions that are probably due to stabilization of the actin cytoskeleton...

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..Although EGR-1 is induced by PDGF in human airway smooth muscle cells in cell culture, the role of EGR-1 in airway remodeling and asthma remains to be established...

..These results indicate CXCR2 is essential for maximal neutrophil recruitment, epithelial cell sloughing, and persistent increases in MCh responsiveness after an acute O(3) exposure...

..Our results indicate that IL-6 deficiency reduces airway neutrophilia, as well as the levels of BALF sTNFR1 and sTNFR2 following acute high dose and/or subacute low-dose O(3) exposure, but has no effect on O(3)-induced AHR...

..Our results indicate that airway smooth muscle is a target for IL-9 and that IL-9 amplifies the potential for these cells to recruit eosinophils and neutrophils into the airways by a mechanism involving ERK...

..This is the first description of a role for OSM on IL-1R1 expression in any cell type. OSM may contribute to airway remodeling observed in chronic airway disease...

..Eotaxin is implicated in asthmatic eosinophilia. Oncostatin M (OSM) causes eotaxin release from fibroblasts...

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..These results also suggest that chronic systemic inflammation may enhance airway responses to O3 in obese mice...

..Our data suggest that IL-4 and IL-13 mediate their effects on VEGF expression post-transcriptionally and indicate that polymorphisms in the VEGF, but not the IL-4R alpha, gene affect VEGF release from smooth muscle cells...

..Understanding the mechanistic basis for the effects of these cytokines may prove to be an important step in improving the efficacy of beta-agonists for the treatment of asthma...

..Moreover, obesity-related differences in activation of STAT proteins may contribute to some of the differences in the response of obese vs. lean mice...

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..Thus, the ROCK pathway may be an important and still relatively unexplored therapeutic target in asthma. Understanding the role of ROCKs in mouse models of asthma could lead to new strategies for preventing this disease. ..

..The focus of our research is a hormone produced by fat cells. Understanding the relationship between obesity and asthma could lead to new strategies for treating asthma, particularly in patients who are overweight or obese. ..

..Understanding the mechanistic basis for the augmented pulmonary responses to air pollution may lead to therapeutic strategies for reductions in responses to air pollution in this at risk population. ..

..The focus of our research is a hormone produced by fat cells. Understanding the relationship between obesity and asthma could lead to new strategies for treating asthma, particularly in patients who are overweight or obese. ..

..The focus of our research is a hormone produced by fat cells. Understanding the relationship between obesity and asthma could lead to new strategies for treating asthma, particularly in patients who are overweight or obese. ..

..Understanding the mechanistic basis for the augmented pulmonary responses to air pollution may lead to new therapeutic strategies for this increasingly at risk population. ..