Pivotal role of IL-6 in the hyperinflammatory responses to subacute ozone in adiponectin-deficient mice

Kasahara, David I.; Kim, Hye Young; Mathews, Joel; Verbout, Norah G.; Williams, Alison S.; Wurmbrand, Allison P.; Ninin, Fernanda M. C.; Neto, Felippe Lazar; Benedito, Leandro A.P.; Hug, Christopher; Umetsu, Dale T.; Shore, Stephanie A.

doi:10.1152/ajplung.00235.2013

Cited by 21 publications

(22 citation statements)

References 67 publications

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“…Williams and colleagues showed that augmented airway inflammation and reactivity in obese mice in response to ozone depended on TNFa (22). Increased responses to subacute ozone exposure are also seen in adiponectin-deficient mice (adiponectin is decreased in obesity), and this appears to be related to signaling through IL-6 and IL-17A (76)(77)(78). The role of these mediators in increasing responses to ozone in obese individuals needs further exploration.…”

Section: Irritant-and Pollutioninduced Asthma In Obesitymentioning

confidence: 99%

Mechanisms of Asthma in Obesity. Pleiotropic Aspects of Obesity Produce Distinct Asthma Phenotypes

Dixon

Poynter

2016

Am J Respir Cell Mol Biol

129

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The majority of patients with severe or difficult-to-control asthma in the United States are obese. Epidemiological studies have clearly established that obese patients tend to have worse asthma control and increased hospitalizations and do not respond to standard controller therapy as well as lean patients with asthma. Less clear are the mechanistic underpinnings for the striking clinical differences between lean and obese patients with asthma. Because obesity is principally a disorder of metabolism and energy regulation, processes fundamental to the function of every cell and system within the body, it is not surprising that it affects the respiratory system; it is perhaps surprising that it has taken so long to appreciate how dysfunctional metabolism and energy regulation lead to severe airway disease. Although early investigations focused on identifying a common factor in obesity that could promote airway disease, an appreciation has emerged that the asthma of obesity is a manifestation of multiple anomalies related to obesity affecting all the different pathways that cause asthma, and likely also to de novo airway dysfunction. Consequently, all the phenotypes of asthma currently recognized in lean patients (which are profoundly modified by obesity), as well as those unique to one's obesity endotype, likely contribute to obese asthma in a particular individual. This perspective reviews what we have learned from clinical studies and animal models about the phenotypes of asthma in obesity, which show how specific aspects of obesity and altered metabolism might lead to de novo airway disease and profoundly modify existing airway disease.

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Section: Irritant-and Pollutioninduced Asthma In Obesitymentioning

confidence: 99%

Mechanisms of Asthma in Obesity. Pleiotropic Aspects of Obesity Produce Distinct Asthma Phenotypes

Dixon

Poynter

2016

Am J Respir Cell Mol Biol

129

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“…Cell suspensions from disaggregated lungs were stimulated with ionomycin and phorbol 12-myristate 13-acetate in the presence of GolgiStop (24,25). Cells were fixed, permeabilized, and stained for surface markers (CD45, CD3, CD4, CD69, and TCRd) and intracellular cytokines (IL-13 and IL-17), then analyzed (BD Canto II cytometer, BD DIVA, and FlowJo; BD Biosciences, San Jose, CA).…”

Section: Flow Cytometrymentioning

confidence: 99%

Repeated Mouse Lung Exposures toStachybotrys chartarumShift Immune Response from Type 1 to Type 2

Lichtenstein¹,

Molina²,

Donaghey³

et al. 2016

Am J Respir Cell Mol Biol

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After a single or multiple intratracheal instillations of Stachybotrys chartarum (S. chartarum or black mold) spores in BALB/c mice, we characterized cytokine production, metabolites, and inflammatory patterns by analyzing mouse bronchoalveolar lavage (BAL), lung tissue, and plasma. We found marked differences in BAL cell counts, especially large increases in lymphocytes and eosinophils in multipledosed mice. Formation of eosinophil-rich granulomas and airway goblet cell metaplasia were prevalent in the lungs of multiple-dosed mice but not in single-or saline-dosed groups. We detected changes in the cytokine expression profiles in both the BAL and plasma. Multiple pulmonary exposures to S. chartarum induced significant metabolic changes in the lungs but not in the plasma. These changes suggest a shift from type 1 inflammation after an acute exposure to type 2 inflammation after multiple exposures to S. chartarum. Eotaxin, vascular endothelial growth factor (VEGF), MIP-1a, MIP-1b, TNF-a, and the IL-8 analogs macrophage inflammatory protein-2 (MIP-2) and keratinocyte chemoattractant (KC), had more dramatic changes in multiplethan in single-dosed mice, and parallel the cytokines that characterize humans with histories of mold exposures versus unexposed control subjects. This repeated exposure model allows us to more realistically characterize responses to mold, such as cytokine, metabolic, and cellular changes.

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“…2). Moreover, both IL-6 and IL-17A have been shown to play a pivotal role in the pathogeneses of asthma in obese mice following a challenge with subacute ozone exposition [45,97]; however, the mechanism by which these interleukins directly trigger bronchoconstriction remains unknown. Both papers used genetic adiponectin-deficient mice, showing a possible correlation between adiponectin deficiency and low-grade inflammation in the lungs.…”

mentioning

confidence: 99%

Obesity and asthma: beyond TH2 inflammation

2015

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Pivotal role of IL-6 in the hyperinflammatory responses to subacute ozone in adiponectin-deficient mice

Cited by 21 publications

References 67 publications

Mechanisms of Asthma in Obesity. Pleiotropic Aspects of Obesity Produce Distinct Asthma Phenotypes

Mechanisms of Asthma in Obesity. Pleiotropic Aspects of Obesity Produce Distinct Asthma Phenotypes

Repeated Mouse Lung Exposures toStachybotrys chartarumShift Immune Response from Type 1 to Type 2

Obesity and asthma: beyond TH2 inflammation

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