Impact Of Adiponectin Overexpression On Allergic Airways Responses In Mice

Verbout, Norah G.; Hug, Christopher; Si, Huiqing; Shore, Stephanie A.

doi:10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a5189

Cited by 3 publications

(5 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, adiponectin, an antiinflammatory mediator that is decreased in obesity, functions in lean mice to inhibit allergic airway inflammation and airway reactivity (45,46), an activity that appears to be related to its serum levels (47). Conversely, leptin, an adipokine that is elevated in obesity, can increase airway reactivity and serum IgE in an allergic mouse model (48).…”

Section: Pre-existing Asthma Complicated By 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

View full text Add to dashboard Cite

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.

show abstract

Section: Pre-existing Asthma Complicated By 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

View full text Add to dashboard Cite

show abstract

“…Starting on day 12, mice were challenged weekly for 4 weeks by i.n. instillation of either sterile PBS or OVA (20 lg in 30 lL PBS) as previously described [24]. Mice were studied 24 h after the last OVA or PBS challenge.…”

Section: Allergen Sensitization and Challengementioning

confidence: 99%

“…We used real-time PCR and SYBR Green (Applied Biosystems, Foster City, CA, USA) to assess mRNA expression for each of the following genes: Retnla (resistinlike 1 alpha), Itln1 (intelectin 1), Muc5ac, and Clca3 (Gob5). Primers have been previously described [24]. Gene expression values were normalized to 18 s and expressed relative to WT PBS values, using the DDC t method [35].…”

Section: Rna Extraction and Real-time Pcrmentioning

confidence: 99%

Abrogation of airway hyperresponsiveness but not inflammation by rho kinase insufficiency

Kasahara¹,

Ninin²,

Wurmbrand³

et al. 2015

Clin Experimental Allergy

Self Cite

View full text Add to dashboard Cite

Background Major features of allergic asthma include airway hyperresponsiveness (AHR), eosinophilic inflammation, and goblet cell metaplasia. Rho kinase (ROCK) is a serine/threonine protein kinase that regulates the actin cytoskeleton. By doing so, it can modulate airway smooth muscle cell contraction and leukocyte migration and proliferation. This study was designed to determine the contributions of the two ROCK isoforms, ROCK1 and ROCK2, to AHR, inflammation and goblet cell metaplasia in a mast-cell dependent model of allergic airways disease. Methods and Results Repeated intranasal challenges with OVA caused AHR, eosinophilic inflammation, and goblet cell hyperplasia in wildtype (WT) mice. OVA-induced AHR was partially or completely abrogated in mice haploinsufficient for ROCK2 (ROCK2+/−) or ROCK1 (ROCK1+/−), respectively. In contrast, there was no effect of ROCK insufficiency on allergic airways inflammation, although both ROCK1 and ROCK2 insufficiency attenuated mast cell degranulation. Goblet cell hyperplasia, as indicated by PAS staining, was not different in ROCK1+/− versus WT mice. However, in ROCK2+/− mice, goblet cell hyperplasia was reduced in medium but not large airways. Maximal acetylcholine-induced force generation was reduced in tracheal rings from ROCK1+/− and ROCK2+/− versus WT mice. The ROCK inhibitor, fasudil, also reduced airway responsiveness in OVA-challenged mice, without affecting inflammatory responses. Conclusion In a mast cell model of allergic airways disease, ROCK1 and ROCK2 both contribute to AHR, likely through direct effects on smooth muscle cell and effects on mast-cell degranulation. In addition, ROCK2 but not ROCK1 plays a role in allergen-induced goblet cell hyperplasia.

show abstract

“…In the first cohort, four‐ to five‐week‐old WT and ROCK2 +/− mice were sensitized to ovalbumin (OVA, Grade V; Sigma‐Aldrich Co., St. Louis, MO, USA) by i.p. injection with alum (Imject; Pierce‐Thermo Fisher Scientific, Rockford, Il, USA) on days 0 and 14 as previously described (see Fig. a for schematic).…”

Section: Methodsmentioning

confidence: 99%

“…The left lung was harvested and RNA prepared and reverse‐transcribed for real‐time PCR as previously described . Primers for murine Muc5ac and 18S ribosomal RNA were previously described . Muc5ac mRNA abundance relative to 18S was calculated based on the ΔΔCT method.…”

Section: Methodsmentioning

confidence: 99%

Role of ROCK2 in CD4⁺ cells in allergic airways responses in mice

Kasahara¹,

Mathews²,

Ninin³

et al. 2017

Clin Experimental Allergy

View full text Add to dashboard Cite

Background Rho kinases (ROCKs) contribute to allergic airways disease. ROCKs also play a role in lymphocyte proliferation and migration. Objective To determine the role of ROCK2 acting within CD4+ cells in allergic airways responses. Methods ROCK2 haploinsufficient (ROCK2+/-) and wildtype mice were sensitized with ovalbumin (OVA). ROCK2+/- mice then received either CD4+ cells from ROCK2 sufficient OVA TCR transgenic (OT-II) mice or saline i.v. 48 hours before challenge with aerosolized OVA. Wildtype mice received saline before challenge. Allergic airway responses were measured 48 hours after the last challenge. Allergic airways responses were also assessed in mice lacking ROCK2 only in CD4+ cells (ROCK2CD4Cre mice) versus control (CD4-Cre and ROCK2flox/flox) mice. Results OVA-induced increases in bronchoalveolar lavage lymphocytes, eosinophils, IL-13, IL-5, and eotaxin were reduced in ROCK2+/- versus wildtype mice, as were airway hyperresponsiveness and mucous hypersecretion. In ROCK2+/- mice, adoptive transfer with CD4+ cells from OT-II mice restored effects of OVA on lymphocytes, eosinophils, IL-13, IL-5, and mucous hypersecretion to wildtype levels, whereas eotaxin and airway hyperrresponsiveness were not affected. ROCK2 inhibitors reduced IL-13-induced release of eotaxin from airway smooth muscle (ASM), similar to effects of these inhibitors on ASM contractility. Despite the ability of adoptive transfer to restore allergic airways inflammation in ROCK2 insufficient mice, allergic inflammation was not different in ROCK2CD4Cre versus control mice. Conclusion ROCK2 contributes to allergic airways responses likely via effects within ASM cells and within non lymphocyte cells involved in lymphocyte activation and migration into the airways.

show abstract

Impact Of Adiponectin Overexpression On Allergic Airways Responses In Mice

Cited by 3 publications

References 29 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

Abrogation of airway hyperresponsiveness but not inflammation by rho kinase insufficiency

Role of ROCK2 in CD4⁺ cells in allergic airways responses in mice

Contact Info

Product

Resources

About

Impact Of Adiponectin Overexpression On Allergic Airways Responses In Mice

Cited by 3 publications

References 29 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

Abrogation of airway hyperresponsiveness but not inflammation by rho kinase insufficiency

Role of ROCK2 in CD4+ cells in allergic airways responses in mice

Contact Info

Product

Resources

About

Role of ROCK2 in CD4⁺ cells in allergic airways responses in mice