Modulation of human airway smooth muscle biology by human adipocytes

Amanda Giesler,Katherine Radford,Luke Janssen,Parameswaran Nair,Manali Mukherjee

doi:10.1186/s12931-018-0741-z

Amanda Giesler, Katherine Radford + Show 3 more

Open Access

https://doi.org/10.1186/s12931-018-0741-z

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Abstract

BackgroundAsthma and obesity, two growing epidemics worldwide, may share an underlying causal relationship. Airway hyperresponsiveness (AHR), a defining component of asthma, has been documented in both ‘obese’ animal models and non-asthmatic obese individuals. However, there is a paucity of evidence that obesity-derived factors directly affect human airway smooth muscles (ASM).MethodsExperiments were designed with primary ASM and adipocytes isolated from the same human tissue explants (n = 6). The modulatory effects of human adipocytes extracted from subcutaneous (extrathoracic) and visceral (intrathoracic) depots, on ASM biology was examined with respect to proliferation, migration, contractility and pro-inflammatory cytokine synthesis.ResultsAdipocyte-conditioned media as well as myocyte-adipocyte co-cultures failed to show any significant changes in the proliferative or migrational properties of the ASM. Adipocyte-conditioned media also had no effect on the contractility or relaxation of bovine tracheal muscle strips. In contrast, there was a moderate yet significant increase of IL-6 and eotaxin release by ASM incubated with adipocyte-conditioned media (P = 0.0035 and P = 0.0067, vs. control, respectively), thereby further consolidating the altered inflammatory state reported for both diseases.ConclusionWe report, for the first time, that adipocytes from either subcutaneous or visceral depots can trigger an inflammatory state in the ASM, with negligible modulatory effects on hyperplasia, hypertrophy or contractile properties.

Highlights

Asthma and obesity, two growing epidemics worldwide, may share an underlying causal relationship
Rasmussen and Hancox [6] in a recent review assessed the available literature on asthma and obesity, summarizing three plausible mechanisms that could explain the observed associations between the two chronic conditions; viz., (i) altered breathing mechanics in obese that contribute to the airway hyperresponsiveness (AHR), (ii) an underlying inflammatory pathway driven by adipose-secreted mediators or ‘adipokines’, and (iii) lifestyle changes
Airway smooth muscle cell proliferation The proliferation of human ASMCs was significantly increased in the presence of 10% Fetal bovine serum (FBS) (P = 0.0008 vs. serumfree control), while the intra-thoracic and extra-thoracic ‘conditioned’ media had no effect on their growth (Fig. 1a)

Summary

Introduction

Two growing epidemics worldwide, may share an underlying causal relationship. Airway hyperresponsiveness (AHR), a defining component of asthma, has been documented in both ‘obese’ animal models and non-asthmatic obese individuals. Increased AHR has been reported in non-asthmatic obese individuals [15] and in teenagers with high body mass index (BMI) [16]. While discussing their experimental diet-induced mouse models [17], Shore et al, commented that innate AHR was a characteristic feature of obese mice independent of the modality of obesity induction.

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