Exercise reverses OVA‐induced inhibition of glucocorticoid receptor and increases anti‐inflammatory cytokines in asthma

Abstract

The purpose of this study was to determine the effect of aerobic exercise training (AT) on the expression of glucocorticoid receptors (GR) and anti-inflammatory cytokines in an asthma model. BALB/c mice were divided into groups control (CT; nonsensitized/nontrained), aerobic training (AT; nonsensitized/trained), ovalbumin (OVA; sensitized/not trained), and OVA+AT (sensitized/trained). OVA groups received OVA by inhalation, and the AT groups completed 1, 3, or 7 days of exercise (60 min/session). Expression of GR, IL-4, IL-5, IL-10, IL-1ra, NF-κB, TGF-β, VEGF, ICAM-1, VCAM-1; eosinophils counting; and airway remodeling (AR) features [airway smooth muscle (ASM) and epithelial thickness and collagen fiber deposition] were quantified. OVA sensitization induced a decrease in the expression of GR and increases in the eosinophil, IL-4, IL-5, NF-κB, TGF-β, VEGF, ICAM-1, VCAM-1, and AR features (P < 0.05). After 3 days, AT reversed the OVA-induced reduction in the expression of GR, and subsequently induced increases in the expression of IL-10 and IL-1ra (seventh day). In contrast, the eosinophil migration, the expression of NF-κB, IL-4, IL-5, TGF-β, RANTES, VEGF, ICAM-1, VCAM-1, and the AR features (P < 0.05) were reduced. AT increases the expression of GR and anti-inflammatory cytokines (IL-10 and IL-1ra) and reduces the expression of inflammatory mediators and airway inflammation in an animal model of asthma.

Repeated Allergen Exposure in A/J Mice Causes Steroid-Insensitive Asthma via a Defect in Glucocorticoid Receptor Bioavailability

“…Interestingly, in a pediatric asthma cohort, cells recovered from poor GC responders displayed lower GCR protein levels as compared with good GC responders (39). In this study, when the GCR level in lung homogenates was assessed using Western blot assays, we observed that repeated exposure of allergens on 2 or 4 consecutive d downregulated GCR expression in samples from A/J mice, in line with a previous report (40). Moreover, the reduction in lung tissue GCR protein levels was clearly impaired by dexamethasone given 1 h before provocation in the mice exposed to FIGURE 7.…”

Physical Activity: A Missing Link in Asthma Care

“…Potential mediating mechanisms include reductions in the serum T helper 2 proinflammatory cytokines interleukin (IL)-4, IL-5, and IL-6, IL-13-16, reductions in the monocyte chemoattractant protein 1 and keratinocyte chemoattractant protein (murine homologue to human IL-8), inhibition of nuclear factor kappa B (NFκB) activation, and increases in the anti-inflammatory cytokine IL-10, IL-1ra and circulating regulatory T cells. [84,[106][107][108][109]. Increased PADL was also associated with lower systemic inflammation (for every increase of 1000 steps per day, high sensitivity-CRP was reduced by 17%) in patients with severe asthma after adjustment for confounders, albeit no associations were found with measures of eosinophilic airway inflammation [31].…”

Interactions between osteopontin and vascular endothelial growth factor: Implications for cancer

“…In the absence of OPN, the exposure to allergen causes lesser lung fibroblast proliferation, reduced collagen deposition, diminished inflammatory cell accumulation, and decreased expression of VEGF, TGF-β and MMP-2 than is the case in OPN competent hosts [17]. Aerobic training in asthma reduces the levels of inflammatory mediators and proteins associated with the induction of airway remodeling, including OPN and VEGF, thus preserving airway integrity [159]. Within hours of infection with Mycobacterium tuberculosis, macrophages express genes involved in cell homing, including interleukin-8 and OPN.…”