Differential Cytokine Gene Expression in the Diaphragm in Response to Strenuous Resistive Breathing

Vassilakopoulos, Theodoros P.; Divangahi, Maziar; Rallis, George; Kishta, Osama A.; Petrof, Basil J.; Comtois, Alain Steve; Hussain, Sabah N. A.

doi:10.1164/rccm.200308-1071oc

Cited by 83 publications

(121 citation statements)

References 75 publications

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“…There were previously reported that OVA increased the breathing resistance of the mice [11], resistive breathing induced IL-4 expression in diaphragm muscle [12], Th2 cytokines such as IL-4 and IL-13 induce iNOS expression through the STAT-6 pathway [13][14][15][16][17], iNOS reduced diaphragm muscle contraction, inhibition of iNOS induction and inhibition of NOS activity prevented diaphragm muscle contractile dysfunction [18]. Study results of ours are in agreement with study that previously reported.…”

Section: Discussionsupporting

confidence: 93%

Diaphragm Muscle Contraction Decrease in a Mouse Model of Ovalbumin-Induced Allergic Airway Inflammation

Yamaguchi¹,

Shindoh²,

Miura³

2017

J Allergy Ther

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Objective: We investigated diaphragm contractile and inflammatory properties of mice with OVA sensitization and challenge.Methods: BALB/c mice were sensitized to OVA by intraperitoneal (i.p.) injection at 0 and 7 days, and challenged with aerosolized OVA on 21, 22, and 23 days (O/O group). Budesonide/Formoterol combination was inhaled on days 21, 22, and 23 before OVA challenge on those same days (O/OC group). Control mice were sensitized and challenged with an aerosolized saline (O-group). The diaphragm contractile and inflammatory properties were measured on day 24. NOS activity in the diaphragm muscle was evaluated by NADPH diaphorase staining. IL-4 and IL-13 levels of BALF, as well as lung tissue and diaphragm muscle homogenates were measured by ELISA. Conclusions:OVA sensitization and challenge decreased diaphragm muscle contraction, increased NOS activity, IL-4 levels of diaphragm in a mouse model. Budesonide/Formoterol combination could protect diaphragm muscle weakness and inflammation. According to the traditional concept of the contemporary Immunology, neither autoimmune diseases nor allergic diseases can be cured completely. Nevertheless, a fortunate coincidence led me to discovery of a novel concept that eliminations of the causes of these diseases are possible. In other words, combinations of pathogenic antibodies with responsible cells, namely, cytolytic T lymphocytes in cases of autoimmune diseases and mast cells in cases of allergic diseases, can be decomposed by replacing the pathogenic antibodies with non-specific antibodies. In more detail, intradermal injections with a non-specific antigen preparation induce production of non-specific antibodies in the body of the patient. Repetitions of the injections bring about an accumulation of them. Accumulated non-specific antibodies will occupy most of the receptors on the surface of responsible cells. When the accumulation reaches the sufficient level, virtually no pathogenic antibodies would remain on the receptors. That is, no causes of the diseases remain. Naturally, where there is no cause, there is no disease. Details are demonstrated elsewhere.

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Section: Discussionsupporting

confidence: 93%

Diaphragm Muscle Contraction Decrease in a Mouse Model of Ovalbumin-Induced Allergic Airway Inflammation

Yamaguchi¹,

Shindoh²,

Miura³

2017

J Allergy Ther

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“…The elevation in neutrophils and macrophages in the diaphragm in the present study is consistent with other observations after lengthening contractions of muscle [47,48], electrically stimulated contractions [49] and exposure of muscle to toxin or poison [41,42], but contrary to other recent reports [50,51]. Of these two differing reports, one described the extensor digitorum longus (EDL) muscle in response to in situ lengthening contractions [50] and the other investigated the diaphragm in response to resistive loading [51].…”

Section: Load-induced Diaphragm Inflammationsupporting

confidence: 91%

Granulocytosis and increased adhesion molecules after resistive loading of the diaphragm

Wang¹

2005

European Respiratory Journal

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Upregulation of endothelial cell adhesion molecules, followed by an influx of granulocytes and macrophages, can contribute to exertion-induced skeletal muscle injury. The purpose of this study was to quantify circulating leukocyte subsets, diaphragm injury and infiltrating leukocyte subsets, and surface expression of vascular cell adhesion molecule (VCAM)-1 and intracellular adhesion molecule (ICAM)-1 in the diaphragm after inspiratory resistive loading (IRL).Eight New Zealand white rabbits underwent 1.5 h of IRL and seven control rabbits underwent a sham procedure. Blood samples, taken at baseline and 2, 6, 12, 24, 48 and 72 h after the onset of IRL or sham, showed that band cell counts had increased at 6 h post-IRL. Point counting of haematoxylin and eosin-stained cross-sections, sampled at 72 h post-IRL, showed greater injury in diaphragms from IRL rabbits compared with controls. Immunohistochemical processing showed increased expression of ICAM-1 and VCAM-1, and higher granulocyte and macrophage counts in IRL diaphragms than control diaphragms. Macrophages were the predominant inflammatory cells.Increased intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression, and infiltration of granulocytes and macrophages may contribute to inspiratory resistive loadinginduced diaphragm injury.

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“…This view is based on the observations that strenuous resistive breathing and whole body exercise in healthy humans, such as treadmill running, induce signifi cant elevations of plasma pro-infl ammatory cytokine levels, including IL6, IL-1β, and TNFα and that this production is mediated in part by increased oxygen radical production (Vassilakopoulos et al 1999(Vassilakopoulos et al , 2002Ostrowski et al 1998). This role of ventilatory muscles as a source of systemic infl ammation has been confi rmed in an animal model of inspiratory resistive loading, where increased work of breathing signifi cantly upregulates IL6, IL1β and TNFα expressions within the diaphragm (Vassilakopoulos et al 2004). A recent study by Casadevall and colleagues (2007) has confi rmed that TNFα and IL6 levels are signifi cantly elevated in the intercostal muscles of COPD patients.…”

Section: Infl Ammationmentioning

confidence: 93%

Skeletal Muscle Dysfunction in Patients with Chronic Obstructive Pulmonary Disease

2010

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Chronic obstructive pulmonary disease (COPD) is a debilitating disease characterized by infl ammation-induced airfl ow limitation and parenchymal destruction. In addition to pulmonary manifestations, patients with COPD develop systemic problems, including skeletal muscle and other organ-specifi c dysfunctions, nutritional abnormalities, weight loss, and adverse psychological responses. Patients with COPD often complain of dyspnea on exertion, reduced exercise capacity, and develop a progressive decline in lung function with increasing age. These symptoms have been attributed to increases in the work of breathing and in impairments in gas exchange that result from airfl ow limitation and dynamic hyperinfl ation. However, there is mounting evidence to suggest that skeletal muscle dysfunction, independent of lung function, contributes signifi cantly to reduced exercise capacity and poor quality of life in these patients. Limb and ventilatory skeletal muscle dysfunction in COPD patients has been attributed to a myriad of factors, including the presence of low grade systemic infl ammatory processes, nutritional depletion, corticosteroid medications, chronic inactivity, age, hypoxemia, smoking, oxidative and nitrosative stresses, protein degradation and changes in vascular density. This review briefl y summarizes the contribution of these factors to overall skeletal muscle dysfunction in patients with COPD, with particular attention paid to the latest advances in the fi eld. Keywords: skeletal muscles, chronic obstructive pulmonary disease, diaphragm, quadriceps, fatigue, disuse, atrophy, smoking, exercise It has long been recognized that COPD is a systemic disease in which several extrapulmonary manifestations, including cachexia and skeletal muscle dysfunction, contribute to morbidity and mortality. Functionally, skeletal muscle dysfunction in COPD patients is characterized by signifi cant reduction in muscle strength and endurance. It is structurally characterized by loss of muscle mass and cross-sectional area (muscle atrophy), fi ber type distribution (reduction in the proportion of oxidative fi bers and increases in the proportion of glycolytic fi bers), oxidative metabolic capacity (attenuation of mitochondrial enzyme activities and expression) and capillary distribution (signifi cant loss of capillary density). Although disuse and inactivity are important contributors to the pathogenesis of skeletal muscle dysfunction in COPD patients, several other systemic and local factors are also involved. These include systemic infl ammation, malnutrition, corticosteroid usage, hypoxemia, aging, smoking and local factors such as the production of reactive oxygen (ROS) and nitrogen species (RNS) and enhanced protein degradation inside muscle fi bers, a result of increased activities of the proteasomal and lysosomal pathways and activation of calpains and caspases. Evidence of skeletal muscle dysfunction in patients with COPDIt has been well established that skeletal muscle function (strength and endurance) and s...

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Differential Cytokine Gene Expression in the Diaphragm in Response to Strenuous Resistive Breathing

Cited by 83 publications

References 75 publications

Diaphragm Muscle Contraction Decrease in a Mouse Model of Ovalbumin-Induced Allergic Airway Inflammation

Diaphragm Muscle Contraction Decrease in a Mouse Model of Ovalbumin-Induced Allergic Airway Inflammation

Granulocytosis and increased adhesion molecules after resistive loading of the diaphragm

Skeletal Muscle Dysfunction in Patients with Chronic Obstructive Pulmonary Disease

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