Effect of triiodothyronine-induced thyrotoxicosis on airway hyperresponsiveness

Hollingsworth, Helen M.; Pratter, Melvin R.; Dubois, J. M.; Braverman, L. E.; Irwin, Richard S.

doi:10.1152/jappl.1991.71.2.438

Cited by 6 publications

(2 citation statements)

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“…Persistent airway hyperresponsiveness is present in the majority of patients with chronic asthma and is considered to reflect airway remodeling (9). Studies on the effects of thyroid hormones on airway hyperresponsiveness in vivo have shown that mild thyreotoxicosis induced by 4 wk of treatment with T 3 does not affect lung function, exercise capacity, or airway hyperresponsiveness in asthmatic patients (20). Similarly, T 3 -induced hyperthyroidism does not affect airway reactivity or lung function in healthy volunteers (21).…”

Section: L304mentioning

confidence: 99%

l-Thyroxine promotes a proliferative airway smooth muscle phenotype in the presence of TGF-β1

Dekkers¹,

Naeimi²,

Bos³

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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Hypothyroidism may reduce, whereas hyperthyroidism may aggravate, asthma symptoms. The mechanisms underlying this relationship are largely unknown. Since thyroid hormones have central roles in cell growth and differentiation, we hypothesized that airway remodeling, in particular increased airway smooth muscle (ASM) mass, may be involved. To address this hypothesis, we investigated the effects of triiodothyronine (T3) and l-thyroxine (T4) in the absence and presence of the profibrotic transforming growth factor (TGF)-β1 on human ASM cell phenotype switching. T3 (1-100 nM) and T4 (1-100 nM) did not affect basal ASM proliferation. However, when combined with TGF-β1 (2 ng/ml), T4 synergistically increased the proliferative response, whereas only a minor effect was observed for T3. In line with a switch from a contractile to a proliferative ASM phenotype, T4 reduced the TGF-β1-induced contractile protein expression by ∼50%. Cotreatment with T3 reduced TGF-β1-induced contractile protein expression by ∼25%. The synergistic increase in proliferation was almost fully inhibited by the integrin αvβ3 antagonist tetrac (100 nM), whereas no significant effects of the thyroid receptor antagonist 1-850 (3 μM) were observed. Inhibition of MEK1/2, downstream of the integrin αvβ3, also inhibited the T4- and TGF-β1-induced proliferative responses. Collectively, the results indicate that T4, and to a lesser extent T3, promotes a proliferative ASM phenotype in the presence of TGF-β1, which is predominantly mediated by the membrane-bound T4 receptor αvβ3. These results indicate that thyroid hormones may enhance ASM remodeling in asthma, which could be of relevance for hyperthyroid patients with this disease.

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Section: L304mentioning

confidence: 99%

l-Thyroxine promotes a proliferative airway smooth muscle phenotype in the presence of TGF-β1

Dekkers¹,

Naeimi²,

Bos³

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Susceptibility to infections does not appear to increase with altered thyroid function, but the high incidence of hypothyroidism in septic patients may contribute to cardiovascular instability [67], however this susceptibility has not been related, to date, to altered leukocyte function. Hyperthyroidism may exacerbate the severity to and susceptibility to asthma [66], although this view is not universally accepted [68]. Hypothyroidism may ameliorate coexistent allergic reactions since thyroidectomized rats experience a less severe pulmonary inflammation upon antigen challenge, possibly due to lower levels of IgE antibody [69], and/or reduced production of superoxide production by alveolar macrophages and neutrophils [69,70].…”

Section: Thyroid Hormonesmentioning

confidence: 99%

Modulation of Neutrophil Function by Hormones

Mathison

2006

CIR

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Endocrine regulation of the neutrophilic component of innate immunity with a particular focus on the production of reactive oxygen species (ROS) is the subject of this review. Endocrine hormones contribute to neutrophil mediated pathology in several ways either by directly activating the cells, as is the case with an angiotensin activation of NADPH oxidase on neutrophils and monocytes to contribute to atherosclerosis, or by having biphasic effects depending upon the stage of systemic inflammation, i.e. in a hyper-inflammatory phase or a hypo-inflammatory or anergic state, as seen with growth hormone. Some factors, such as a novel anti-inflammatory peptide from salivary glands, the tripeptide FEG, and hypothalamic proline-rich peptide have more subtle effects and appear to negatively regulate the priming events required for neutrophil activation. Investigations on the impact and role of endocrine hormones on neutrophil function and ROS production have contributed to the understanding of the efficacy of some medications in treating inflammation, as is the case with the angiotensin receptor blockers, and should lead to the development of novel drugs that modulate innate immune system function and the severity of an inflammatory response.With the exception of a small number of anaerobic bacteria oxidation reactions are essential for life. Management of oxygen metabolism is a fine balance between necessary life support and the highly toxic effects of oxygen and its metabolites. In 1969 it was recognized that superoxide dismutase, a free radical scavenger, formed a part of the routine defense against endogenously generated reactive oxygen species (ROS) [1]. The significance of this observation became apparent 12 years later when superoxide radicals, produced by neutrophils, were identified as the responsible agents for the increased capillary permeability in the ischemic bowel [2]. In short order neutrophils superoxide anion and ROS moved to the forefront of biomedical sciences, where they were perceived predominately as molecular outlaws, posing as a major threat to health [3].Various therapies have been proposed to treat ROSmediated pathology from the use of antagonists of selectins and integrins to prevent neutrophilic infiltration into tissue [4], antioxidant vitamin therapy [5], macrolide antibiotics to inhibit the production of proinflammatory cytokines [6], reduction-oxidation (redox)-sensitive transcription factors [7,8], probiotics [9], peroxisome proliferator-activated receptor agonists and statins [10]. These therapies attempt to block either the activation of the cells responsible for generating excess ROS or the proximal mediators of the ROS-dependent inflammatory response.Another therapeutic strategy to manage ROS production is to modulate the endocrine factors signaling their generation, as occurs with angiotensin II type 1 (AT 1 ) receptor antagonists and angiotensin-converting enzyme (ACE) inhibitors [11,12]. However, little attention has been paid to using the body's natural defenses, offered by endoc...

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Thyroid Function and Exercise

Bernet¹,

Wartofsky²

2000

Sports Endocrinology

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Effect of triiodothyronine-induced thyrotoxicosis on airway hyperresponsiveness

Cited by 6 publications

References 0 publications

l-Thyroxine promotes a proliferative airway smooth muscle phenotype in the presence of TGF-β1

l-Thyroxine promotes a proliferative airway smooth muscle phenotype in the presence of TGF-β1

Modulation of Neutrophil Function by Hormones

Thyroid Function and Exercise

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