IL-1b and TNF-a induce increased expression of CCL28 by airway epithelial cells via an NFjB-dependent pathway

CCL28 is a mucosal chemokine that attracts eosinophils and T cells via the receptors CCR3 and CCR10. Consequently, it is a candidate mediator of the pathology associated with asthma. This study examined constitutive and induced expression of CCL28 by A549 human airway epithelial-like cells. Real-time RT-PCR and ELISA of cultured cells and supernatants revealed constitutive levels of CCL28 expression to be low, whereas IL-1b and TNF-a, induced signiï¬cantly increased expression. Observations from induced sputum and human airway biopsies supported this. Signal transduction studies revealed that IL-1b and TNF-a stimulation induced NFjB phosphorylation in A549 cells, but antagonist inhibition of NFjB p50âp65 phosphorylation correlated with marked reduction of IL-1b or TNF-a induced CCL28 expression. Together these studies imply a role for CCL28 in the orchestration of airway inï¬ammation, and suggest that CCL28 is one link between microbial insult and the exacerbation of pathologies such as asthma, through an NFjB-dependent mechanism

Use of a Cybex NORM dynamometer to assess muscle function in patients with thoracic cancer

<p>Abstract</p> <p>Background</p> <p>The cachexia-anorexia syndrome impacts on patients' physical independence and quality of life. New treatments are required and need to be evaluated using acceptable and reliable outcome measures, e.g. the assessment of muscle function. The aims of this study were to: (i) examine the acceptability and reliability of the Cybex NORM dynamometer to assess muscle function in people with non-small cell lung cancer or mesothelioma; (ii) compare muscle function in this group with healthy volunteers and; (iii) explore changes in muscle function over one month.</p> <p>Methods</p> <p>The test consisted of 25 repetitions of isokinetic knee flexion and extension at maximal effort while seated on a Cybex NORM dynamometer. Strength and endurance for the quadriceps and hamstrings were assessed as peak torque and total work and an endurance ratio respectively. Thirteen patients and 26 volunteers completed the test on three separate visits. Acceptability was assessed by questionnaire, reliability by intraclass correlation coefficients (ICC) and tests of difference compared outcomes between and within groups.</p> <p>Results</p> <p>All subjects found the test acceptable. Peak torque and work done were reliable measures (ICC >0.80), but the endurance ratio was not. Muscle function did not differ significantly between the patient and a matched volunteer group or in either group when repeated after one month.</p> <p>Conclusion</p> <p>For patients with non-small cell lung cancer or mesothelioma, the Cybex NORM dynamometer provides an acceptable and reliable method of assessing muscle strength and work done. Muscle function appears to be relatively well preserved in this group and it appears feasible to explore interventions which aim to maintain or even improve this.</p

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

IL-1b and TNF-a induce increased expression of CCL28 by airway epithelial cells via an NFjB-dependent pathway

CCL28 is a mucosal chemokine that attracts eosinophils and T cells via the receptors CCR3 and CCR10. Consequently, it is a candidate mediator of the pathology associated with asthma. This study examined constitutive and induced expression of CCL28 by A549 human airway epithelial-like cells. Real-time RT-PCR and ELISA of cultured cells and supernatants revealed constitutive levels of CCL28 expression to be low, whereas IL-1b and TNF-a, induced signiï¬cantly increased expression. Observations from induced sputum and human airway biopsies supported this. Signal transduction studies revealed that IL-1b and TNF-a stimulation induced NFjB phosphorylation in A549 cells, but antagonist inhibition of NFjB p50âp65 phosphorylation correlated with marked reduction of IL-1b or TNF-a induced CCL28 expression. Together these studies imply a role for CCL28 in the orchestration of airway inï¬ammation, and suggest that CCL28 is one link between microbial insult and the exacerbation of pathologies such as asthma, through an NFjB-dependent mechanism

IL-1b and TNF-a induce increased expression of CCL28 by airway epithelial cells via an NFjB-dependent pathway

CCL28 is a mucosal chemokine that attracts eosinophils and T cells via the receptors CCR3 and CCR10. Consequently, it is a candidate mediator of the pathology associated with asthma. This study examined constitutive and induced expression of CCL28 by A549 human airway epithelial-like cells. Real-time RT-PCR and ELISA of cultured cells and supernatants revealed constitutive levels of CCL28 expression to be low, whereas IL-1b and TNF-a, induced signiï¬cantly increased expression. Observations from induced sputum and human airway biopsies supported this. Signal transduction studies revealed that IL-1b and TNF-a stimulation induced NFjB phosphorylation in A549 cells, but antagonist inhibition of NFjB p50âp65 phosphorylation correlated with marked reduction of IL-1b or TNF-a induced CCL28 expression. Together these studies imply a role for CCL28 in the orchestration of airway inï¬ammation, and suggest that CCL28 is one link between microbial insult and the exacerbation of pathologies such as asthma, through an NFjB-dependent mechanism

IL-1b and TNF-a induce increased expression of CCL28 by airway epithelial cells via an NFjB-dependent pathway

CCL28 is a mucosal chemokine that attracts eosinophils and T cells via the receptors CCR3 and CCR10. Consequently, it is a candidate mediator of the pathology associated with asthma. This study examined constitutive and induced expression of CCL28 by A549 human airway epithelial-like cells. Real-time RT-PCR and ELISA of cultured cells and supernatants revealed constitutive levels of CCL28 expression to be low, whereas IL-1b and TNF-a, induced signiï¬cantly increased expression. Observations from induced sputum and human airway biopsies supported this. Signal transduction studies revealed that IL-1b and TNF-a stimulation induced NFjB phosphorylation in A549 cells, but antagonist inhibition of NFjB p50âp65 phosphorylation correlated with marked reduction of IL-1b or TNF-a induced CCL28 expression. Together these studies imply a role for CCL28 in the orchestration of airway inï¬ammation, and suggest that CCL28 is one link between microbial insult and the exacerbation of pathologies such as asthma, through an NFjB-dependent mechanism

Suppression of type 2 immunity and allergic airway inflammation by secreted products of the helminth Heligmosomoides polygyrus:Immunomodulation

Allergic asthma is less prevalent in countries with parasitic helminth infections, and mice infected with parasites such as Heligmosomoides polygyrus are protected from allergic airway inflammation. To establish whether suppression of allergy could be mediated by soluble products of this helminth, we tested H. polygyrus excretory-secretory (HES) material for its ability to impair allergic inflammation. When HES was added to sensitising doses of ovalbumin, the subsequent allergic airway response was suppressed, with ablated cell infiltration, a lower ratio of effector (CD4(+)CD25(+)Foxp3(−)) to regulatory (CD4(+)Foxp3(+)) T (Treg) cells, and reduced Th1, Th2 and Th17 cytokine production. HES exposure reduced IL-5 responses and eosinophilia, abolished IgE production, and inhibited the type 2 innate molecules arginase-1 and RELM-α. Although HES contains a TGF-β-like activity, similar effects in modulating allergy were not observed when administering mammalian TGF-β alone. HES also protected previously sensitised mice, suppressing recruitment of eosinophils to the airways when given at challenge, but no change in Th or Treg cell populations was apparent. Because heat-treatment of HES did not impair suppression at sensitisation, but compromised its ability to suppress at challenge, we propose that HES contains distinct heat-stable and heat-labile immunomodulatory molecules which modulate pro-allergic adaptive and innate cell populations