Asthma and chronic obstructive pulmonary disease (COPD) are obstructive airway disorders which differ in their underlying causes and phenotypes but overlap in patterns of pharmacological treatments. In both asthma and COPD, oxidative stress contributes to airway inflammation by inducing inflammatory gene expression. The redox-sensitive transcription factor, nuclear factor (NF)-kappaB (NF-κB), is an important participant in a broad spectrum of inflammatory networks that regulate cytokine activity in airway pathology. The anti-inflammatory actions of glucocorticoids (GCs), a mainstay treatment for asthma, involve inhibition of NF-κB induced gene transcription. Ligand bound GC receptors (GRs) bind NF-κB to suppress the transcription of NF-κB responsive genes (i.e., transrepression). However, in severe asthma and COPD, the transrepression of NF-κB by GCs is negated as a consequence of post-translational changes to GR and histones involved in chromatin remodeling. Therapeutics which target NF-κB activation, including inhibitors of IκB kinases (IKKs) are potential treatments for asthma and COPD. Furthermore, reversing GR/histone acetylation shows promise as a strategy to treat steroid refractory airway disease by augmenting NF-κB transrepression. This review examines NF-κB signaling in airway inflammation and its potential as target for treatment of asthma and COPD.

Fibrosis is the formation of fibrous connective tissue in response to injury. It is characterized by the accumulation of extracellular matrix components, particularly collagen, at the site of injury. Fibrosis is an adaptive response that is a vital component of wound healing and tissue repair. However, its continued activation is highly detrimental and a common final pathway of numerous disease states including cardiovascular and respiratory disease. Worldwide, fibrotic diseases cause over 800,000 deaths per year, accounting for ~45% of total deaths. With an aging population, the incidence of fibrotic disease and subsequently the number of fibrosis-related deaths will rise further. Although, fibrosis is a well-recognized cause of morbidity and mortality in a range of disease states, there are currently no viable therapies to reverse the effects of chronic fibrosis. Numerous predisposing factors contribute to the development of fibrosis. Biological aging in particular, interferes with repair of damaged tissue, accelerating the transition to pathological remodeling, rather than a process of resolution and regeneration. When fibrosis progresses in an uncontrolled manner, it results in the irreversible stiffening of the affected tissue, which can lead to organ malfunction and death. Further investigation into the mechanisms of fibrosis is necessary to elucidate novel, much needed, therapeutic targets. Fibrosis of the heart and lung make up a significant proportion of fibrosis-related deaths. It has long been established that the heart and lung are functionally and geographically linked when it comes to health and disease, and thus exploring the processes and mechanisms that contribute to fibrosis of each organ, the focus of this review, may help to highlight potential avenues of therapeutic investigation.

Early metastasis leads to poor prognosis of lung cancer patients, whose 5-year survival rate is only 15%. We could recently show that the Ca 2+ sensitive K + channel K Ca 3.1 promotes aggressive behavior of non-small cell lung cancer (NSCLC) cells and that it can serve as a prognostic marker in NSCLC. Since NSCLC patients die of metastases, we investigated whether K Ca 3.1 channels contribute to poor patient prognosis by regulating distinct steps of the metastatic cascade.

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia of unknown cause with a median survival of only three years. Little is known about the mechanisms that precede the excessive collagen deposition seen in IPF, but cellular senescence has been strongly implicated in disease pathology. Senescence is a state of irreversible cell-cycle arrest accompanied by an abnormal secretory profile and is thought to play a critical role in both development and wound repair. Normally, once a senescent cell has contributed to wound repair, it is promptly removed from the environment via infiltrating immune cells. However, if immune clearance fails, the persistence of senescent cells is thought to drive disease pathology through their altered secretory profile. One of the major cell types involved in wound healing is fibroblasts, and senescent fibroblasts have been identified in the lungs of patients with IPF and in fibroblast cultures from IPF lungs. The question of what is driving abnormally high numbers of fibroblasts into senescence remains unanswered. The transcription factor signal transducer and activator of transcription 3 (STAT3) plays a role in a myriad of processes, including cell-cycle progression, gene transcription, as well as mitochondrial respiration, all of which are dysregulated during senescence. Activation of STAT3 has previously been shown to correlate with IPF progression and therefore is a potential molecular target to modify early-stage senescence and restore normal fibroblast function. This review summarizes what is presently known about fibroblast senescence in IPF and how STAT3 may contribute to this phenotype.