Brijeshkumar S. Patel

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Sphingosine 1-phosphate (S1P), a bioactive sphingolipid elevated in asthmatic airways, is increasingly recognized as playing an important role in respiratory disease. S1P activates receptor-mediated signaling to modulate diverse cellular functions and promote airway inflammation. Although many of the stimulatory pathways activated by S1P have been(More)
The xanthine doxofylline has been examined in clinical trials and shown to have efficacy and greater tolerability than theophylline in asthma and chronic obstructive pulmonary disease. The 'novofylline' doxofylline has demonstrated bronchodilatory and anti-inflammatory actions in in vivo and ex vivo experimental models of respiratory disease. However, there(More)
Corticosteroids are effective anti-inflammatory therapies widely utilized in chronic respiratory diseases. But these medicines can lose their efficacy during respiratory infection resulting in disease exacerbation. Further in vitro research is required to understand how infection worsens lung function control in order to advance therapeutic options to treat(More)
Roflumilast is an orally active phosphodiesterase 4 inhibitor approved for use in chronic obstructive pulmonary disease. Roflumilast N-oxide (RNO) is the active metabolite of roflumilast and has a demonstrated antiinflammatory impact in vivo and in vitro. To date, the effect of RNO on the synthetic function of airway smooth muscle (ASM) cells is unknown. We(More)
Protein phosphatase 2A (PP2A) activity can be enhanced pharmacologically by PP2A-activating drugs (PADs). The sphingosine analog FTY720 is the best known PAD and we have shown that FTY720 represses production of pro-inflammatory cytokines responsible for respiratory disease pathogenesis. Whether its phosphorylated form, FTY720-P, also enhances PP2A activity(More)
Mitogen activated protein kinase phosphatase-1 (MKP-1) has emerged as an important protein mediating breast cancer oncogenesis and chemoresistance to cancer chemotherapies, especially proteasome inhibitors. In this in vitro study, we utilized the breast cancer epithelial cell lines MCF-7 and MDA-MB-231, in comparison to MCF-10A control cells, to examine the(More)
Mitogen-activated protein kinase phosphatase 1 (MKP-1) represses MAPK-driven signalling and plays an important anti-inflammatory role in asthma and airway remodelling. Although MKP-1 is corticosteroid-responsive and increased by cAMP-mediated signalling, the upregulation of this critical anti-inflammatory protein by long-acting β2-agonists and(More)
BACKGROUND IL-17A plays an important role in respiratory disease and is a known regulator of pulmonary inflammation and immunity. Recent studies have linked IL-17A with exacerbation in asthma and COPD. We have shown that the enzyme cyclooxygenase-2 (COX-2) and its prostanoid products, prostaglandin E2 (PGE2 ) in particular, are key contributors in in vitro(More)
β2-agonists are principally used in asthma to provide bronchodilation; however, they also have antiinflammatory properties, due, in part, to their ability to up-regulate mitogen-activated protein kinase phosphatase (MKP) 1 in a cAMP-dependent manner. Phosphodiesterases (PDEs) are attractive targets for potentiating the antiinflammatory response. There are(More)