Fig 3 - available from: Inflammation Research
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![PGE 2 induces MKP-1 and TTP mRNA expression in a temporally specific manner. Growth-arrested ASM cells were treated with PGE 2 (100 nM) for 0, 1, 2, 4, 8, and 24 h. a MKP-1 and b TTP mRNA expression was quantified by real-time RT-PCR (results expressed as fold increase compared to vehicletreated cells at 0 h). Statistical analysis was performed using one-way ANOVA and then Fisher's PLSD post-test [where * denotes a significant increase compared to 0 h (P < 0.05)]. Data are mean + SEM values from n = 6 primary ASM cell cultures](publication/331634797/figure/fig1/AS:767946133618689@1560104034338/PGE-2-induces-MKP-1-and-TTP-mRNA-expression-in-a-temporally-specific-manner.png)
PGE 2 induces MKP-1 and TTP mRNA expression in a temporally specific manner. Growth-arrested ASM cells were treated with PGE 2 (100 nM) for 0, 1, 2, 4, 8, and 24 h. a MKP-1 and b TTP mRNA expression was quantified by real-time RT-PCR (results expressed as fold increase compared to vehicletreated cells at 0 h). Statistical analysis was performed using one-way ANOVA and then Fisher's PLSD post-test [where * denotes a significant increase compared to 0 h (P < 0.05)]. Data are mean + SEM values from n = 6 primary ASM cell cultures
Source publication
Tristetraprolin (TTP) is an anti-inflammatory molecule known to post-transcriptionally regulate cytokine production and is, therefore, an attractive drug target for chronic respiratory diseases driven by inflammation, such as asthma and chronic obstructive pulmonary disease. Our recent in vitro studies in primary human airway smooth (ASM) cells hav...
Contexts in source publication
Context 1
... the effect of PGE 2 (100 nM) on TTP mRNA expression in ASM cells. This was compared to a complete time-course for MKP-1 mRNA expression over a 24 h period, as our previous publication [14] solely focussed on MKP-1 mRNA expression at one time point only [i.e., 1 h, where 100 nM PGE 2 increased MKP-1 mRNA by 11.9 ± 3.3-fold (P < 0.05)]. As shown in Fig. 3a, 100 nM PGE 2 induced a rapid and significant peak of MKP-1 mRNA expression at 1 h (14.8 ± 4.1-fold: P < 0.05) and remained significantly upregulated at 2 h, but then subsided at 4 h and remained at basal levels at 8 h and 24 h. Interestingly, in Fig. 3b, we show, for the first time, in ASM cells, that PGE 2 induced a small, but ...
Context 2
... 1 h, where 100 nM PGE 2 increased MKP-1 mRNA by 11.9 ± 3.3-fold (P < 0.05)]. As shown in Fig. 3a, 100 nM PGE 2 induced a rapid and significant peak of MKP-1 mRNA expression at 1 h (14.8 ± 4.1-fold: P < 0.05) and remained significantly upregulated at 2 h, but then subsided at 4 h and remained at basal levels at 8 h and 24 h. Interestingly, in Fig. 3b, we show, for the first time, in ASM cells, that PGE 2 induced a small, but significant, increase in the expression of TTP mRNA at 1 h (P < ...
Citations
... PGE 2 also inhibited fibroblast migration, proliferation, collagen deposition, and myofibroblast differentiation in the lung (55). In vitro, PGE 2 decreased the expression of tenacin C and fibronectin by human fibroblast and ASM cells (56), reduced the proliferation of ASM cells derived from asthmatic patients (57), and upregulated the expression of the anti-inflammatory protein tristetraprolin in human ASM cells (58). Prior investigations of our group revealed that the instillation of glucagon induced a high production of PGE 2 into the lungs (59). ...
Asthma represents one of the leading chronic diseases worldwide and causes a high global burden of death and disability. In asthmatic patients, the exacerbation and chronification of the inflammatory response are often related to a failure in the resolution phase of inflammation. We reviewed the role of the main arachidonic acid (AA) specialized pro-resolving mediators (SPMs) in the resolution of chronic lung inflammation of asthmatics. AA is metabolized by two classes of enzymes, cyclooxygenases (COX), which produce prostaglandins (PGs) and thromboxanes, and lypoxygenases (LOX), which form leukotrienes and lipoxins (LXs). In asthma, two primary pro-resolving derived mediators from COXs are PGE2 and the cyclopentenone prostaglandin15-Deoxy-Delta-12,14-PGJ2 (15d-PGJ2) while from LOXs are the LXA4 and LXB4. In different models of asthma, PGE2, 15d-PGJ2, and LXs reduced lung inflammation and remodeling. Furthermore, these SPMs inhibited chemotaxis and function of several inflammatory cells involved in asthma pathogenesis, such as eosinophils, and presented an antiremodeling effect in airway epithelial, smooth muscle cells and fibroblasts in vitro. In addition, PGE2, 15d-PGJ2, and LXs are all able to induce macrophage reprogramming to an alternative M2 pro-resolving phenotype in vitro and in vivo. Although PGE2 and LXA4 showed some beneficial effects in asthmatic patients, there are limitations to their clinical use, since PGE2 caused side effects, while LXA4 presented low stability. Therefore, despite the strong evidence that these AA-derived SPMs induce resolution of both inflammatory response and tissue remodeling in asthma, safer and more stable analogs must be developed for further clinical investigation of their application in asthma treatment.
Asthma is the most common airway chronic disease with treatments aimed mainly to control the symptoms. Adrenergic receptor agonists, corticosteroids and anti-leukotrienes have been used for decades, and the development of more targeted asthma treatments, known as biological therapies, were only recently established. However, due to the complexity of asthma and the limited efficacy as well as the side effects of available treatments, there is an urgent need for a new generation of asthma therapies. The anti-inflammatory and bronchodilatory effects of prostaglandin E2 in asthma are promising, yet complicated by undesirable side effects, such as cough and airway irritation. In this review, we summarize the most important literature on the role of all four E prostanoid (EP) receptors on the lung's immune and structural cells to further dissect the relevance of EP2/EP4 receptors as potential targets for future asthma therapy.
Asthma is the most common airway chronic disease with treatments aimed mainly to control the symptoms. Adrenergic receptor agonists, corticosteroids and anti-leukotrienes have been used for decades, and the development of more targeted asthma treatments, known as biological therapies, were only recently established. However, due to the complexity of asthma and the limited efficacy as well as the side effects of available treatments, there is an urgent need for a new generation of asthma therapies. The anti-inflammatory and bronchodilatory effects of prostaglandin E2 in asthma are promising, yet complicated by undesirable side effects, such as cough and airway irritation. In this review, we summarize the most important literature on the role of all four E prostanoid (EP) receptors on the lung's immune and structural cells to further dissect the relevance of EP2/EP4 receptors as potential targets for future asthma therapy.
