Salbutamol increases tristetraprolin expression in macrophages

Jalonen, Ulla; Leppänen, Tiina; Kankaanranta, Hannu; Moilanen, Eeva

doi:10.1016/j.lfs.2007.09.022

Cited by 10 publications

(13 citation statements)

References 39 publications

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“…␤ 2 -Agonists have been reported to have antiinflammatory effects in various in vitro conditions but these actions do not clearly translate into the in vivo situation, e.g., in inflamed lung tissue in patients with asthma (Sitkauskiene and Sakalauskas, 2005). The mechanism described in the present study and in our earlier study (Jalonen et al, 2007) could, at least partly, explain the discrepancy between these in vitro and in vivo findings. In vivo, in situations with an ongoing inflammation, the expression of TTP can be down-regulated by ␤ 2 -agonists.…”

Section: Discussioncontrasting

confidence: 80%

“…We have recently shown that ␤ 2 -agonists, cAMP analogs, and forskolin increase TTP mRNA and protein expression in resting cells, possibly by increasing the activation of transcription factor activator protein 2 (Jalonen et al, 2007). In the present study, we found that TTP protein expression was differently regulated by cAMP-increasing compounds in cells exposed to LPS (which mimics the inflammatory situation) than in our earlier study in resting cells.…”

contrasting

confidence: 50%

“…We suggest that the degradation through the proteasome is an inducible mechanism to withdraw TTP from the cells and serves as a regulatory mechanism that enhances the inflammatory reaction by limiting the duration of TTP expression. Although the expression of TTP is regulated in a similar manner in resting mouse and human macrophages by cAMP-elevating agents (Jalonen et al, 2007), the results described in the present study require confirmation in human macrophages. Many factors increase intracellular cAMP levels through G-proteincoupled receptors in cell membrane, indicating that several Fig.…”

Section: Discussionmentioning

confidence: 46%

“…We recently reported that the expression of TTP mRNA and protein could be induced by ␤ 2 -agonists, cAMP analogs, and forskolin in resting macrophages, and that was probably mediated by increased activator protein 2 activation (Jalonen et al, 2007). Here, we have shown that when these compounds were given in combination with LPS, which mimics the inflammatory situation, TTP protein levels were significantly decreased.…”

Section: Discussionmentioning

confidence: 65%

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Compounds That Increase or Mimic Cyclic Adenosine Monophosphate Enhance Tristetraprolin Degradation in Lipopolysaccharide-Treated Murine J774 Macrophages

Jalonen¹,

Paukkeri²,

Moilanen³

2008

The Journal of Pharmacology and Experimental Therapeutics

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Tristetraprolin (TTP) is a trans-acting factor that can regulate mRNA stability by binding to the cis-acting AU-rich element (ARE) in the 3Ј-untranslated region in mRNAs of certain transiently expressed genes. The best-studied target of TTP is tumor necrosis factor (TNF)-␣. By binding to ARE, TTP increases the degradation of TNF-␣ mRNA, thereby reducing the expression of TNF-␣. We examined the effects of cAMP analogs and the cAMP-elevating agents forskolin and ␤ 2 -agonists on lipopolysaccharide (LPS)-induced TTP mRNA and protein expression by quantitative real-time reverse transcriptase-polymerase chain reaction and Western blotting in activated macrophages. All of these agents caused a slight increase in LPSinduced expression of TTP mRNA. However, TTP protein levels were significantly reduced when the cells were treated with the combination of LPS and cAMP-elevating agent compared with LPS alone.and lactacystin increased TTP protein levels and abolished the effects of cAMP-enhancing compounds on TTP protein levels. The results suggest that mediators and drugs that enhance intracellular cAMP reduce TTP expression in macrophages exposed to inflammatory stimuli by increasing TTP degradation through the proteasome pathway.

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Section: Discussioncontrasting

confidence: 80%

contrasting

confidence: 50%

Section: Discussionmentioning

confidence: 46%

Section: Discussionmentioning

confidence: 65%

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Compounds That Increase or Mimic Cyclic Adenosine Monophosphate Enhance Tristetraprolin Degradation in Lipopolysaccharide-Treated Murine J774 Macrophages

Jalonen¹,

Paukkeri²,

Moilanen³

2008

The Journal of Pharmacology and Experimental Therapeutics

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“…Inhibitor studies involving inhibition of NF-kB, in the presence of IL-1b and LPS, have shown that TTP mRNA is a direct substrate of the NF-kB signaling pathway (King et al, 2009;Chen et al, 2013). Other signaling pathways include the protein kinase C (PKC) pathway, via transcription factor activating protein 2, which was shown to regulate TTP mRNA in the presence of a phorbol ester (Chen et al, 1998;Tan and Parker, 2003;Jalonen et al, 2007;Leppänen et al, 2008Leppänen et al, , 2010 and the epidermal growth factor pathway, via the transcription factor ETS domain-containing protein ELK-1 (Florkowska et al, 2012).…”

Section: Ttp Function: Multiple Levels Of Regulatory Controlmentioning

confidence: 99%

Tristetraprolin and Its Role in Regulation of Airway Inflammation

Prabhala

Ammit

2015

Molecular Pharmacology

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Chronic inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are clinically and socioeconomically important diseases globally. Currently the mainstay of anti-inflammatory therapy in respiratory diseases is corticosteroids. Although corticosteroids have proven clinical efficacy in asthma, many asthmatic inflammatory conditions (e.g., infection, exacerbation, and severe asthma) are not responsive to corticosteroids. Moreover, despite an understanding that COPD progression is driven by inflammation, we currently do not have effective anti-inflammatory strategies to combat this disease. Hence, alternative anti-inflammatory strategies are required. p38 mitogen-activated protein kinase (MAPK) has emerged as an important signaling molecule driving airway inflammation, and pharmacological inhibitors against p38 MAPK may provide potential therapies for chronic respiratory disease. In this review, we discuss some of the recent in vitro and in vivo studies targeting p38 MAPK, but suggest that p38 MAPK inhibitors may prove less effective than originally considered because they may block antiinflammatory molecules along with proinflammatory responses. We propose that an alternative strategy may be to target an antiinflammatory molecule farther downstream of p38 MAPK, i.e., tristetraprolin (TTP). TTP is an mRNA-destabilizing, RNAbinding protein that enhances the decay of mRNAs, including those encoding proteins implicated in chronic respiratory diseases. We suggest that understanding the molecular mechanism of TTP expression and its temporal regulation will guide future development of novel anti-inflammatory pharmacotherapeutic approaches to combat respiratory disease.

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