2016
DOI: 10.1002/jcp.25327
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Corticosteroid‐Induced MKP‐1 Represses Pro‐Inflammatory Cytokine Secretion by Enhancing Activity of Tristetraprolin (TTP) in ASM Cells

Abstract: Exaggerated cytokine secretion drives pathogenesis of a number of chronic inflammatory diseases, including asthma. Anti-inflammatory pharmacotherapies, including corticosteroids, are front-line therapies and although they have proven clinical utility, the molecular mechanisms responsible for their actions are not fully understood. The corticosteroid-inducible gene, mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1, DUSP1) has emerged as a key molecule responsible for the repressive effects of steroi… Show more

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Cited by 17 publications
(21 citation statements)
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“…Importantly, it is controlled by p38 MAPK: its expression is p38 MAPK-dependent (28); and its mRNA destabilizing function is controlled by p38 MAPK/MK2-mediated phosphorylation on two key serine residues (S52 and S178) preventing the initiation of mRNA decay (29). We and others have underscored the importance of the MKP-1/p38/TTP regulatory network in the control of cytokine expression in vivo in MKP-1 and TTP transgenic mice (30,31) and in vitro (16,17,32,33). Thus, when we knockdown MKP-1 with siRNA, we cannot predict that we will observe an increase in cytokine production.…”
Section: Discussionmentioning
confidence: 94%
“…Importantly, it is controlled by p38 MAPK: its expression is p38 MAPK-dependent (28); and its mRNA destabilizing function is controlled by p38 MAPK/MK2-mediated phosphorylation on two key serine residues (S52 and S178) preventing the initiation of mRNA decay (29). We and others have underscored the importance of the MKP-1/p38/TTP regulatory network in the control of cytokine expression in vivo in MKP-1 and TTP transgenic mice (30,31) and in vitro (16,17,32,33). Thus, when we knockdown MKP-1 with siRNA, we cannot predict that we will observe an increase in cytokine production.…”
Section: Discussionmentioning
confidence: 94%
“…44,45 Corticosteroids are an attractive option due to their broad range of actions including anti-inflammatory and antiangiogenic effects. [46][47][48][49] Corticosteroid-loaded liposomes have been reported for several decades, but drug loading efficacy and release rates have presented significant challenges. The passive loading of hydrophilic corticosteroids in liposomes initially resulted in very low encapsulation efficiencies (<5%).…”
Section: Discussionmentioning
confidence: 99%
“…GCs [125] and a variety of other anti-inflammatory agonists have been reported to increase the expression of TTP. An emerging concept is that anti-inflammatory agonists may exert their effects not only by increasing TTP expression, but also by targeting DUSP1 to promote the activation of TTP [126]. Both Dusp1 −/− and Zfp36aa/aa mouse strains will be useful for further exploration of this concept.…”
Section: Therapeutic Implications Of the Regulation Of Ttp By Pp2a Anmentioning
confidence: 99%