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Biochemistry (Moscow)

, Volume 82, Issue 11, pp 1276–1284 | Cite as

Antiinflammatory effect of rosiglitazone via modulation of mRNA stability of interleukin 10 and cyclooxygenase 2 in astrocytes

  • E. V. Pankevich
  • A. A. Astakhova
  • D. V. ChistyakovEmail author
  • M. G. Sergeeva
Article

Abstract

Investigation of molecular mechanisms of proinflammatory stimuli signaling in astrocytes is important for understanding their role in pathogenesis of central nervous system diseases as well as in functioning of the innate immunity system in non-immune cells. Here we show that lipopolysaccharide (LPS) stimulation of primary rat astrocytes led to conventional inflammatory response: increase in both proinflammatory (tumor necrosis factor, TNFα; prostaglandin E2, PGE2) and antiinflammatory marker (interleukin 10, IL-10) levels. The protein level of cyclooxygenase 2 (COX-2) was also increased. Rosiglitazone strengthened LPS-induced mRNA expression of COX-2 and IL-10 but not TNFα. Rosiglitazone is an agonist of nuclear receptor PPARγ, but its impact on IL-10 expression was not influenced by a PPARγ antagonist, GW9662, suggesting PPARγ-independent effect of rosiglitazone. The degradation of mRNA is one of the steps of inflammation regulation and might be affected by small molecules. In experiments with actinomycin D, we found that mRNA half-lives of IL-10, COX-2, and TNFα in naive astrocytes were 70, 44, and 19 min, respectively. LPS stimulation caused 2-fold increase in IL-10 and COX-2 mRNA decay rates, whereas addition of rosiglitazone restored them to the initial level. TNFα decay rate was not changed by these stimulations. This suggests that mRNA decay rate could be regulated by small molecules. Moreover, rosiglitazone could be used as a substance stimulating the resolution of inflammation without influence on proinflammatory signals. These results open new perspectives in the search for inflammation resolution modulators.

Keywords

rosiglitazone inflammatory response astrocytes mRNA stability 

Abbreviations

CNS

central nervous system

COX-2

cyclooxygenase 2

IL-10

interleukin 10

LPS

lipopolysaccharide

PGE2

prostaglandin E2

TLR4

toll-like receptor 4

TNFα

tumor necrosis factor alpha

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Copyright information

© Pleiades Publishing, Ltd. 2017

Authors and Affiliations

  • E. V. Pankevich
    • 1
  • A. A. Astakhova
    • 2
  • D. V. Chistyakov
    • 2
    • 3
    Email author
  • M. G. Sergeeva
    • 2
  1. 1.Lomonosov Moscow State UniversityFaculty of Bioengineering and BioinformaticsMoscowRussia
  2. 2.Belozersky Institute of Physico-Chemical BiologyLomonosov Moscow State UniversityMoscowRussia
  3. 3.Pirogov Russian National Research Medical UniversityMoscowRussia

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