The synthetic triterpenoid, CDDO-Me, modulates the proinflammatory response to in vivo lipopolysaccharide challenge.

Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research
Jeffery J AulettaJohn J Letterio

Abstract

The synthetic triterpenoid, CDDO-Me, has potent antiproliferative and antioxidant properties. However, its immunomodulatory effects in the context of LPS challenge are incompletely defined. Pretreatment with oral CDDO-Me significantly improved survival following lethal-dose LPS challenge in mice. To define this protection further, we measured effects of CDDO-Me pretreatment on splenocyte populations and cytokine production following LPS challenge, using low-level LPS pretreatment as an in vivo control for reducing cytokine production. Despite similar decreases in levels of LPS-inducible, circulating proinflammatory cytokines (IL-12p70, IFN-gamma, IL-6, IL-17, and IL-23) and increases in heme oxygenase 1 (HO-1) protein expression, low-dose LPS and CDDO-Me pretreatments markedly differed in their overall response profiles. Splenocytes from LPS-pretreated mice contained reduced numbers of dendritic cells, increased percentages of Th17 and T-regulatory cells, lower levels of TLR-inducible IL-6, and higher levels of TLR-inducible IL-10. In contrast, CDDO-Me protection against LPS challenge had no impact on absolute numbers or distribution of splenocyte subsets, despite attenuating in vivo induction of proinflammatory cytokines in an...Continue Reading

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Citations

Feb 22, 2012·Journal of Natural Products·Tonibelle N Gatbonton-SchwagerGregory P Tochtrop
Aug 4, 2012·Journal of the American Society of Nephrology : JASN·Scott A ReismanColin J Meyer
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Jul 25, 2014·The Journal of Toxicological Sciences·Mika KitsukawaYohei Miyamoto
Oct 30, 2020·International Journal of Molecular Sciences·Andrey V MarkovEvgeniya B Logashenko

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Methods Mentioned

BETA
dissection
FACS
flow cytometry
ELISA
bronchoalveolar lavages

Software Mentioned

ImageJ

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