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Suppression of cyclooxygenase-2 expression induced by Toll-like receptor 2 or 4 agonists by (E)-isopropyl 4-oxo-4-(2-oxopyrrolidin-1-yl)-2-butenoate

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Abstract

Inflammation can be initiated by invading microbial pathogens. Toll-like receptors (TLRs) recognize molecular structures derived from microbial pathogens and regulate the activation of innate immunity. TLR signaling pathways trigger the activation of nuclear factor-κB(NF-κB) transcription factor, leading to the induction of inflammatory gene products such as cyclooxygenase-2. Here, we present biochemical evidence that the fumaryl pyrrolidinone, (E)-isopropyl 4-oxo-4-(2-oxopyrrolidin-1-yl)-2-butenoate (IPOP), previously synthesized in our laboratory inhibits NF-κB activation induced by TLR agonists and overexpression of two downstream signaling components of TLRs. IPOP also inhibits TLR agonist-induced expression of cyclooxygenase-2. Our results suggest that IPOP can modulate TLR-mediated inflammatory responses and, potentially, the risk of many chronic inflammatory diseases.

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Authors and Affiliations

  1. Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan-Si, Chungnam, 336-745, Korea

    A-Neum Lee & Hyung-Sun Youn

  2. Departments of Medical Science, College of Medical Sciences, Soonchunhyang University, Asan-Si, Chungnam, 336-745, Korea

    Se-Jeong Park & Hyung-Sun Youn

  3. Department of Chemistry, College of Natural Sciences, Soonchunhyang University, Asan-Si, Chungnam, 336-745, Korea

    Kwang Oh Koh & Dae Young Kim

Authors
  1. A-Neum Lee
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  2. Se-Jeong Park
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  3. Kwang Oh Koh
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  4. Dae Young Kim
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  5. Hyung-Sun Youn
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Correspondence to Hyung-Sun Youn.

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Lee, AN., Park, SJ., Koh, K.O. et al. Suppression of cyclooxygenase-2 expression induced by Toll-like receptor 2 or 4 agonists by (E)-isopropyl 4-oxo-4-(2-oxopyrrolidin-1-yl)-2-butenoate. Mol. Cell. Toxicol. 7, 39–44 (2011). https://doi.org/10.1007/s13273-011-0006-0

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  • DOI: https://doi.org/10.1007/s13273-011-0006-0

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