Lipopolysaccharide-Induced Nitric Oxide and Prostaglandin E2 Production Is Inhibited by Tellimagrandin II in Mouse and Human Macrophages

  • Life (Basel). 2021 Apr 30;11(5):411. doi: 10.3390/life11050411.
Chun-Yu Lin  1  2  3  4 ,  Shih-Han Kao  2 ,  Ling-Chien Hung  2 ,  Hsin-Ju Chien  1 ,  Wen-Hung Wang  1  2 ,  Yu-Wei Chang  2 ,  Yen-Hsu Chen  1  2  5
Affiliations
  • 1. Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
  • 2. School of Medicine, Graduate Institute of Medicine, College of Medicine, Center for Tropical Medicine and Infectious Diseases Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
  • 3. Department of Surgical Sciences, Uppsala University, 751 23 Uppsala, Sweden.
  • 4. Department of Medical Biochemistry and Microbiology, Uppsala University, 751 23 Uppsala, Sweden.
  • 5. Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, Hsinchu 300, Taiwan.
PMID: 33946374 DOI: 10.3390/life11050411
Abstract

Sepsis develops from a serious microbial Infection that causes the immune system to go into overdrive. The major Microorganisms that induce sepsis are Gram-negative bacteria with lipopolysaccharide (LPS) in their cell walls. Nitric oxide (NO) and cyclooxygenase-2 (COX-2) are the key factors involved in the LPS-induced pro-inflammatory process. This study aimed to evaluate the effects of polyphenol Tellimagrandin II (TGII) on anti-inflammatory activity and its underlying basic mechanism in murine macrophage cell line RAW 264.7 and human monocyte-derived macrophages. Macrophages with more than 90% cell viability were found in the cytotoxicity assay under 50 μM TGII. Pre- or post-treatment with TGII significantly reduced LPS-induced inducible nitric oxide synthase (NOS2) protein and mRNA expression, reducing LPS-induced COX-2 protein. Downstream of NOS2 and COX-2, NO and prostaglandin E2 (PGE2) were significantly inhibited by TGII. Upstream of NOS2 and COX-2, phospho-p65, c-Fos and phospho-c-jun were also reduced after pre-treatment with TGII. Mitogen-activated protein kinases (MAPKs) are also critical to nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) stimulation, and phospho-p38 expression was found to have been blocked by TGII. TGII efficiently reduces LPS-induced NO production and its upstream regulatory factors, suggesting that TGII may be a potential therapeutic agent for sepsis and Other inflammatory diseases.

Keywords
Tellimagrandin II; cyclooxygenase-2; inflammation; macrophage; nitric oxide.
Products