Resveratrol Inhibits Inflammation Induced by Heat-Killed Listeria monocytogenes

Abstract

Resveratrol is a polyphenolic compound in red wine that has antioxidant and cardioprotective effects in animal models. Listeria monocytogenes is a pathogen that mainly affects immunocompromised individuals and is initially detected at the cell surface or in phagosomes by toll-like receptor 2. Many antioxidants also exert anti-inflammatory activities; therefore, we evaluated the anti-inflammatory properties of resveratrol by studying the various inflammatory responses induced by heatkilled L. monocytogenes (HKLM). Resveratrol strongly blocked HKLM-induced NADPH oxidase-1 mRNA and reactive oxygen species production by macrophages. Resveratrol also suppressed monocyte chemotactic protein-1 expression, cyclooxygenase-2 expression, prostaglandin production, inducible nitric oxide (NO) synthase expression, and NO production induced by HKLM. We investigated the signaling pathway involved in the resveratrol effect. HKLM stimulated glycogen synthase kinase 3b (GSK3b) and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. The involvement of GSK3b and ERK1/2 was tested using inhibitors. While the GSK3b inhibitor LiCl potentiated the effect of HKLM, the MEK inhibitor U0126 blocked these responses. Additionally, pretreatment with resveratrol blocked phosphorylation of both kinases induced by HKLM. These results suggest that HKLM is strong inducer of inflammatory mediators, and that the inhibitory effect of resveratrol may be mediated by the GSK3b and ERK1/2 pathways.KEY WORDS: COX-2 HKLM iNOS MCP-1 NADPH oxidase 1 resveratrol

Role of JAK2–STAT3 in TLR2‐mediated tissue factor expression

“…TF expression has also been reported to be regulated by cooperation of the phosphatidylinositol 3-kinase (PI3 kinase) and MAP kinase pathway in endothelial cells [Guha and Mackman, 2002]. Specifically, TLR2 stimulation causes JAK2 phosphorylation, which leads to ERK1/2 phosphorylation [Park et al, 2012a]. Therefore, our finding of JAK2 involvement in TF expression is of great importance.…”

“…We recently reported the correlation of JAK and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in TLR signaling. Specifically, TLR2 stimulation causes JAK2 phosphorylation, which leads to ERK1/2 phosphorylation [Park et al, 2012a]. This signaling mechanism is a very unique, unexpected reaction.…”

Small molecule SIRT1 activators for the treatment of aging and age-related diseases

“…This has led to considerable excitement about the use of STACs for the treatment of inflammatory and autoimmune disorders [36]. Resveratrol reduces levels of inflammatory cytokines in LPS-stimulated macrophages [62] and peripheral blood mononuclear cells [63], protects cartilage against experimentally-induced inflammatory arthritis in rabbits [64], and inhibits inflammation caused by Listeria monocytogenes , a pathogen that typically affects immuno-compromised individuals [65]. Other mouse models of tissue inflammation have also responded well to resveratrol, including chronic obstructive pulmonary disease (COPD) [66], and Crohn’s disease [67].…”

Investigation of Possible Immunomodulatory Effects of Resveratrol as an Add-on Therapy in a Murine Model of Ovalbumin-Induced Bronchial Asthma

“…Park et al investigated the effects of resveratrol on inflammatory mediator production induced by Heat-Killed Listeria monocytogenes (HKLM), a TLR2 agonist. Resveratrol showed anti-inflammatory effects by inhibiting HKLM-induced Nox-1 expression, ROS production, monocyte chemotactic protein-1 expression (MCP-1 expression), cyclooxygenase-2 (COX-2) expression, metabolite (PGE2 and PGI2) production, and nitric oxide (NO) production after inducible nitric oxide (iNOS) expression [26]. The potent antioxidant and anti-inflammatory properties of resveratrol were linked to inhibition of cytokine stimulated inducible nitric oxide synthase expression and nitrite production, inhibition of granulocytemacrophage colony stimulating factor release(GM-CSF), IL-8 release, and cyclooxygenase-2 expression [27].…”