Orostachys japonicus Inhibits Expression of the TLR4, NOD2, iNOS, and COX-2 Genes in LPS-Stimulated Human PMA-Differentiated THP-1 Cells by Inhibiting NF-κB and MAPK Activation.

Yeo-Kwang Yoon,Hong-Jung Woo,Youngchul Kim

doi:10.1155/2015/682019

Abstract

Orostachys japonicus is traditionally used as an inflammatory agent. In this report, we investigated the effects of O. japonicus extract on the expression of genes encoding pathogen-recognition receptors (TLR2, TLR4, NOD1, and NOD2) and proinflammatory factors (iNOS, COX-2, and cytokines) in LPS-stimulated PMA-differentiated THP-1 cells and the NF-κB and MAPK pathways. O. japonicus induced toxicity at high concentrations but had no effect at concentrations lower than 25 μg/mL. O. japonicus inhibited LPS-induced TLR4 and NOD2 mRNA levels, suppressed LPS-induced iNOS and COX-2 transcription and translocation, and downregulated LPS-induced proinflammatory cytokine (IL-1β, IL-6, IL-8, and TNF-α) mRNA levels. In addition, O. japonicus inhibited LPS-induced NF-κB activation and IκBα degradation and suppressed LPS-induced JNK, p38 MAPK, and ERK phosphorylation. Overall, our results demonstrate that the anti-inflammatory effects of O. japonicus are mediated by suppression of NF-κB and MAPK signaling, resulting in reduced TLR4, NOD2, iNOS, and COX-2 expression and inhibition of inflammatory cytokine expression.

Highlights

Orostachys japonicus (O. japonicus) is traditionally used as an inflammatory agent, antifebrile, homeostatic agent, and antidote and anticancer agent [1]
We investigated the effects of O. japonicus on the expression of genes encoding pathogen-recognition receptors (TLR2, TLR4, NOD1, and NOD2) and proinflammatory factors in LPS-stimulated PMA-differentiated THP-1 cells, as well as the nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) pathways
We investigated the effect of O. japonicus on the expression of TLR2, TLR4, NOD1, and NOD2 in THP-1 cells. mRNA levels were analyzed using real-time PCR

Summary

Introduction

Orostachys japonicus (O. japonicus) is traditionally used as an inflammatory agent, antifebrile, homeostatic agent, and antidote and anticancer agent [1]. Humans have various pathogen-recognition receptors including TLRs, nucleotidebinding oligomerization domain- (NOD-) like receptors (NLRs), and retinoic acid-inducible gene-1- (RIG-1-) like receptors [5,6,7]. These receptors transduce signals to activate nuclear factor-κB (NF-κB), which subsequently drives the induction of several proinflammatory cytokines and chemokines [8,9,10]. TLR2 is involved in the recognition of a broad range of microbial products, and TLR4 is the signal-transducing receptor for LPS [11]. NOD1 recognizes mainly Gram-negative bacteria, whereas NOD2 recognizes most Gram-positive and Gram-negative bacteria [13]

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Conclusion