Role of JNK and NF-κB pathways in Porphyromonas gingivalis LPS-induced vascular cell adhesion molecule-1 expression in human aortic endothelial cells

Abstract

An increasing number of studies have shown a correlation between Porphyromonas gingivalis (P. gingivalis) infection and atherosclerosis. A recent study demonstrated that the expression of vascular cell adhesion molecule-1 (VCAM-1) was induced by P. gingivalis lipopolysaccharide (LPS) in human aortic endothelial cells (HAECs). The activation of p38 mitogen-activated protein kinase (p38 MAPK) was at least partially involved in this process. Those results suggested the potential involvement of P. gingivalis LPS in the pathogenesis of atherosclerosis. However, the mechanism involved in P. gingivalis LPS-induced VCAM-1 production has not yet been elucidated. The present study examined the role of the c-Jun N-terminal kinase (JNK) and nuclear factor‑κB (NF‑κB) cell signaling pathways in P. gingivalis LPS-induced VCAM-1 expression in HAECs. Western blotting was used to investigate the activation of JNK and NF‑κB pathways in HAECs exposed to P. gingivalis LPS. Following this, specific pharmacological inhibitors were introduced and the protein production of VCAM-1 was studied. The results showed that the JNK and NF‑κB pathways in HAECs were capable of being activated by P. gingivalis LPS. The inhibition of NF-κB by SN50 significantly attenuated P. gingivalis LPS-induced VCAM-1 expression, while the inhibition of JNK by SP600125 enhanced VCAM-1 expression in P. gingivalis LPS-treated HAECs. Therefore, the results indicated that NF‑κB was essential for the P. gingivalis LPS-induced VCAM-1 expression in HAECs and that JNK may be a suppressor of VCAM-1 expression in HAECs.

EOLA1 Inhibits Lipopolysaccharide-Induced Vascular Cell Adhesion Molecule-1 Expression by Association with MT2A in ECV304 Cells

“…LPS has been shown to initiate TLR4 mediated intracellular signaling events, including the activation of NF- κ B, which ultimately leads to the transcription and release of VCAM-1 in endothelial cells to attract mononuclear macrophage accumulation for inflammatory response [ 15 , 16 ]. Recent study also showed that LPS-induced VCAM-1 expression contributes to the initiation of the atherosclerotic process [ 17 , 18 ]. Our experiments showed that LPS induces EOLA1 expression along with VCAM-1 induction, overexpression of EOLA1 reduces the LPS-induced production of VCAM-1 in ECV304 cells, and depletion of EOLA1 significantly enhances the LPS-induced production of VCAM-1.…”

Salmeterol, a Long‐Acting β2‐Adrenergic Receptor Agonist, Inhibits Macrophage Activation by Lipopolysaccharide From Porphyromonas gingivalis

“…Previous work of the authors using E. coli LPS on primary microglia‐enriched cultures has shown that salmeterol, and other long‐acting β2‐AR agonists, exert a strong anti‐inflammatory effect on microglia when used at concentrations of 10 −8 to 10 −10 M by inhibiting activation of two key proinflammatory signaling pathways, the NF‐κB pathway and the MAPK pathway 30 . It is well known that MAPKs and NF‐κB are involved in Pg LPS‐induced cytokine expression, 46 , 47 so it seemed logical that salmeterol would mediate its anti‐inflammatory effect on murine and human macrophages via the same basic cellular mechanism. It has been well documented that production of proinflammatory cytokines and NO is primarily regulated at the transcriptional level, and expression of genes, including TNF‐α , IL‐1β , IL‐6 , IL‐8 , and iNOS , in macrophages and microglial cells is strongly regulated by the NF‐κB classic pathway 48 .…”

Porphyromonas�gingivalis induced inflammatory responses and promoted apoptosis in lung epithelial cells infected with H1N1 via the Bcl‑2/Bax/Caspase‑3 signaling pathway

“…In the process of periodontal epithelial tissue and bone tissue destruction, P. gingivalis serves an important role; it secretes a large number of toxic factors to stimulate the host cells into producing the inflammatory cytokines interleukin (IL)-1, IL-6 and tumor necrosis factor-α (TNF-α), which lead to physiological and pathological damage ( 14 ). Influenza A virus (IAV) H1N1 is a lethal pathogen that infects humans and animals.…”