p38 kinase/cytosolic phospholipase A2/cyclooxygenase-2 pathway: A new signaling cascade for lipopolysaccharide-induced interleukin-1β and interleukin-6 release in differentiated U937 cells

Wang, Xiaohui; Xue, Hui; Xu, Qi; Zhang, Kai; Hao, Xiuhua; Wang, Luhuan; Yan, Guangtao

doi:10.1016/j.prostaglandins.2008.03.002

Cited by 17 publications

(11 citation statements)

References 30 publications

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“…Consistent with previous observations, 10 the expression of IL-6 at both mRNA and protein levels in mouse peritoneal macrophages was increased by LPS in a time-dependent manner (Figures 1a and b). The abundance of BLT2 mRNA was also markedly increased in these cells by LPS ( Figure 1a).…”

Section: Role Of Blt2 In Lps-induced Il-6 Synthesis In Macrophagessupporting

confidence: 93%

“…6 This TLR4-MyD88 pathway has been thought to have an important role in LPS-induced IL-6 synthesis. 7,8 Also, previous studies have shown that mice deficient in cytosolic phospholipase A 2 (cPLA 2 ) manifest reduced synthesis of IL-6 during experimental sepsis and that LPS-induced IL-6 production in macrophages is regulated through activation of cPLA 2 mediated by p38 mitogenactivated protein kinase (MAPK), 9,10 suggesting that cPLA 2 signaling also contributes to the LPS-induced production of IL-6 in macrophages. The downstream components of this cPLA 2 signaling pathway have remained unclear, however.…”

Section: Introductionmentioning

confidence: 99%

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MyD88–BLT2-dependent cascade contributes to LPS-induced interleukin-6 production in mouse macrophage

2015

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Endotoxic responses to bacterial lipopolysaccharide (LPS) are triggered by Toll-like receptor 4 (TLR4) and involve the production of inflammatory mediators, including interleukin-6 (IL-6), by macrophages. The detailed mechanism of IL-6 production by macrophages in response to LPS has remained unclear, however. We now show that LPS induces IL-6 synthesis in mouse peritoneal macrophages via the leukotriene B 4 receptor BLT2. Our results suggest that TLR4-MyD88 signaling functions upstream of BLT2 and that the generation of reactive oxygen species (ROS) by NADPH oxidase 1 (Nox1) and consequent activation of the transcription factor nuclear factor (NF)-κB function downstream of BLT2 in this response. These results suggest that a TLR4-MyD88-BLT2-Nox1-ROS-NF-κB pathway contributes to the synthesis of IL-6 in LPS-stimulated mouse macrophages.

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Section: Role Of Blt2 In Lps-induced Il-6 Synthesis In Macrophagessupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

MyD88–BLT2-dependent cascade contributes to LPS-induced interleukin-6 production in mouse macrophage

2015

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“…It is known that cPLA 2 can promote the release of pro-inflammatory cytokines (McGuirk et al, 2006;Wang et al, 2008). However, it is unlikely that the expression levels of cPLA 2 change through an NF-κB-mediated autocrine production of a pro-inflammatory cytokine such as TNF-α .…”

Section: Discussionmentioning

confidence: 99%

(S)-Tetrahydroisoquinoline Alkaloid Inhibits LPS-Induced Arachidonic Acid Release through Downregulation of cPLA2 Expression

Choi

Kim

et al. 2013

Molecules and Cells

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Sepsis, a systemic inflammatory response syndrome, remains a potentially lethal condition. (S)-1-α-Naphthylmethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (CKD712) is noted as a drug candidate for sepsis. Many studies have demonstrated its significant anti-inflammatory effects. Here we first examined whether CKD712 inhibits lipopolysaccharide (LPS)-induced arachidonic acid (AA) release in the RAW 264.7 mouse monocyte cell line, and subsequently, its inhibitory mechanisms. CKD712 reversed LPS-associated morphological changes in the RAW 264.7 cells, and inhibited LPS-induced release of AA in a concentrationdependent manner. The inhibition was apparently due to the diminished expression of a cytosolic form of phospholipase A 2 (cPLA 2 ) by CKD712, resulting from reduced NF-κB activation. Furthermore, CKD712 inhibited the activation of ERK1/2 and SAP/JNK, but not of p38 MAPK. CKD712 had no effect on the activity or phosphorylation of cPLA 2 and on calcium influx. Our results collectively suggest that CKD712 inhibits LPS-induced AA release through the inhibition of a MAPKs/NF-κB pathway leading to reduced cPLA 2 expression in RAW 264.7 cells.

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“…Activation of the ROS pathway is expected to be initiated by interactions with membrane lipids. These reactions generate free radicals and stimulate a cascade that may include other mediators often implicated in LPS-induced inflammation (14,17,27). The ROS-induced cascade appears to culminate in the decline in Hsp27 phosphorylation and increase in IKK␤-IB␣ phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide activates NF-κB by TLR4-Bcl10-dependent and independent pathways in colonic epithelial cells

Bhattacharyya¹,

Dudeja²,

Tobacman³

2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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p38 kinase/cytosolic phospholipase A2/cyclooxygenase-2 pathway: A new signaling cascade for lipopolysaccharide-induced interleukin-1β and interleukin-6 release in differentiated U937 cells

Cited by 17 publications

References 30 publications

MyD88–BLT2-dependent cascade contributes to LPS-induced interleukin-6 production in mouse macrophage

MyD88–BLT2-dependent cascade contributes to LPS-induced interleukin-6 production in mouse macrophage

(S)-Tetrahydroisoquinoline Alkaloid Inhibits LPS-Induced Arachidonic Acid Release through Downregulation of cPLA2 Expression

Lipopolysaccharide activates NF-κB by TLR4-Bcl10-dependent and independent pathways in colonic epithelial cells

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