Lipopolysaccharide-induced release of arachidonic acid and prostaglandins in liver macrophages: Regulation by Group IV cytosolic phospholipase A2, but not by Group V and Group IIA secretory phospholipase A2

Dieter, Peter; Kolada, Angelika; Kamionka, Sabine; Schadow, Alexia; Kaszkin, Marietta

doi:10.1016/s0898-6568(01)00243-1

Cited by 55 publications

(40 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TNF-a, produced in response to LPS, activates cPLA 2 (31), explaining the cytokine's ability to inhibit CRIg expression. Consistent with this concept, LPS and TNF-a, which depress CRIg expression but upregulate CR3 expression in macrophages, promote the expression and activation of cPLA 2 (31)(32)(33). The signaling loop involving cPLA 2 , arachidonate, and PKCa also promotes CR3 expression.…”

Section: Discussionmentioning

confidence: 63%

Protein Kinase Cα Regulates the Expression of Complement Receptor Ig in Human Monocyte–Derived Macrophages

Usuwanthim

Munawara

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

The complement receptor Ig (CRIg) is selectively expressed by macrophages. This receptor not only promotes the rapid phagocytosis of bacteria by macrophages but also has anti-inflammatory and immunosuppressive functions. Previous findings have suggested that protein kinase C (PKC) may be involved in the regulation of CRIg expression in human macrophages. We have now examined the role of PKCα in CRIg expression in human monocyte-derived macrophages (MDM). Macrophages nucleofected with plasmid containing short hairpin RNA against PKCα showed markedly reduced expression of PKCα, but normal PKCζ expression, by Western blotting analysis, and vice versa. PKCα-deficient MDM showed increased expression of CRIg mRNA and protein (both the long and short form), an increase in phagocytosis of complement-opsonized Candida albicans, and decreased production of TNF-α and IL-6. TNF-α caused a marked decrease in CRIg expression, and addition of anti-TNF mAb to the TNF-α–producing MDMs increased CRIg expression. PKCα-deficient macrophages also showed significantly less bacterial LPS-induced downregulation of CRIg. In contrast, cells deficient in PKCα showed decreased expression of CR type 3 (CR3) and decreased production of TNF-α and IL-6 in response to LPS. MDM developed under conditions that increased expression of CRIg over CR3 showed significantly reduced production of TNF-α in response to opsonized C. albicans. The findings indicate that PKCα promotes the downregulation of CRIg and upregulation of CR3 expression and TNF-α and IL-6 production, a mechanism that may promote inflammation.

show abstract

Section: Discussionmentioning

confidence: 63%

Protein Kinase Cα Regulates the Expression of Complement Receptor Ig in Human Monocyte–Derived Macrophages

Usuwanthim

Munawara

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…cPLA 2 is the only known PLA 2 activated by receptor-mediated events (50). A wide variety of extracellular stimuli have been found to induce activation or increase synthesis of cPLA 2 in diverse cell models (34,51,52). However, in LPS-induced inflammation, the phagocyte receptor and pathway required for cPLA 2 activation leading to pro-inflammatory lipid production remain to be defined.…”

Section: Discussionmentioning

confidence: 99%

Toll-like Receptor 4 Signaling Regulates Cytosolic Phospholipase A2 Activation and Lipid Generation in Lipopolysaccharide-stimulated Macrophages

Shelhamer

2005

Journal of Biological Chemistry

110

View full text Add to dashboard Cite

Inflammatory lipid mediators such as prostaglandins and leukotrienes play crucial roles in the pathogenesis of bacterial lipopolysaccharide (LPS)-induced inflammation. Cytosolic phospholipase A 2 (cPLA 2 ) is a key enzyme in the generation of pro-inflammatory lipid mediators. Here, we found that Toll-like receptor 4 (TLR4) is essential for LPS-induced cPLA 2 activation and lipid release. Inhibition of TLR4 protein expression by TLR4 small interfering RNA or neutralization of TLR4 by the specific antibody against TLR4/MD2 blocked cPLA 2 phosphorylation and cPLA 2 -hydrolyzed arachidonic acid release. Furthermore, activation of the TLR4 signaling pathway by LPS regulated cPLA 2 activation and lipid release. cPLA 2 phosphorylation and cPLA 2 -hydrolyzed lipid release were significantly impaired when TLR4 adaptor protein, either MyD88 or TRIF, was knocked down in LPS-stimulated macrophages. Similarly, LPS-induced arachidonate release was inhibited in cells transfected with a dominant-negative MyD88 or TRIF construct. Subsequently, cPLA 2 activation could be suppressed by inhibition of the TLR4 adaptor protein-directed p38 and ERK MAPK pathways. These findings suggest that, in LPS-induced inflammation, the TLR4-mediated MyD88-and TRIF-dependent MAPK pathways result in cPLA 2 activation and production of pro-inflammatory lipid mediators.

show abstract

“…LPS acts on inflammatory cells to enhance generation of arachidonic acid (44,45) and its metabolites (16), as well as to increase the formation of NO (17). LPS exposure also induces the release of various cytokines/growth factors, such as IL-1, IL-6, IL-8, TNF-␣ (46 -48).…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide Down-Regulates the Leukotriene C4 Synthase Gene in the Monocyte-Like Cell Line, THP-1

Serio

Johns

Luo

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

We studied the effects of LPS on cysteinyl leukotriene (LT) synthesis and LTC4 synthase expression in mononuclear phagocytes. Conditioning of the monocyte-like cell line, THP-1, with LPS for 7 days resulted in significantly decreased ionophore-stimulated LTC4 release. The putative LPS receptor, Toll-like receptor 4, was expressed in THP-1 cells. LPS down-regulated LTC4 synthase mRNA in THP-1 cells in a dose- and time-dependent manner, with down-regulation observed as early as 4 h. Conditioning of actinomycin D-treated cells with LPS resulted in no change in the rate of LTC4 synthase mRNA decay. LPS treatment of THP-1 cells, transiently transfected with a LTC4 synthase promoter (1.35 kb)-reporter construct, decreased promoter activity. Neutralization of TNF-α and inhibition of mitogen-activated protein kinase kinase/extracellular signal-regulated kinase did not inhibit the effect of LPS. Treatment of cells with a Toll-like receptor 4-blocking Ab and an inhibitor of NF-κB activation resulted in inhibition of the LPS effect, while activation of NF-κB and p50/p65 overexpression down-regulated the LTC4 synthase gene. LPS down-regulates cysteinyl LT release and LTC4 synthase gene expression in mononuclear phagocytes by an NF-κB-mediated mechanism.

show abstract

Lipopolysaccharide-induced release of arachidonic acid and prostaglandins in liver macrophages: Regulation by Group IV cytosolic phospholipase A2, but not by Group V and Group IIA secretory phospholipase A2

Cited by 55 publications

References 20 publications

Protein Kinase Cα Regulates the Expression of Complement Receptor Ig in Human Monocyte–Derived Macrophages

Protein Kinase Cα Regulates the Expression of Complement Receptor Ig in Human Monocyte–Derived Macrophages

Toll-like Receptor 4 Signaling Regulates Cytosolic Phospholipase A2 Activation and Lipid Generation in Lipopolysaccharide-stimulated Macrophages

Lipopolysaccharide Down-Regulates the Leukotriene C4 Synthase Gene in the Monocyte-Like Cell Line, THP-1

Contact Info

Product

Resources

About