Induction of cyclooxygenase-2 by heat shock protein 60  in macrophages and endothelial cells

Billack, Blasé; Heck, Diane E.; Mariano, Thomas M.; Gardner, Carol R.; Sur, Runa; Laskin, Debra L.; Laskin, Jeffrey D.

doi:10.1152/ajpcell.00609.2001

Cited by 42 publications

(31 citation statements)

References 67 publications

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“…Both ERK and JNK are required for Cox-2 promoter activity induced by IgE receptor aggregation in mast cells (74). ERK1/2 and p38 play a role in regulating HSP60-induced expression of Cox-2 in macrophages (74). Our results showed that of the three MAPKs, only p38, but not ERK and JNK, played a critical role in the CpG DNA-induced Cox-2 promoter activity (Fig.…”

Section: Discussionmentioning

confidence: 62%

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Myeloid Differentiation Factor 88-dependent Transcriptional Regulation of Cyclooxygenase-2 Expression by CpG DNA

Yeo¹,

Gravis

Yoon

et al. 2003

Journal of Biological Chemistry

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CpG DNA induces macrophage cyclooxgenase-2 (Cox-2) production. In this study, we have investigated a biochemical signaling pathway and transcription factors responsible for transcriptional regulation of the Cox-2 gene expression induced by CpG DNA. CpG DNAinduced Cox-2 promoter activity was completely inhibited by an endosomal acidification inhibitor (chloroquine), a TLR9 antagonist inhibitory CpG DNA, or overexpression of a dominant negative (DN) form of MyD88. In contrast, overexpression of DN-IRAK1 or DN-TRAF6 only partially inhibited CpG DNA-induced Cox-2 promoter activity and NF-B activation, indicating the presence of additional signaling modulators downstream of MyD88. CpG DNA-induced Cox-2 promoter activity was substantially suppressed in cells overexpressing super-suppressive IB (IB-arachidonic acid), DNp38, or DN-CREB. In addition, Cox-2 promoter-luciferase reporters with alterations in predicted cis-acting transcriptional regulatory elements revealed that C/EBP, Ets-1, NF-B, and CREB-binding sites are essential for optimal Cox-2 expression in response to CpG DNA. Conclusively, these results demonstrate that endosomal DNA processing and TLR9/MyD88-dependent activation of NF-B and p38 are required for transcriptional regulation of Cox-2 expression induced by CpG DNA, and suggest that interleukin-1 receptor-associated kinase and/or TRAF6 may be a diverging point for NF-B activation in response to CpG DNA in RAW264.7 cells.

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Section: Discussionmentioning

confidence: 62%

“…In contrast, LPS-induced murine Cox-2 promoter activity in RAW264.7 cells is dependent on ERK (43). Both ERK and JNK are required for Cox-2 promoter activity induced by IgE receptor aggregation in mast cells (74). ERK1/2 and p38 play a role in regulating HSP60-induced expression of Cox-2 in macrophages (74).…”

Section: Discussionmentioning

confidence: 99%

Myeloid Differentiation Factor 88-dependent Transcriptional Regulation of Cyclooxygenase-2 Expression by CpG DNA

Yeo¹,

Gravis

Yoon

et al. 2003

Journal of Biological Chemistry

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“…[44][45][46][47] HSP60 mediates its effects, in part, by binding to surface CD14 and Toll-like receptors, which are also utilized in LPS-mediated signaling and may, therein, serve as the endogenous ligand of the LPS receptor. [44][45][46][47][48] Taken together, these data suggest that HSP60 may be involved in pathologies involving inflammation.…”

Section: Nitric Oxidementioning

confidence: 99%

Macrophage Activation: Role of Toll-like Receptors, Nitric Oxide, and Nuclear Factor kappa B

Billack¹

2006

Am J Pharm Educ

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Macrophages play an important role in host-defense and inflammation. In response to an immune challenge, macrophages become activated and produce proinflammatory mediators that contribute to nonspecific immunity. The mediators released by activated macrophages include: superoxide anion; reactive nitrogen intermediates, such as nitric oxide and peroxynitrite; bioactive lipids; and cytokines. Although essential to the immune response, overproduction of certain macrophage-derived mediators during an immune challenge or inflammatory response can result in tissue injury and cellular death. The present report is focused on understanding some of the molecular mechanisms used by macrophages to produce reactive nitrogen intermediates in response to immunostimulatory agents such as heat shock protein 60 and bacterial lipopolysaccharide. The role of Toll-like receptors and transcription factors such as nuclear factor kappa B (NFkB) in the innate immune response is also described. A basic understanding of the underlying molecular mechanisms responsible for macrophage activation should serve as a foundation for novel drug development aimed at modulating macrophage activity.

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“…Sense and antisense primers for RT-PCR reactions of rat Sclc2a1 and Sclc2a4 and bovine Ptgs2 were synthesised according to published sequences [30][31][32] by Sigma-Aldrich (Rehovot, Israel). Synthesis of cDNA and PCR was carried out in a PTC-100 programmable thermal controller (MJ Research, Waltman, MA, USA) as described [29][30][31][32]. The nucleotide sequence of each PCR product was identical to the predicted sequences.…”

Section: Animalsmentioning

confidence: 99%

“…Bovine aortic endothelial cells (VEC) and smooth muscle cells (VSMC), which predominantly express SCLC2A1 (GLUT1) [30], were used to investigate the potential effects of COX2 (PTGS2) inhibitors on their hexose transport capacity. Fig.…”

Section: Cox2 (Ptgs2) Inhibitors Failed To Alter the Rate Of Hexose Tmentioning

confidence: 99%

Cyclooxygenase-2 (PTGS2) inhibitors augment the rate of hexose transport in L6 myotubes in an insulin- and AMPKα-independent manner

et al. 2006

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Aims/hypothesis: Some cyclooxygenase-2 (COX2, also known as prostaglandin-endoperoxide synthase 2 [PTGS2]) inhibitors have been shown to increase insulin sensitivity in man or induce hypoglycaemic episodes when overconsumed or taken in combination with oral hypoglycaemic drugs. These side-effects and their impact on patients are not always recognised in routine clinical practice. We investigated whether these side-effects of COX2 (PTGS2) inhibitors result from stimulation of the glucose transport system in skeletal muscle cells. Materials and methods: L6 myotube cultures were used to study effects of COX2 (PTGS2) inhibitors on the glucose transport system and their relationship to PTGS2 expression, insulin action and AMP-activated protein kinase α (AMPKα) activity. Results: The inhibitors niflumic acid, nimesulide and rofecoxib increased the rate of hexose uptake in L6 myotubes in the absence of insulin and in a dose-and time-dependent manner. They did this by increasing the total cell content of member 4 of the solute carrier family 2 (SCLC2A4, previously known as glucose transporter 4 [GLUT4]) (but not SCLC2A1 [previously known as GLUT1]) mRNA and protein and the amount of it in the plasma membrane. AMPKα was not involved in the latter effect since the inhibitors did not activate it. In addition, none of the inhibitors modulated the rate of hexose transport in vascular endothelial and smooth muscle cells expressing PTGS2 and SCLC2A1. Prostaglandin-endoperoxide synthase 1 (also known as cyclooxygenase 1) inhibitors (acetylsalicylic acid and indomethacin) did not alter the rate of hexose uptake and SCLC2A4 subcellular distribution in L6 myotubes. Conclusions/interpretation: This study suggests that certain COX2 (PTGS2) inhibitors can alter glucose homeostasis in vivo by stimulating glucose uptake in skeletal muscles that express PTGS2.

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Induction of cyclooxygenase-2 by heat shock protein 60 in macrophages and endothelial cells

Cited by 42 publications

References 67 publications

Myeloid Differentiation Factor 88-dependent Transcriptional Regulation of Cyclooxygenase-2 Expression by CpG DNA

Myeloid Differentiation Factor 88-dependent Transcriptional Regulation of Cyclooxygenase-2 Expression by CpG DNA

Macrophage Activation: Role of Toll-like Receptors, Nitric Oxide, and Nuclear Factor kappa B

Cyclooxygenase-2 (PTGS2) inhibitors augment the rate of hexose transport in L6 myotubes in an insulin- and AMPKα-independent manner

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