PGE2 enhances cytokine-elicited nitric oxide production in mouse cortical collecting duct cells

Huang, Chien‐Ning; Liu, Kaili; Cheng, Chun-Hsu; Lin, Yu‐Sheng; Lin, Min-Jon; Lin, Ting‐Hui

doi:10.1016/j.niox.2005.01.004

Cited by 9 publications

(7 citation statements)

References 42 publications

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“…This finding is also in accordance with a series of our previous reports of defective NO and cGMP production in mPGES-1 null mice after highsalt loading or DOCA-salt treatment (22,24). Other investigations also suggest the potential of PGE 2 in stimulating NO and cGMP production in various renal or extrarenal systems (16,17,26,40). Overall, these results support the existence of PGE 2 /NO/cGMP pathway that appears to be important in renal salt handling.…”

Section: Discussionsupporting

confidence: 91%

mPGES-1-derived PGE₂ mediates dehydration natriuresis

Liu

Sun

Kakizoe

et al. 2013

American Journal of Physiology-Renal Physiology

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is a natriuretic factor whose production is elevated after water deprivation (WD) but its role in dehydration natriuresis is not well-defined. The goal of the present study was to investigate the role of microsomal prostaglandin E synthase-1 (mPGES-1) in dehydration natriuresis. After 24-h WD, wild-type (WT) mice exhibited a significant increase in 24-h urinary Na ϩ excretion accompanied with normal plasma Na ϩ concentration and osmolality. In contrast, WD-induced elevation of urinary Na ϩ excretion was completely abolished in mPGES-1 knockout (KO) mice in parallel with increased plasma Na ϩ concentration and a trend increase in plasma osmolality. WD induced a 1.8-fold increase in urinary PGE2 output and a 1.6-fold increase in PGE2 content in the renal medulla of WT mice, both of which were completely abolished by mPGES-1 deletion. Similar patterns of changes were observed for urinary nitrate/nitrite and cGMP. The natriuresis in dehydrated WT mice was associated with a significant downregulation of renal medullary epithelial Na channel-␣ mRNA and protein, contrasting to unaltered expressions in dehydrated KO mice. By quantitative RT-PCR, WD increased the endothelial nitric oxide synthase (eNOS), inducible NOS, and neuronal NOS expressions in the renal medulla of WT mice by 3.9-, 1.48-, and 2.6-fold, respectively, all of which were significantly blocked in mPGES-1 KO mice. The regulation of eNOS expression was further confirmed by immunoblotting. Taken together, our results suggest that mPGES-1-derived PGE2 contributes to dehydration natriuresis likely via NO/ cGMP. mPGES-1; PGE2; dehydration natriuresis; cGMP; nitric oxide DEHYDRATION LEADS TO THE DEPLETION of plasma volume and the increase of body fluid osmolality. Such changes trigger the homeostatic response to conserve the fluids through the thirst mechanism, vasopressin release, and potentiated renal reabsorption. During the early stage of dehydration, an important physiological response is an acute increase in urinary Na ϩ excretion, a phenomenon termed dehydration natriuresis. This response will help prevent the further rise of plasma Na ϩ concentration and extracellular tonicity. Dehydration natriuresis has been demonstrated in humans as well as in other mammalian species, including dog, sheep, rat, and mouse (1,7,18,28,31,33,36,37). A number of factors such as neurohypophysial hormones and serum-and glucocorticoid-inducible kinase (Sgk1) are implicated in mediating dehydration natriuresis but the precise mechanism remains unclear.PGE 2 is a major prostanoid in the kidney and possesses natriuretic property owing to its ability to inhibit Na ϩ transport in the distal nephron (3, 6, 39, 43). The elevation of urinary PGE 2 in response to dehydration accompanied with increased renal medullary cyclooxygenase (COX)-2 expression has also been well-demonstrated (29,41,47). However, the functional implication of dehydration-induced renal PGE 2 synthesis is still incompletely understood.To date, three PGE synthases (PGES) have been cloned, including microsomal PGE...

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Section: Discussionsupporting

confidence: 91%

mPGES-1-derived PGE₂ mediates dehydration natriuresis

Liu

Sun

Kakizoe

et al. 2013

American Journal of Physiology-Renal Physiology

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“…Further, studies have reported that PGE2 triggers the Th1 response by the enhanced production of IL-2 and IFN-␥, which culminated in higher IL-12 production in dendritic cells [63,64]. In addition, PGE2 is suggested to enhance NO production in various cell types including rat liver macrophages known as Kupffer cells, mouse cortical-collecting duct cells, or rat gastric mucosa or to up-regulate astrocytic iNOS expression under the proinflammatory environment [65][66][67][68][69]. These findings have suggested that PGE2 could act in a positive-feedback loop in triggering NO production, which in turn, modulates signaling cascades leading to regulation of critical cell-fate decisions associated with inflammation during hostmycobacteria interactions.…”

Section: Discussionmentioning

confidence: 99%

M. bovisBCG induced expression of COX-2 involves nitric oxide-dependent and -independent signaling pathways

Bansal

Narayana

Patil

et al. 2009

Journal of Leukocyte Biology

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In a multifaceted immunity to mycobacterial infection, induced expression of cyclooxygenase-2 (COX-2) by Mycobacterium bovis bacillus Calmette-Guerin (BCG) may act as an important influencing factor for the effective host immunity. We here demonstrate that M. bovis BCG-triggered TLR2-dependent signaling leads to COX-2 and PGE2 expression in vitro in macrophages and in vivo in mice. Further, the presence of PGE2 could be demonstrated in sera or cerebrospinal fluid of tuberculosis patients. The induced COX-2 expression in macrophages is dependent on NF-kappaB activation, which is mediated by inducible NO synthase (iNOS)/NO-dependent participation of the members of Notch1-PI-3K signaling cascades as well as iNOS-independent activation of ERK1/2 and p38 MAPKs. Inhibition of iNOS activity abrogated the M. bovis BCG ability to trigger the generation of Notch1 intracellular domain (NICD), a marker for Notch1 signaling activation, as well as activation of the PI-3K signaling cascade. On the contrary, treatment of macrophages with 3-morpholinosydnonimine, a NO donor, resulted in a rapid increase in generation of NICD, activation of PI-3K pathway, as well as the expression of COX-2. Stable expression of NICD in RAW 264.7 macrophages resulted in augmented expression of COX-2. Further, signaling perturbations suggested the involvement of the cross-talk of Notch1 with members with the PI-3K signaling cascade. These results implicate the dichotomous nature of TLR2 signaling during M. bovis BCG-triggered expression of COX-2. In this perspective, we propose the involvement of iNOS/NO as one of the obligatory, early, proximal signaling events during M. bovis BCG-induced COX-2 expression in macrophages.

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“…16,18 EP2 has also been localized to mouse CCD cells, 14 the rabbit CCD, 33 and the human connecting tubule, 20 but kidney EP2 localization in mouse, rabbit, and human CDs is not consistently found. 13,14,21,22,33 EP2 is also expressed in renomedullary interstitial cells. 33 EP2 couples to Gs and signals through the second messenger cAMP.…”

Section: Postobstructive Polyuriamentioning

confidence: 99%

“…Butaprost increased ser-256 phosphorylation of AQP2 in cortical tubule suspensions and increased apical membrane accumulation of AQP2 in rat kidney slices, 18 indicating that EP2 is expressed in the CD, which has previously been an issue of some debate. 13,14,16,[18][19][20][21][22][23] This notion was further strengthened by the finding that butaprost was able to decrease polyuria in a rat model of x-linked NDI. Together, EP2 and EP4 are potential candidates for mediating urinary concentration in conditions with absent V2R signaling, but whether they can act alongside VP to increase urine concentration remains unknown.…”

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confidence: 96%

Is There a Role for PGE2 in Urinary Concentration?

Olesen

Fenton

2013

Journal of the American Society of Nephrology

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Prostanoids are prominent, yet complex, components in the maintenance of body water homeostasis. Recent functional and molecular studies have revealed that the local lipid mediator PGE2 is involved both in water excretion and absorption. The biologic actions of PGE2 are exerted through four different G-protein-coupled receptors; designated EP1-4, which couple to separate intracellular signaling pathways. Here, we discuss new developments in our understanding of the actions of PGE2 that have been uncovered utilizing receptor specific agonists and antagonists, EP receptor and PG synthase knockout mice, polyuric animal models, and the new understanding of the molecular regulation of collecting duct water permeability. The role of PGE2 in urinary concentration comprises a variety of mechanisms, which are not fully understood and likely depend on which receptor is activated under a particular physiologic condition. EP3 and microsomal PG synthase type 1 play a role in decreasing collecting duct water permeability and increasing water excretion, whereas EP2 and EP4 can bypass vasopressin signaling and increase water reabsorption through two different intracellular signaling pathways. PGE2 has an intricate role in urinary concentration, and we now suggest how targeting specific prostanoid receptor signaling pathways could be exploited for the treatment of disorders in water balance. The neurohypophyseal hormone, vasopressin (VP), is a major regulator of renal water excretion, predominantly through the seven trans-membrane receptor (7TMR) V2R. It binds to Gas, inducing the cAMP second messenger system, resulting in increased NaCl absorption by the thick ascending limb and increased urea transport in the inner medullary collecting ducts (IMCDs). [1][2][3] In addition, VP induces accumulation of the water channel aquaporin-2 (AQP2) in the rate-limiting apical plasma membrane of collecting duct (CD) principal cells, 4 a process that involves a diverse range of post-translational modifications including phosphorylation of AQP2. 5 Thus, VP increases the osmotic gradient for water transport and the water permeability (Pf) of the CD simultaneously.In addition to systemic hormones, local regulatory factors play a role in the CD, of which PGE2 (Figure 1) is the focus of this review. 6-9 PGE2 has a diverse range of biologic actions elicited by four different 7TMRs. The renal localization of EP receptors and intracellular signaling pathways are diverse (Table 1). Here, we propose that urinary concentration does not rely exclusively on fluctuations in plasma VP concentrations, but that the locally derived lipid mediator, PGE2, plays an important role in regulating water excretion. PGE2 IN THE MODULATION OF URINARY CONCENTRATING MECHANISMSThe ability of PGE2 to modulate the effects of VP in the CD has been described in a range of experimental studies and discussed in previous reviews. [36][37][38][39] The present focus is on understanding the mechanisms for this effect, and on recent in vivo studies elucidating the role of P...

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PGE2 enhances cytokine-elicited nitric oxide production in mouse cortical collecting duct cells

Cited by 9 publications

References 42 publications

mPGES-1-derived PGE₂ mediates dehydration natriuresis

mPGES-1-derived PGE₂ mediates dehydration natriuresis

M. bovisBCG induced expression of COX-2 involves nitric oxide-dependent and -independent signaling pathways

Is There a Role for PGE2 in Urinary Concentration?

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PGE2 enhances cytokine-elicited nitric oxide production in mouse cortical collecting duct cells

Cited by 9 publications

References 42 publications

mPGES-1-derived PGE2 mediates dehydration natriuresis

mPGES-1-derived PGE2 mediates dehydration natriuresis

M. bovisBCG induced expression of COX-2 involves nitric oxide-dependent and -independent signaling pathways

Is There a Role for PGE2 in Urinary Concentration?

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mPGES-1-derived PGE₂ mediates dehydration natriuresis

mPGES-1-derived PGE₂ mediates dehydration natriuresis