Prostaglandin E2 Stimulates Granulocyte Colony-Stimulating Factor Production via the Prostanoid EP2 Receptor in Mouse Peritoneal Neutrophils

Sugimoto, Yukihiko; Fukada, Yoko; Mori, Daisuke; Tanaka, Satoshi; Yamane, Haruki; Okuno, Yasushi; Deai, Katsuya; Tsuchiya, Soken; Tsujimoto, Gozoh; Ichikawa, Atsushi

doi:10.4049/jimmunol.175.4.2606

Cited by 20 publications

(14 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PGE 2 stimulates IL-1␤ expression in macrophages through activation of adenylate cyclase (Ohmori et al, 1990). Furthermore, PGE 2 accelerates release of IL-6, IL-10, and G-CSF from neutrophils and macrophages via EP 2 and EP 4 receptors (Yamane et al, 2000;Treffkorn et al, 2004;Sugimoto et al, 2005). In this study, we showed that NS-398 significantly decreased mRNA levels of IL-1␤, IL-6, and G-CSF in the exudate leukocytes and that the EP 2 receptor agonist reversed the effect of NS-398 on the cytokine mRNA levels.…”

Section: Discussionsupporting

confidence: 53%

Contribution of the Prostaglandin E₂/E-Prostanoid 2 Receptor Signaling Pathway in Abscess Formation in Rat Zymosan-Induced Pleurisy

Inada¹,

Arai²,

Kawamura³

et al. 2009

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Abscess formation is a classic host response to infection by many pathogenic microorganisms. Here, we studied the role of prostaglandins (PGs) and their signal transduction in abscess formation. Zymosan was injected into the pleural cavity of rats. Expression of enzymes involved in PG synthesis, their receptors, and cytokines in exudate leukocytes and abscesses were analyzed by polymerase chain reaction, Western blotting, and immunohistochemistry. Treatment with ketorolac, a cyclooxygenase (COX)-1 inhibitor, or N- [2-cyclohexyloxy-4-nitrophenyl] methanesulfonamide (NS-398), a COX-2 inhibitor, reduced the size of abscesses and the number of cells recovered from the abscess. COX-2 was detected in leukocytes of the exudate and a marginal area of abscesses. Among detected terminal PG synthases, the major one was cytosolic PGE synthase. Membrane-bound PGE synthase (mPGES)-1 was detected in cells that were similar to the COX-2-expressing cells in morphology and localization. A high level of the E-prostanoid (EP) 2 receptor and a low level of the EP 4 receptor were detected. The expression pattern of the EP 2 receptor paralleled that of COX-2 and mPGES-1. 11,15-O-Dimethyl PGE 2 (ONO-AE1-259), an EP 2 receptor agonist, and rolipram, a phosphodiesterase type-4 inhibitor, reversed the effects of COX inhibitors on abscess formation. In contrast, 16-(3-methoxymethyl) phenyl--tetranor-3,7-dithia PGE 1 (ONO-AE1-329), an EP 4 receptor agonist, did not reverse the effects of NS-398. Moreover, NS-398 reduced the mRNA levels in exudate leukocytes of some proinflammatory and fibrogenic cytokines, which was reversed by ONO-AE1-259. These results suggest that PGE 2 generated via COX-1 and COX-2 may interact with the EP 2 receptor and may up-regulate in cAMP-dependent fashion the production of cytokines that promote abscess formation.Abscess formation is a complex host response that involves fibrin deposition and recruitment of leukocytes as well as other processes that have not been completely elucidated. It has been viewed as a host defense strategy: a fibrous capsule localizes invading microorganisms and presumably protects the host from disseminated infection. However, microorganisms sequestered within a fibrin capsule are protected from normal host clearance mechanisms, thereby permitting unopposed proliferation of the microorganisms (Brook, 2002). Thus, an abscess is difficult to treat with antimicrobial therapy and usually requires surgical intervention.Prostanoids, including prostaglandin (PG) and thromboxane (TX), are lipid mediators that regulate numerous processes in the body, including modulation of immune and inflammatory responses. Prostanoids are produced when arachidonic acid is released from the plasma membrane by phospholipase A 2 and metabolized by cyclooxygenases (COXs) and specific terminal PG synthases. Prostanoid production depends on the activity of two COX isoforms, COX-1 and COX-2. COX-1 is present in most cells and its expression is constitutive. In contrast, COX-2 expression is low or undetectabl...

show abstract

Section: Discussionsupporting

confidence: 53%

Contribution of the Prostaglandin E₂/E-Prostanoid 2 Receptor Signaling Pathway in Abscess Formation in Rat Zymosan-Induced Pleurisy

Inada¹,

Arai²,

Kawamura³

et al. 2009

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…Previous studies have identified that PGE 2 can positively regulate expression of IL-6, KC, G-CSF, and MIP-1␣ during peritonitis (57)(58)(59). Using a casein-induced model of peritonitis, Sugimoto et al demonstrated that the amounts of PGE 2 are significantly increased in the peritoneal cavity (65). This PGE 2 increase correlated well with increased G-CSF expression, followed by infiltration of neutrophils into the peritoneal cavity; significantly smaller amounts of PGE 2 , G-CSF, and neutrophils were found in the peritoneal cavity after administration of indomethacin.…”

Section: Discussionmentioning

confidence: 91%

Candida albicans-Staphylococcus aureus Polymicrobial Peritonitis Modulates Host Innate Immunity

2013

View full text Add to dashboard Cite

bDespite advances in medical device fabrication and antimicrobial treatment therapies, fungal-bacterial polymicrobial peritonitis remains a serious complication for surgery patients, those on peritoneal dialysis, and the critically ill. Using a murine model of peritonitis, we have demonstrated that monomicrobial infection with Candida albicans or Staphylococcus aureus is nonlethal. However, coinfection with these same doses leads to a 40% mortality rate and increased microbial burden in the spleen and kidney by day 1 postinfection. Using a multiplex enzyme-linked immunosorbent assay, we have also identified a unique subset of innate proinflammatory cytokines (interleukin-6, granulocyte colony-stimulating factor, keratinocyte chemoattractant, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1␣) that are significantly increased during polymicrobial versus monomicrobial peritonitis, leading to increased inflammatory infiltrate into the peritoneum and target organs. Treatment of coinfected mice with the cyclooxygenase (COX) inhibitor indomethacin reduces the infectious burden, proinflammatory cytokine production, and inflammatory infiltrate while simultaneously preventing any mortality. Further experiments demonstrated that the immunomodulatory eicosanoid prostaglandin E 2 (PGE 2 ) is synergistically increased during coinfection compared to monomicrobial infection; indomethacin treatment also decreased elevated PGE 2 levels. Furthermore, addition of exogenous PGE 2 into the peritoneal cavity during infection overrode the protection provided by indomethacin and restored the increased mortality and microbial burden. Importantly, these studies highlight the ability of fungal-bacterial coinfection to modulate innate inflammatory events with devastating consequences to the host.

show abstract

“…Of the ϳ8,544 genes represented on the cDNA microarray (Incyte Rat GEM), the genes that showed differential expression values greater than 1.5 or less than Ϫ1.5 were selected (18,23). Similar analysis was repeated independently, and the genes showing similar responses to PGE 2 were regarded as differentially expressed genes.…”

Section: Resultsmentioning

confidence: 99%

Prostaglandin E2 Attenuates Preoptic Expression of GABAA Receptors via EP3 Receptors

Tsuchiya

Oka

Nakamura

et al. 2008

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Prostaglandin E 2 (PGE 2 ) has been shown to produce fever by acting on EP3 receptors within the preoptic area of the brain. However, there is little information about the molecular events downstream of EP3 activation in preoptic neurons. As a first step toward this issue, we examined PGE 2 -induced gene expression changes at single-cell resolution in preoptic neurons expressing EP3. Brain sections of the preoptic area from PGE 2 -or saline-injected rats were stained with an anti-EP3 antibody, and the cell bodies of EP3-positive neurons were dissected and subjected to RNA amplification procedures. Microarray analysis of the amplified products demonstrated the possibility that gene expression of ␥-aminobutyric acid type A (GABA A ) receptor subunits is decreased upon PGE 2 injection. Indeed, we found that most EP3-positive neurons in the mouse preoptic area are positive for the ␣2 or ␥2 GABA A receptor subunit. Moreover, PGE 2 decreased the preoptic gene expression of these GABA A subunits via an EP3-dependent and pertussis toxin-sensitive pathway. PGE 2 also attenuated the preoptic protein expression of the ␣2 subunit in wild-type but not in EP3-deficient mice. These results indicate that PGE 2 -EP3 signaling elicits G i/o activation in preoptic thermocenter neurons, and we propose the possibility that a rapid decrease in preoptic GABA A expression may be involved in PGE 2 -induced fever.Body temperature is controlled by central and peripheral mechanisms such as heart rate, muscle tone, metabolic rate, vasoconstrictor action, and shivering, thereby reaching a new thermoregulatory set point. Fever is characterized as an elevation in body temperature by 1-2°C and is one of the representative systemic responses against inflammation (1, 2). Fever is a clinically important symptom associated with many serious diseases such as infections, toxonosis, and neoplasia. Fever responses are initiated by cytokines such as interleukin-1 and interleukin-6, which are released from immune cells activated by exogenous pyrogens such as lipopolysaccharide. These cytokines act on the brain vasculature and therein stimulate prostaglandin (PG) 4 E 2 production (3). PGE 2 has been shown to elicit fever, because aspirin-like drugs exert anti-pyretic actions through the suppression of PGE 2 biosynthesis by inhibiting cyclooxygenase, a rate-limiting enzyme of PGE 2 synthesis (4, 5). PGE 2 displays a broad range of actions including fever generation through its binding to specific receptors on target cells. There are four PGE receptor subtypes, EP1, EP2, EP3, and EP4, all of which are expressed in the central nervous system (6). We have shown that EP3 plays a pivotal role in inflammation-associated fever, because EP3-deficient mice fail to exhibit fever in response to central administration of PGE 2 and interleukin-1␤ or peripheral administration of interleukin-1␤ and lipopolysaccharide (7,8). However, there is still little information about the molecular events downstream of PGE 2 -EP3 signaling in the central nervous system.The preoptic a...

show abstract

Prostaglandin E2 Stimulates Granulocyte Colony-Stimulating Factor Production via the Prostanoid EP2 Receptor in Mouse Peritoneal Neutrophils

Cited by 20 publications

References 44 publications

Contribution of the Prostaglandin E₂/E-Prostanoid 2 Receptor Signaling Pathway in Abscess Formation in Rat Zymosan-Induced Pleurisy

Contribution of the Prostaglandin E₂/E-Prostanoid 2 Receptor Signaling Pathway in Abscess Formation in Rat Zymosan-Induced Pleurisy

Candida albicans-Staphylococcus aureus Polymicrobial Peritonitis Modulates Host Innate Immunity

Prostaglandin E2 Attenuates Preoptic Expression of GABAA Receptors via EP3 Receptors

Contact Info

Product

Resources

About

Prostaglandin E2 Stimulates Granulocyte Colony-Stimulating Factor Production via the Prostanoid EP2 Receptor in Mouse Peritoneal Neutrophils

Cited by 20 publications

References 44 publications

Contribution of the Prostaglandin E2/E-Prostanoid 2 Receptor Signaling Pathway in Abscess Formation in Rat Zymosan-Induced Pleurisy

Contribution of the Prostaglandin E2/E-Prostanoid 2 Receptor Signaling Pathway in Abscess Formation in Rat Zymosan-Induced Pleurisy

Candida albicans-Staphylococcus aureus Polymicrobial Peritonitis Modulates Host Innate Immunity

Prostaglandin E2 Attenuates Preoptic Expression of GABAA Receptors via EP3 Receptors

Contact Info

Product

Resources

About

Contribution of the Prostaglandin E₂/E-Prostanoid 2 Receptor Signaling Pathway in Abscess Formation in Rat Zymosan-Induced Pleurisy

Contribution of the Prostaglandin E₂/E-Prostanoid 2 Receptor Signaling Pathway in Abscess Formation in Rat Zymosan-Induced Pleurisy