Prostaglandin E2 as a Modulator of Lymphocyte Mediated Inflammatory and Humoral Responses

Kaur, Kuljeet; Harris, Sarah G.; Padilla, Josué; Graf, Beth A.; Phipps, Richard P.

doi:10.1007/978-1-4615-4793-8_59

Cited by 18 publications

(14 citation statements)

References 15 publications

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“…Furthermore, PGE 2 stimulates the production of IL-12 by human dendritic cells in a dose-dependent manner (64), and it inhibits Th2 cytokine secretion by Con A-stimulated murine spleen cells (65). Conversely, it has also been suggested that PGE 2 can inhibit the production of the Th1 cytokines IL-2 and IFN-␥ (66). The ability of a certain prostanoid to affect T cell functions may depend on the engagement of different G proteincoupled cell-surface receptors (10).…”

Section: Discussionmentioning

confidence: 99%

Cyclooxygenase-2 Deficiency Enhances Th2 Immune Responses and Impairs Neutrophil Recruitment in Hepatic Ischemia/Reperfusion Injury

Hamada

Tsuchihashi

Avanesyan

et al. 2008

The Journal of Immunology

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Cyclooxygenase-2 (COX-2) is a prostanoid-synthesizing enzyme that is critically implicated in a variety of pathophysiological processes. Using a COX-2-deficient mouse model, we present data that suggest that COX-2 has an active role in liver ischemia/reperfusion (I/R) injury. We demonstrate that COX-2-deficient mice had a significant reduction in liver damage after I/R insult. The inability of COX-2−/− to elaborate COX-2 products favored a Th2-type response in these mice. COX-2−/− livers after I/R injury showed significantly decreased levels of IL-2, as well as IL-12, a cytokine known to have a central role in Th1 effector cell differentiation. Moreover, such livers expressed enhanced levels of the anti-inflammatory cytokine IL-10, shifting the balance in favor of a Th2 response in COX-2-deficient mice. The lack of COX-2 expression resulted in decreased levels of CXCL2, a neutrophil-activating chemokine, reduced infiltration of MMP-9-positive neutrophils, and impaired late macrophage activation in livers after I/R injury. Additionally, Bcl-2 and Bcl-xL were normally expressed in COX-2−/− livers after injury, whereas respective wild-type controls were almost depleted of these two inhibitors of cell death. In contrast, caspase-3 activation and TUNEL-positive cells were depressed in COX-2−/− livers. Therefore, our data support the concept that COX-2 is involved in the pathogenic events occurring in liver I/R injury. The data also suggest that potential valuable therapeutic approaches in liver I/R injury may result from further studies aimed at identifying specific COX-2-derived prostanoid pathways.

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Section: Discussionmentioning

confidence: 99%

Cyclooxygenase-2 Deficiency Enhances Th2 Immune Responses and Impairs Neutrophil Recruitment in Hepatic Ischemia/Reperfusion Injury

Hamada

Tsuchihashi

Avanesyan

et al. 2008

The Journal of Immunology

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“…In vitro studies suggest that PGE 2 promotes the development of a Th2 response. Interestingly, PGE 2 can inhibit the production of the Th1 cytokines IL-2 and IFN-γ, shifting the balance in favor of a Th2 response that enhances IL-4 and IL-5 production and facilitates Ig class switching to IgE (22). However, other studies have suggested that PGE 2 inhibits Th2 cytokine secretion and IgE production by B cells (20,23).…”

Section: Figurementioning

confidence: 99%

Mixed messages: modulation of inflammation and immune responses by prostaglandins and thromboxanes

Tilley¹,

Coffman²,

Koller³

2001

J. Clin. Invest.

386

385

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Prostaglandins and their precursorsVirtually every organism has evolved mechanisms by which, upon stimulation, lipids are released from plasma membranes and metabolized into mediators capable of changing cellular physiology. As these lipids are present at the first site exposed to external challenge, they provide an ideal substrate for the synthesis of defensive mediators and homeostatic regulators. One such group of lipid mediators is the prostanoids, including the prostaglandins (PGs) and thromboxanes (TXs).Soon after their initial isolation and characterization, the ability of prostanoids to influence inflammation and immune responses was recognized. For example, administration of prostanoids, either alone or in combination, could reproduce the cardinal signs of inflammation. Because they could induce inflammatory changes when injected into tissue and were present at high levels in inflamed lesions, prostanoids were initially categorized as proinflammatory mediators. As our understanding of prostanoid physiology has evolved, it has become clear that these mediators can act to both promote and inhibit inflammation. Thus, it is more accurate to envision these molecules as part of a complex regulatory network that modulates the actions of immune cells and the surrounding microenvironment. Their overall impact in an individual inflammatory response will depend on several factors, including the level of immune cell activation, the presence of other mediators, and the physiological state of the organism.Our ability to dissect the role of prostanoids in complex inflammatory responses has been substantially advanced by the recent development of mouse lines with targeted mutations of genes encoding enzymes and receptors in the prostanoid pathway. In this review we will develop the concept that prostanoids are both effectors and regulators of inflammation, emphasizing new information provided by these mouse models. Production of prostanoids during inflammationProstanoids are produced when arachidonic acid (AA) is released from the plasma membrane by phospholipases and metabolized by cyclooxygenases (COXs) and specific isomerases. During an inflammatory response, both the level and the profile of prostanoid production can change dramatically. While prostanoid levels are generally very low in uninflamed tissues, they increase

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“…Yet, PGE 2 is well known to inhibit IFN-γ production by T cells [5][6][7][8]; therefore, we suspected that the expected mode of T cell stimulation (IL-12/IL-18) [40] in the present co-culture situation might be related to the lack of the effect on IFN-γ, instead of the commonly employed T cell stimulation (anti-CD3/anti-CD28 antibody). If this is true, PGE 2 should have no effect on IFN-γ production when purified CD4 + T cells are stimulated with IL-12/IL-18, but should have an effect with anti-CD3/CD28 antibodies.…”

Section: Discussionmentioning

confidence: 64%

“…For example, PGE 2 can exacerbate inflammation by facilitating plasma protein extravasations via vasodilatation and increased vascular permeability [3,4]. On the other hand, PGE 2 may suppress interferon-gamma (IFN-γ) production from natural killer (NK) cells, as well as helper T (Th) cells, which may lead to the downregulation of innate immunity and the deviation of adaptive immunity away from the Th1 type [3,[5][6][7][8]. To further complicate things, in certain situations, PGE 2 can facilitate Th1 cell differentiation and Th17 cell expansion, leading to a progression of autoimmune diseases [9,10].…”

Section: Introductionmentioning

confidence: 99%

Promotion of interferon-gamma production by natural killer cells via suppression of murine peritoneal macrophage prostaglandin E2 production using intravenous anesthetic propofol

Inada

Kubo

Shingu

2010

International Immunopharmacology

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Prostaglandin E2 as a Modulator of Lymphocyte Mediated Inflammatory and Humoral Responses

Cited by 18 publications

References 15 publications

Cyclooxygenase-2 Deficiency Enhances Th2 Immune Responses and Impairs Neutrophil Recruitment in Hepatic Ischemia/Reperfusion Injury

Cyclooxygenase-2 Deficiency Enhances Th2 Immune Responses and Impairs Neutrophil Recruitment in Hepatic Ischemia/Reperfusion Injury

Mixed messages: modulation of inflammation and immune responses by prostaglandins and thromboxanes

Promotion of interferon-gamma production by natural killer cells via suppression of murine peritoneal macrophage prostaglandin E2 production using intravenous anesthetic propofol

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