Prostaglandin synthases: recent developments and a novel hypothesis

Helliwell, Rachel J. A.; Adams, Lowell; Mitchell, Murray D.

doi:10.1016/j.plefa.2003.04.002

Cited by 185 publications

(137 citation statements)

References 157 publications

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“…These all implicate the potential role of PGI 2 analogs in treating asthma by altering the function of mDCs. D 1 8 : 4 3 3 -4 4 4 , 2 0 1 2 E F F E C T O F P G I 2 A N A L O G S O N H U M A N Prostaglandins are derived from arachidonic acid by stepwise conversion and are important endogenous inflammatory mediators, controlling immune stimulation and inflammation by the effects of prostaglandins on cytokine production (32). IP receptor activation by PGI 2 or its analogs can result in vasodilation and antithrombotic and antiinflammatory effects (14,33).…”

Section: Discussionmentioning

confidence: 99%

Effect of Prostaglandin I2 Analogs on Cytokine Expression in Human Myeloid Dendritic Cells via Epigenetic Regulation

Kuo

Lin

Yang

et al. 2011

Mol Med

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Section: Discussionmentioning

confidence: 99%

Effect of Prostaglandin I2 Analogs on Cytokine Expression in Human Myeloid Dendritic Cells via Epigenetic Regulation

Kuo

Lin

Yang

et al. 2011

Mol Med

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“…PGs are generated by stepwise conversion of arachidonic acid into a series of products, including PGG, PGH, PGD 2 , PGE 2 , PGF 2a and PGI 2 , via the action of the cyclooxygenases and other specific enzymes [15,16]. PGs are generally regarded as proinflammatory molecules, but PGE 2 can have anti-inflammatory and anti-asthmatic effects via the E prostanoid receptor 3 [17].…”

Section: Discussionmentioning

confidence: 99%

Regulation of cytokine expression in human plasmacytoid dendritic cells by prostaglandin I2 analogues

Yt²,

Jl³

et al. 2008

European Respiratory Journal

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Plasmacytoid dendritic cells (pDCs) are critical in controlling adaptive immunity, but the mechanisms governing cytokine expression remain incompletely defined. Analogues of prostaglandin (PG)I 2 , such as iloprost, can modulate functions of myeloid dendritic cells, but their involvement in the regulation of human pDCs remains unknown. To this end, the regulatory role of PGI 2 analogues on cytokine expression in pDCs was investigated.Circulating pDCs were magnetically sorted with BDCA-4 cell isolation kits from human peripheral blood mononuclear cells and treated with varying concentrations of iloprost with or without the addition of Toll-like receptor agonists, or an I prostanoid (IP) receptor antagonist, CAY10449. The levels of tumour necrosis factor (TNF)-a, interferon (IFN)-a and interleukin (IL)-10 were measured by ELISA.Iloprost induced IL-10 expression, but suppressed CpG oligodeoxynucleotide-(or imiquimod-) induced TNF-a and IFN-a production in pDCs. This effect was reversed by the addition of CAY10449. Forskolin, a cyclic adenosine monophosphate activator, conferred a similar modulating effect to that noted in iloprost-treated pDCs, although a higher concentration of forskolin was required to exert the same effect.Iloprost enhanced interleukin-10 and suppressed Toll-like receptor-mediated tumour necrosis factor-a and interferon-a production of human plasmacytoid dendritic cells via the I prostanoid receptor and, in part, the cyclic adenosine monophosphate pathway.

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“…These enzymes mediate the synthesis of the prostanoid precursor, prostaglandin H 2 (PGH 2 ) (Fitzpatrick, 2004). Metabolism of PGH 2 leads to the generation of PGD 2 , PGE 2 , PGF 2 , PGI 2 and thromboxane A 2 which are synthesized by PGD 2 synthase, PGE 2 synthase, PGF 2 synthase, PGI 2 synthase and thromboxane A 2 synthase, respectively (Helliwell et al, 2004). Exposure to UVB light, which is known to cause cutaneous inflammation and cancer (Hruza and Pentland, 1993), has been reported to upregulate COX-2 in human and mouse skin (Buckman et al, 1998;Isoherranen et al, 1999;Chen et al, 2001;Bachelor et al, 2005), a process linked to many of its biological effects (Fitzpatrick, 2004).…”

Section: Introductionmentioning

confidence: 99%

UVB light upregulates prostaglandin synthases and prostaglandin receptors in mouse keratinocytes

Black

Gray

Shakarjian

et al. 2008

Toxicology and Applied Pharmacology

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Prostaglandins belong to a class of cyclic lipid-derived mediators synthesized from arachidonic acid via COX-1, COX-2 and various prostaglandin synthases. Members of this family include prostaglandins such as PGE 2 , PGF 2α , PGD 2 and PGI 2 (prostacyclin) as well as thromboxane. In the present studies we analyzed the effects of UVB on prostaglandin production and prostaglandin synthase expression in primary cultures of undifferentiated and calcium-differentiated mouse keratinocytes. Both cell types were found to constitutively synthesize PGE 2 , PGD 2 and the PGD 2 metabolite PGJ 2 . Twenty-four hr after treatment with UVB (25 mJ/cm 2 ), production of PGE 2 and PGJ 2 increased, while PGD 2 production decreased. This was associated with increased expression of COX-2 mRNA and protein. UVB (2.5 -25 mJ/cm 2 ) also caused marked increases in mRNA expression for the prostanoid synthases PGDS, mPGES-1, mPGES-2, PGFS and PGIS, as well as expression of receptors for PGE 2 (EP1 and EP2), PGD 2 (DP and CRTH2) and prostacyclin (IP). UVB was more effective in inducing COX-2 and DP in differentiated cells and EP1 and IP in undifferentiated cells. UVB readily activated keratinocyte PI-3-kinase (PI3K)/Akt, JNK and p38 MAP signaling pathways which are known to regulate COX-2 expression. While inhibition of PI3K suppressed UVB-induced mPGES-1 and CRTH2 expression, JNK inhibition suppressed mPGES-1, PGIS, EP2 and CRTH2, and p38 kinase inhibition only suppressed EP1 and EP2. These data indicate that UVB modulates expression of prostaglandin synthases and receptors by distinct mechanisms. Moreover, both the capacity of keratinocytes to generate prostaglandins and their ability to respond to these lipid mediators are stimulated by exposure to UVB.

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Prostaglandin synthases: recent developments and a novel hypothesis

Cited by 185 publications

References 157 publications

Effect of Prostaglandin I2 Analogs on Cytokine Expression in Human Myeloid Dendritic Cells via Epigenetic Regulation

Effect of Prostaglandin I2 Analogs on Cytokine Expression in Human Myeloid Dendritic Cells via Epigenetic Regulation

Regulation of cytokine expression in human plasmacytoid dendritic cells by prostaglandin I2 analogues

UVB light upregulates prostaglandin synthases and prostaglandin receptors in mouse keratinocytes

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