Regulation of inflammation in cancer by eicosanoids

Greene, Emily; Huang, Sui; Serhan, Charles N.; Panigrahy, Dipak

doi:10.1016/j.prostaglandins.2011.08.004

Cited by 281 publications

(250 citation statements)

References 173 publications

(233 reference statements)

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“…There is, however, another prominent enzymatic pathway for which arachidonic acid is the substrate: the cytochrome P450 (CYP) system (2). This eicosanoid pathway consists of two main branches: ω-hydroxylases, which convert arachidonic acid into hydroxyeicosatetraenoic acids, and epoxygenases, which convert it to epoxyeicosatrienoic acids (EETs) (4,5). Although the COX-and LOX-derived eicosanoids have been intensely studied in tissue regeneration (6,7), the investigation of CYP-derived eicosanoids has primarily focused on inflammation and cardiovascular functions (3).…”

mentioning

confidence: 99%

Epoxyeicosanoids promote organ and tissue regeneration

Panigrahy

Kalish

Huang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Epoxyeicosatrienoic acids (EETs), lipid mediators produced by cytochrome P450 epoxygenases, regulate inflammation, angiogenesis, and vascular tone. Despite pleiotropic effects on cells, the role of these epoxyeicosanoids in normal organ and tissue regeneration remains unknown. EETs are produced predominantly in the endothelium. Normal organ and tissue regeneration require an active paracrine role of the microvascular endothelium, which in turn depends on angiogenic growth factors. Thus, we hypothesize that endothelial cells stimulate organ and tissue regeneration via production of bioactive EETs. To determine whether endothelial-derived EETs affect physiologic tissue growth in vivo, we used genetic and pharmacological tools to manipulate endogenous EET levels. We show that endothelial-derived EETs play a critical role in accelerating tissue growth in vivo, including liver regeneration, kidney compensatory growth, lung compensatory growth, wound healing, corneal neovascularization, and retinal vascularization. Administration of synthetic EETs recapitulated these results, whereas lowering EET levels, either genetically or pharmacologically, delayed tissue regeneration, demonstrating that pharmacological modulation of EETs can affect normal organ and tissue growth. We also show that soluble epoxide hydrolase inhibitors, which elevate endogenous EET levels, promote liver and lung regeneration. Thus, our observations indicate a central role for EETs in organ and tissue regeneration and their contribution to tissue homeostasis.

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mentioning

confidence: 99%

Epoxyeicosanoids promote organ and tissue regeneration

Panigrahy

Kalish

Huang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

128

124

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“…This marginal MCC deficiency ROS interactome suggests chronic activation of inflammatory and immune signalling responses. Chronic activated of pro-inflammatory signalling has been associated with compromised cellular membrane integrity and the development of cancer [69,73] Both the complete set of 1277 and the subset of 48 HuChrX associated differentially expressed transcript IDs indicated increased inflammatory signalling responses and impaired cellular maintenance and repair activity that could imply compromised membrane integrity (Figure 4a; Supplementary Table 6). It is important to note that persistent oxidative stress in addition to an already compromised membrane repair capacity could severely affect membrane integrity.…”

Section: Discussionmentioning

confidence: 99%

“…However, the induction of GGT suggests elevated levels of leukotriene D4 and the suppression of PTGES3 suggests elevated levels of prostacyclin which both have strong pro-inflammatory properties [93]. Imbalances in eicosanoid metabolism signalling have been detected in individuals with a weak tolerance to environmental factors and susceptibility to environmental stressors that often result in asthma [94][95][96][97], allergy, eczema [98][99][100], arthritis [81] as well as the development of cancer [73] and might also play a role in the development of non-specific symptoms of marginal MCC deficiency. Therefore, life-long monitoring of ROS levels of individuals with MCC deficiency along with the administration of anti-oxidants to prevent and manage deleterious secondary signalling responses may be beneficial as previously proposed (Figure 3) [55,56,60,64,65,101].…”

Section: Discussionmentioning

confidence: 99%

Biochemical Characterisation and Whole Genome Expression Profiling of Cultured Skin Fibroblasts from Two South African Adults with Urinary 3-Hydroxyisovaleric Acid and 3-Methylcrotonylglycine

Berg¹,

Erasmus²,

Suormala³

et al. 2016

J Rare Disord Diagn Ther

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We report on the first case of marginal 3-methylcrotonyl-CoA carboxylase (MCC) deficiency in South Africa. Urinary 3-hydroxyisovaleric acid and 3-methylcrotonylglycine were detected in four males of a non-consanguineous family. Only the index patient (NWU001) had non-specific symptoms, the others were asymptomatic. The inherited metabolite profile and partially reduced MCC activity were indicative of marginal MCC deficiency. In vivo L-leucine loading confirmed a reduced flux through the leucine degradation pathway. No known deleterious mutations were detected in the open reading frames of MCCC1 and MCCC2. NWU001 was heterozygous for a SNP in MCCC1 (rs2270968; c.1391A>C, p.H464P). NWU002 was heterozygous for a MCCC2 splice variant which skips exon 7 and causes an in frame deletion of 38 amino acids that is identical to a predicted shorter MCCC2 isoform-2 (Q9HCC0-2). Whole genome expression profiles from cultured skin fibroblasts of NWU001 and NWU002 and two healthy adults using Affymetrix ® HuExST1.0 arrays detected 14237 significantly differentially expressed transcript IDs of which only 1277 have known annotation and gene association. The underlying molecular interactions, secondary signalling responses and functional relationships of these 1277 transcripts were inspected following a knowledge-based functional analyses approach using Ingenuity Pathway Analysis software. The transcriptome had a footprint of oxidative stress, disruption of energy homeostasis, inflammation, impaired cellular maintenance and repair mechanisms. Of note was the significant up regulation of the fatty acid amide hydrolase variant 2 (FAAH2) HuChrX transcript in the anandamide degradation canonical pathway. The observations that the two MCC transcripts were not significantly differentially expressed and that more than 90% of the significantly differently expressed transcripts are still poorly annotated further support the notion that secondary factors other than the MCC loci impact on the MCC deficiency phenome.

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“…In contrast, COX-2 may be induced by a series of pro-inflammatory stimuli and its role in the progress of inflammation, fever and pain has been known [12]. Furthermore, COX-2 has been targeted in many cancers including: colon cancer, colorectal cancer, breast cancer, gliomas, prostate cancer, esophageal carcinoma, pancreatic cancer, lung carcinoma, gastric carcinoma, ovarian cancer, Kaposi's sarcoma and melanoma [13].…”

Section: Eicosanoid Pathwaymentioning

confidence: 99%

“…[14,15]. 12-HETE is implicated in regulation of platelet aggregation, angiogenesis, as well as the progression of several human diseases like various cancers, rheumatoid arthritis and psoriasis [13,16,17]. Also, 12-HETE is known to take part in the metastatic cascade as a crucial intracellular signalling molecule which activates protein kinase C and mediates the biological functions of growth factors and cytokines.…”

Section: Eicosanoid Pathwaymentioning

confidence: 99%