Regulation of T-lymphocyte mitogenesis by the leukocyte product 15-hydroxy-eicosatetraenoic acid (15-HETE)

Bailey, J. Martyn; Bryant, Robert W.; Low, Chow-Eng; Pupillo, M.; Vanderhoek, Jack Y.

doi:10.1016/0008-8749(82)90203-9

Cited by 106 publications

(20 citation statements)

References 12 publications

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“…Furthermore, we found that 15-HETE levels are only upregulated in IV HEEs when compared with crtl HEEs (Figure 4c). 15-HETE inhibits T-cell proliferation and reduces synthesis of leukotriene B4 by leukocytes (Bailey et al, 1982; Camp and Fincham, 1985; Chen et al, 2003; Gualde et al, 1985; Hsi et al, 2001; Vanderhoek et al, 1980; Waldman et al, 1989). Moreover, 15-HETE exerts anti-inflammatory effects; for example, it ameliorates psoriasis when injected into skin (Fogh et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

Alterations in Epidermal Eicosanoid Metabolism Contribute to Inflammation and Impaired Late Differentiation in FLG-Mutated Atopic Dermatitis

Blunder

Rühl

Moosbrugger‐Martinz

et al. 2017

Journal of Investigative Dermatology

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Loss-of-function mutations in the FLG gene cause ichthyosis vulgaris (IV) and represent the major predisposing genetic risk factor for atopic dermatitis (AD). Although both conditions are characterized by epidermal barrier impairment, AD also exhibits signs of inflammation. This work was aimed at delineating the role of FLG loss-of-function mutations on eicosanoid metabolism in IV and AD. Using human epidermal equivalents (HEEs) generated with keratinocytes isolated from nonlesional skin of patients with FLG wild-type AD (WT/WT), FLG-mutated AD (FLG/WT), IV (FLG/FLG), or FLG WT control skin, we assessed the potential autocrine role of epidermal-derived eicosanoids in FLG-associated versus FLG-WT AD pathogenesis. Ultrastructural analyses demonstrated abnormal stratum corneum lipid architecture in AD and IV HEEs, independent of FLG genotype. Both AD (FLG/WT) and IV (FLG/FLG) HEEs showed impaired late epidermal differentiation. Only AD (FLG/WT) HEEs exhibited significantly increased levels of inflammatory cytokines. Analyses of lipid mediators revealed increased arachidonic acid and 12-lipoxygenase metabolites. Whereas treatment of control HEEs with arachidonic acid increased expression of inflammatory cytokines, 12-hydroxy-eicosatetraenoic acid attenuated expression of late differentiation markers. Thus, FLG mutations lead to alterations in epidermal eicosanoid metabolism that could serve as an autocrine trigger of inflammation and impaired late epidermal differentiation in AD.

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Section: Discussionmentioning

confidence: 99%

Alterations in Epidermal Eicosanoid Metabolism Contribute to Inflammation and Impaired Late Differentiation in FLG-Mutated Atopic Dermatitis

Blunder

Rühl

Moosbrugger‐Martinz

et al. 2017

Journal of Investigative Dermatology

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“…These last three leukotrienes, which are cysteinyl leukotrienes, constitute the biologically active mixture known as slow reacting substance of anaphylaxis (SRSA). Other important lipoxygenase pathways yield 15-HPETE in neutrophils, eosinophils and reticulocytes [83,84,85] and 12-HPETE in platelets and lymphocytes [86,87]. These hydroperoxides are reduced by peroxidases to the corresponding hydroxy fatty acids (HETEs).…”

Section: Prostanoids In Physiological and Pathological Processesmentioning

confidence: 99%

New Trends in Dual 5-LOX / COX Inhibition

Leval¹,

Julémont²,

Delarge³

et al. 2002

CMC

109

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Dual inhibitors are drugs able to block both the COX and the 5-LOX metabolic pathways. The interest of developing such compounds is supported by a large number of pharmacological studies. Compared to COX or LOX pathways single inhibitors, dual inhibitors present at least two major advantages. First, dual inhibitors, by acting on the two major arachidonic acid metabolic pathways, possess a wide range of anti-inflammatory activity. Secondly, dual inhibitors appear to be almost exempt from gastric toxicity, which is the most troublesome side effect of COX inhibitors. The mechanism of their gastric-sparing properties is not completely understood, although it has been demonstrated that leukotrienes significantly contribute to the gastric epithelial injury. Finally, both COX and LOX derivatives (prostanoids and leukotrienes, respectively) are involved in other diseases than inflammation such as cancer proliferation where the use of dual inhibitors could be an interesting approach.

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“…The stimulation of a 1 -adrenoceptors causes arachidonic acid release (Nishio et al, 1996c) and metabolites produced via the lipoxygenase pathway may be involved in the proliferation of VSMCs (Cornwell et al, 1979;Bailey et al, 1982).…”

Section: Introductionmentioning

confidence: 99%

The regulation of mitogenesis and apoptosis in response to the persistent stimulation of α₁‐adrenoceptors: a possible role of 15‐lipoxygenase

Nishio

Watanabe

1997

British J Pharmacology

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Activation of α1‐adrenoceptor stimulation regulates eicosanoid metabolism and growth in vascular smooth muscle cells (VSMCs). The purpose of this study was to investigate the functional implications of lipoxygenase pathway in α1‐adrenoceptor‐stimulated VSMCs growth through mutually exclusive biological functions, that is cell proliferation and cell death. Phenylephrine (10 μM), a specific α1‐adrenoceptor agonist, enhanced [3H]‐thymidine incorporation by 300% above basal. Nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, caused 36 and 50% decrease in phenylephrine (10 μM)‐stimulated [3H]‐thymidine incorporation at concentrations of 1 μM and 10 μM respectively. Inversely, treatment of phenylephrine (10 μM)‐stimulated VSMCs with NDGA induced DNA fragmentation in a dose‐dependent fashion. The level of induction of DNA fragmentation by NDGA was 225, 319 and 406% above the phenylephrine (10 μM)‐level at concentrations of 0.1 μM, 1 μM and 10 μM, respectively. This induction of DNA fragmentation was partially prevented by exogenous 15‐hydroxyeicosatetraenoic acid (15‐HETE). The inhibition of apoptosis was 53 and 63% at concentrations of 5 μM and 10 μM of 15HETE, respectively, as compared with phenylephrine (10 μM) in the presence of NDGA (10 μM). Furthermore, we performed the time‐course analysis of Bcl‐2 protein expression in phenylephrine (10 μM)‐stimulated VSMCs. The expression of Bcl‐2 protein disappeared after a 2 h incubation in the presence of NDGA (10 μM), but remained stable after a 2 h incubation period in the absence of NDGA (10 μM). These results suggest that the lipoxygenase pathway is involved in cell proliferation by preventing apoptosis through the level of Bcl‐2 protein expression.

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Regulation of T-lymphocyte mitogenesis by the leukocyte product 15-hydroxy-eicosatetraenoic acid (15-HETE)

Cited by 106 publications

References 12 publications

Alterations in Epidermal Eicosanoid Metabolism Contribute to Inflammation and Impaired Late Differentiation in FLG-Mutated Atopic Dermatitis

Alterations in Epidermal Eicosanoid Metabolism Contribute to Inflammation and Impaired Late Differentiation in FLG-Mutated Atopic Dermatitis

New Trends in Dual 5-LOX / COX Inhibition

The regulation of mitogenesis and apoptosis in response to the persistent stimulation of α₁‐adrenoceptors: a possible role of 15‐lipoxygenase

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Regulation of T-lymphocyte mitogenesis by the leukocyte product 15-hydroxy-eicosatetraenoic acid (15-HETE)

Cited by 106 publications

References 12 publications

Alterations in Epidermal Eicosanoid Metabolism Contribute to Inflammation and Impaired Late Differentiation in FLG-Mutated Atopic Dermatitis

Alterations in Epidermal Eicosanoid Metabolism Contribute to Inflammation and Impaired Late Differentiation in FLG-Mutated Atopic Dermatitis

New Trends in Dual 5-LOX / COX Inhibition

The regulation of mitogenesis and apoptosis in response to the persistent stimulation of α1‐adrenoceptors: a possible role of 15‐lipoxygenase

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The regulation of mitogenesis and apoptosis in response to the persistent stimulation of α₁‐adrenoceptors: a possible role of 15‐lipoxygenase