Phospholipase A
            <sub>2</sub>
            Inhibition as Potential Therapy for Inflammatory Skin Diseases

Mruwat, Rufayda; Cohen, Yuval; Yedgar, Saul

doi:10.2217/imt.13.18

Cited by 13 publications

(8 citation statements)

References 18 publications

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“…cPLA2 is an enzyme which hydrolyzes phospholipids to produce arachidonic acid or lysophospholipids and is also a type of inflammatory factor. Notably, cPLA2 inhibitors may be potential therapeutic agents for inflammatory skin diseases [67,68]. Our results revealed that glycofullerenes could inhibit the expression of COX-2, HO-1, MMP-9, ICAM-1, and cPLA2, as well as the production of PGE2, induced by PM treatment, while C 60 -H 2 O did not ( Figure 6).…”

Section: Discussionmentioning

confidence: 75%

Glycofullerenes Inhibit Particulate Matter Induced Inflammation and Loss of Barrier Proteins in HaCaT Human Keratinocytes

Lee

Chiang

et al. 2020

Biomolecules

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Exposure to particulate matter (PM) has been linked to pulmonary and cardiovascular dysfunctions, as well as skin diseases, etc. PM impairs the skin barrier functions and is also involved in the initiation or exacerbation of skin inflammation, which is linked to the activation of reactive oxygen species (ROS) pathways. Fullerene is a single C60 molecule which has been reported to act as a good radical scavenger. However, its poor water solubility limits its biological applications. The glyco-modification of fullerenes increases their water solubility and anti-bacterial and anti-virus functions. However, it is still unclear whether it affects their anti-inflammatory function against PM-induced skin diseases. Hence, glycofullerenes were synthesized to investigate their effects on PM-exposed HaCaT human keratinocytes. Our results showed that glycofullerenes could reduce the rate of PM-induced apoptosis and ROS production, as well as decrease the expression of downstream mitogen-activated protein kinase and Akt pathways. Moreover, PM-induced increases in inflammatory-related signals, such as cyclooxygenase-2, heme oxygenase-1, and prostaglandin E2, were also suppressed by glycofullerenes. Notably, our results suggested that PM-induced impairment of skin barrier proteins, such as filaggrin, involucrin, repetin, and loricrin, could be reduced by pre-treatment with glycofullerenes. The results of this study indicate that glycofullerenes could be potential candidates for treatments against PM-induced skin diseases and that they exert their protective effects via ROS scavenging, anti-inflammation, and maintenance of the expression of barrier proteins.

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Section: Discussionmentioning

confidence: 75%

Glycofullerenes Inhibit Particulate Matter Induced Inflammation and Loss of Barrier Proteins in HaCaT Human Keratinocytes

Lee

Chiang

et al. 2020

Biomolecules

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“…5,6 EETs have been shown to increase endothelial cell migration and capillary tube formation 56 which could explain why we see more blood vessel sprouts in the LIGHT 2/2 mice than in the control Application of cys-LTD 4 in human skin has been shown to cause infiltration of neutrophils. 57 This LT can be secreted by macrophages, which are increased in LIGHT 2/2 wounds, 16 and prompt b-catenin translocation to the nucleus and activation of the target genes c-myc and cyclin D1. 58 Significant increase of expression of the latter two genes has been shown to be present in the nonhealing wound edge of chronic ulcers and to inhibit epithelialization.…”

Section: Discussionmentioning

confidence: 99%

“…Application of cys‐LTD 4 in human skin has been shown to cause infiltration of neutrophils . This LT can be secreted by macrophages, which are increased in LIGHT −/− wounds, and prompt β‐catenin translocation to the nucleus and activation of the target genes c‐myc and cyclin D1 . Significant increase of expression of the latter two genes has been shown to be present in the nonhealing wound edge of chronic ulcers and to inhibit epithelialization .…”

Section: Discussionmentioning

confidence: 99%

“…It can be released from the membrane by activation of receptors that turn on phospholipase A2 which, in turn, hydrolyzes the sn‐2 ester bond in the phospholipid, releasing AA as a free fatty acid . The release of AA initiates a cascade of events resulting in the generation of numerous lipid mediators that trigger inflammation, increased vascular permeability and platelet activation . These mediators can be generated either via nonenzymatic or enzymatic pathways.…”

mentioning

confidence: 99%

“…14 The release of AA initiates a cascade of events resulting in the generation of numerous lipid mediators that trigger inflammation, increased vascular permeability and platelet activation. 15,16 These mediators can be generated either via nonenzymatic or enzymatic pathways. The nonenzymatic pathway involves free radicals generated when there is excess oxidative stress that causes the production of isoprostanes.…”

mentioning

confidence: 99%

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Arachidonic acid‐derived signaling lipids and functions in impaired healing

Dhall

Wijesinghe

Karim

et al. 2015

Wound Repair Regeneration

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Very little is known about lipid function during wound healing, and much less during impaired healing. Such understanding will help identify what roles lipid signaling plays in the development of impaired/chronic wounds. We took a lipidomics approach to study the alterations in lipid profile in the LIGHT−/− mouse model of impaired healing which has characteristics that resemble those of impaired/chronic wounds in humans, including high levels of oxidative stress, excess inflammation, increased extracellular matrix degradation and blood vessels with fibrin cuffs. The latter suggests excess coagulation and potentially increased platelet aggregation. We show here that in these impaired wounds there is an imbalance in the arachidonic acid (AA) derived eicosonoids that mediate or modulate inflammatory reactions and platelet aggregation. In the LIGHT−/− impaired wounds there is a significant increase in enzymatically derived breakdown products of AA. We found that early after injury there was a significant increase in the eicosanoids 11-, 12-, and 15-hydroxyeicosa-tetranoic acid, and the proinflammatory leukotrienes (LTD4 and LTE) and prostaglandins (PGE2 and PGF2α). Some of these eicosanoids also promote platelet aggregation. This led us to examine the levels of other eicosanoids known to be involved in the latter process. We found that thromboxane (TXA2/B2), and prostacyclins 6kPGF1α are elevated shortly after wounding and in some cases during healing. To determine whether they have an impact in platelet aggregation and hemostasis, we tested LIGHT−/− mouse wounds for these two parameters and found that, indeed, platelet aggregation and hemostasis are enhanced in these mice when compared with the control C57BL/6 mice. Understanding lipid signaling in impaired wounds can potentially lead to development of new therapeutics or in using existing nonsteroidal anti-inflammatory agents to help correct the course of healing.

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Metabolomic and lipidomic fingerprints in inflammatory skin diseases – Systemic illumination of atopic dermatitis, hidradenitis suppurativa and plaque psoriasis

Rischke,

Schäfer,

König

et al. 2024

Clinical Immunology

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Phospholipase A ₂ Inhibition as Potential Therapy for Inflammatory Skin Diseases

Cited by 13 publications

References 18 publications

Glycofullerenes Inhibit Particulate Matter Induced Inflammation and Loss of Barrier Proteins in HaCaT Human Keratinocytes

Glycofullerenes Inhibit Particulate Matter Induced Inflammation and Loss of Barrier Proteins in HaCaT Human Keratinocytes

Arachidonic acid‐derived signaling lipids and functions in impaired healing

Metabolomic and lipidomic fingerprints in inflammatory skin diseases – Systemic illumination of atopic dermatitis, hidradenitis suppurativa and plaque psoriasis

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Phospholipase A 2 Inhibition as Potential Therapy for Inflammatory Skin Diseases

Cited by 13 publications

References 18 publications

Glycofullerenes Inhibit Particulate Matter Induced Inflammation and Loss of Barrier Proteins in HaCaT Human Keratinocytes

Glycofullerenes Inhibit Particulate Matter Induced Inflammation and Loss of Barrier Proteins in HaCaT Human Keratinocytes

Arachidonic acid‐derived signaling lipids and functions in impaired healing

Metabolomic and lipidomic fingerprints in inflammatory skin diseases – Systemic illumination of atopic dermatitis, hidradenitis suppurativa and plaque psoriasis

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Phospholipase A ₂ Inhibition as Potential Therapy for Inflammatory Skin Diseases