Characterization of Group X Phospholipase A2 as the Major Enzyme Secreted by Human Keratinocytes and its Regulation by the Phorbol Ester TPA

Schadow, Alexia; Scholz‐Pedretti, Kirsten; Lambeau, Gérard; Gelb, Michael H.; Fürstenberger, Gerhard; Pfeilschifter, Josef; Kaszkin, Marietta

doi:10.1046/j.1523-1747.2001.00179.x

Cited by 38 publications

(3 citation statements)

References 59 publications

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“…However, the sPLA 2 -IB inhibitor used in that study, p-bromophenacyl bromide, also alkylates the active site histidine that is conserved in all sPLA 2 s and most likely inhibits multiple sPLA 2 s 53. A more recent study has shown that in filaggrin-deficient ft/ft mice, sPLA 2 -IIA is upregulated along with NHE1 expression, while sPLA 2 forms -IIF and -X do not,1 contrasting with a previous study that demonstrated that sPLA 2 -IIA does not contribute to acidification and barrier function and sPLA 2 s-X is the main isoform to be secreted from keratinocytes 54. To assign more definitive roles to these isoforms, more enzyme-specific sPLA 2 s antibodies and inhibitors are needed, which in part will enable the identification of specific sPLA 2 s present within LB.…”

Section: The Secretory Phospholipase Familymentioning

confidence: 79%

Acidification in the epidermis and the role of secretory phospholipases

Chan

Mauro

2011

Dermato-Endocrinology

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The function of the epidermis is to form an effective barrier between the dry, external environment and the interior of the body. The barrier specifically resides in the extracellular lipid membranes of the stratum corneum (SC) and an acidic pH is necessary to maintain its competency against various insults. The purpose of this review is to explore the mechanisms which are postulated to contribute to the acidification of the stratum corneum, including both exogenous and endogenous sources. However, recent research as pointed to several endogenous mechanisms as the major source of acidification, including a sodium/proton pump (NHE1) and free fatty acid conversion from phospholipids by secretory phospholipase A2 (sPLA2). sPLA2 has been shown to play a central role in the formation of the SC “acid mantle” in the early maturation of the epidermis postnatally. Many aspects of this enzyme family are complex and still being elucidated in research and the most recent findings on the localization and functions of sPL A2-IB, -IIA, -IIC, -IID, -IIE, -IIF, -III, -V, -X and -XII in the epidermis are presented here. Given their role in inflammatory dermatoses, such as psoriasis and atopic dermatitis, understanding this complex enzyme family can lead to novel, life-changing therapies.

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Section: The Secretory Phospholipase Familymentioning

confidence: 79%

Acidification in the epidermis and the role of secretory phospholipases

Chan

Mauro

2011

Dermato-Endocrinology

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“…The sPLA 2 family consists of 11 isoforms with distinct substrate specificities and tissue distributions [17,18]. Historically, several sPLA 2 s have been detected in mouse and human skin, but by using semi-quantitative RT-PCR and immunoblotting which have uncertain specificity [19][20][21][22][23]. sPLA 2 s have also been suggested to supply fatty acids for formation of the SC acid mantle, a hypothesis that stems primarily from the observation that SC acidity is perturbed by non-specific sPLA 2 inhibitors [15,[23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Phospholipase A2 in skin biology: new insights from gene-manipulated mice and lipidomics

2018

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The skin represents one of the tissues that are most profoundly influenced by alterations in the quality of lipids (lipoquality). Lipids not only constitute cellular membranes, but also serve as bioactive lipid mediators and essential components of the skin barrier. Phospholipase A2 (PLA2) enzymes supply fatty acids and lysophospholipids from membrane phospholipids, thereby variably affecting cutaneous homeostasis. Accordingly, perturbation of particular PLA2-driven lipid pathways can be linked to various forms of skin disease. In this review article, we highlight the roles of several PLA2 subtypes in cutaneous pathophysiology, as revealed by transgenic/knockout studies in combination with comprehensive lipidomics. We focus mainly on secreted PLA2 group IIF (sPLA2-IIF), which is associated with epidermal hyperplasia through mobilization of a unique lipid metabolite. We also address the distinct roles of sPLA2-IIE in hair follicles and sPLA2-IID in lymphoid immune cells that secondarily affect cutaneous inflammation, and provide some insights into species differences in sPLA2s. Additionally, we briefly overview the patatin-like phospholipase PNPLA1, which belongs to the Ca2+-independent PLA2 (iPLA2) family, as a key regulator of skin barrier function through catalysis of a unique non-PLA2 reaction. These knowledges on lipid metabolism driven by various PLA2 subtypes will open novel opportunities for translated studies toward diagnosis and therapy of human skin diseases.

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“…A nivel histológico, se produce la etapa vascular y la etapa celular. A nivel bioquímico, se eleva la síntesis del ácidos nucleicos, los cuales activan los genes de expresión de los mediadores de la inflamación, como son IL-6, IL-10 y TNF-α (Schadow et al, 2001).…”

Section: Edema Auricular Inducido Por 13-acetato De 12-o-tetradecanoi...unclassified

Estudio químico y evaluación de la actividad antiinflamatoria de los extractos orgánicos de Senna crotalarioides Kunth

Serrano Vega

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Characterization of Group X Phospholipase A2 as the Major Enzyme Secreted by Human Keratinocytes and its Regulation by the Phorbol Ester TPA

Abstract: Pyr-1, 3-(2,6-dichlorophenylsulfonylamino)-4-(2-(4-acetamido)pyridyl)-5-(3-(4-¯uorophenoxy)benzyl(thio)-(1H)-pyrazole; sPLA 2 , secreted phospholipase A 2 .

Cited by 38 publications

References 59 publications

Acidification in the epidermis and the role of secretory phospholipases

Acidification in the epidermis and the role of secretory phospholipases

Phospholipase A2 in skin biology: new insights from gene-manipulated mice and lipidomics

Estudio químico y evaluación de la actividad antiinflamatoria de los extractos orgánicos de Senna crotalarioides Kunth

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