Cathepsin S, a new pruritus biomarker in clinical dandruff/seborrhoeic dermatitis evaluation

Viodé, Cécile; Lejeune, O.; Turlier, Virginie; Rouquier, Amandine; Casas, Christiane; Mengeaud, V.; Redoulès, Daniel; Schmitt, Anne-Marie

doi:10.1111/exd.12357

Cited by 22 publications

(18 citation statements)

References 10 publications

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“…In the present study, the PgLPS-induced PAR2 activation in the isolated splenic DCs from wild-type mice was completely inhibited in CatS -/- mice ( Figure 5 ), indicating that CatS is involved in PAR2 activation during inflammation (Cattaruzza et al, 2011; Viode et al, 2014). CatS is active at a neutral pH, consistent with its extracellular biological activity (Storm van’s Gravesande et al, 2002), and the PgLPS-induced increase in the IL-6 mRNA expression in splenic DCs from wild-type mice was significantly inhibited by Akti, a specific inhibitor Akt kinase, which is consistent with the findings from previous reports showing CatS-activated PAR2 signaling through the PI3K/Akt pathway in human glioblastoma cells (Dutra-Oliveira et al, 2012).…”

Section: Discussionsupporting

confidence: 53%

“…We next focused on the PAR2 activation and signaling pathways after exposure to PgLPS using the isolated CD11c + DCs, because the CatS-cleaved PAR2 activation is related to the IL-6 expression (Cattaruzza et al, 2011; Viode et al, 2014). The immunoreactivities for PAR2 were significantly higher in the CD11c + DCs from wild-type mice than in the non-PgLPS-exposed isolated CD11c + DCs, but not in those from CatS -/- mice, after exposure to PgLPS for 24 h ( Figures 4B,C ).…”

Section: Resultsmentioning

confidence: 99%

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Cathepsin S Is Involved in Th17 Differentiation Through the Upregulation of IL-6 by Activating PAR-2 after Systemic Exposure to Lipopolysaccharide from Porphyromonas gingivalis

Dekita

et al. 2017

Front. Pharmacol.

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Positive links have been found between periodontitis and numerous diseases in humans via persistent inflammation throughout the body. However, the main factors responsible for maintaining this pro-inflammatory condition are poorly understood. The spleen, the largest secondary immune organ, is a central hub regulating the immune response/inflammation due to the dendritic cell (DC) response to CD4+ T cell subtype differentiation, and lysosomal proteinase cathepsin S (CatS) is known to be involved in DC functions. In the present study, we found that CatS-induced IL-6 production by splenic DCs subsequently promotes Th17 differentiation, in response to systemic exposure to lipopolysaccharide derived from Porphyromonas gingivalis (PgLPS). The population of CD11c+ DCs was significantly increased in the splenic marginal zone (MZ) locally of wild-type (DBA/2) mice with splenomegaly but not in that of CatS deficient (CatS-/-) mice after systemic exposure to PgLPS for 7 consecutive days (5 mg/kg/day, intraperitoneal). Similarly, the population of Th17+CD4+ T cells was also significantly increased in the splenic MZ of wild-type mice but not in that of CatS-/- mice after PgLPS exposure. Furthermore, the increase in the Th17+ CD4+ T cell population paralleled increases in the levels of CatS and IL-6 in CD11c+ cells in the splenic MZ. In isolated primary splenic CD11c+ cells, the mRNA expression and the production of IL-6 was dramatically increased in wild-type mice but not in CatS-/- mice after direct stimulation with PgLPS (1 μg/ml), and this PgLPS-induced increase in the IL-6 expression was completely abolished by pre-treatment with Z-Phe-Leu-COCHO (Z-FL), the specific inhibitor of CatS. The PgLPS activated protease-activated receptor (PAR) 2 in the isolated splenic CD11c+ cells was also significantly inhibited by CatS deficiently. In addition, the PgLPS-induced increase in the IL-6 production by splenic CD11c+ cells was completely abolished by pre-treatment with FSLLRY-NH2, a PAR2 antagonist, as well as Akti, a specific inhibitor of Akt. These findings indicate that CatS plays a critical role in driving splenic DC-dependent Th17 differentiation through the upregulation of IL-6 by activating PAR2 after exposure to components of periodontal bacteria. Therefore, CatS-specific inhibitors may be effective in alleviating periodontitis-related immune/inflammation.

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Section: Discussionsupporting

confidence: 53%

Section: Resultsmentioning

confidence: 99%

Cathepsin S Is Involved in Th17 Differentiation Through the Upregulation of IL-6 by Activating PAR-2 after Systemic Exposure to Lipopolysaccharide from Porphyromonas gingivalis

Dekita

et al. 2017

Front. Pharmacol.

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“…Increased cat S expression has been reported in several common inflammatory skin conditions, including atopic dermatitis, psoriasis and seborrheic dermatitis 18 , 19 , 38 . Under these conditions, cat S may simultaneously contribute to itch and propagate inflammation via different but related mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Redefining the concept of protease-activated receptors: cathepsin S evokes itch via activation of Mrgprs

et al. 2015

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Sensory neurons expressing Mas-related G protein coupled receptors (Mrgprs) mediate histamine-independent itch. We show that the cysteine protease cathepsin S activates MrgprC11 and evokes receptor-dependent scratching in mice. In contrast to its activation of conventional protease-activated receptors, cathepsin S mediated activation of MrgprC11 did not involve the generation of a tethered ligand. We demonstrate further that different cysteine proteases selectively activate specific mouse and human Mrgpr family members. This expansion of our understanding by which proteases interact with GPCRs redefines the concept of what constitutes a protease-activated receptor. The findings also implicate proteases as ligands to members of this orphan receptor family while providing new insights into how cysteine proteases contribute to itch.

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“…Sebaceous glands contribute to skin barrier function and their alteration may play a role in the pathogenesis of seborrheic dermatitis and other common skin diseases such as acne vulgaris, atopic dermatitis, psoriasis, and rosacea [30]. There is a significant increase in the levels of the biological markers cathepsin S, proteinase-activated receptor 2 and histamine patients with seborrheic dermatitis which correlate with clinical parameters [31].…”

Section: Pathogenesis Of Seborrheic Dermatitismentioning

confidence: 99%

New Insights into the Etiopathogenesis of Seborrheic Dermatitis

Argirov¹,

Bakardzhiev²

2017

CRDOA

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Seborrheic dermatitis represents a chronic, widespread skin disease that is considered a multifactorial disorder influenced, in part, by Malassezia spp.opportunistic activities as well as by various endogenous and exogenous factors. This review systematizes the recent scientific achievements in the field of insufficiently elucidated etiology and pathogenesis of seborrheic dermatitis. IntroductionSeborrheic dermatitis is initially described by P. G. Unna in 1887 and the association with Malassezia yeasts is accepted up to the middle of the 20th century, when the observed increased epidermal cell turnover gradually prompts researchers to characterize this condition as being intrinsic to the skin[1, 2].Seborrheic dermatitis is common dermatological problem that affects the seborrheic areas of the body. It is considered the same basic condition like dandruff sharing many features and responding to similar treatments, differing only in locality and severity. Current use of varying terms for seborrheic dermatitis such as sebopsoriasis, seborrheic eczema, dandruff, and pityriasis capitis reflects the complex nature of this common skin pathology [3]. Much controversy remains regarding the pathogenesis of seborrheic dermatitis and its classification in the spectrum of cutaneous diseases as a form of dermatitis, a fungal disease, or an inflammatory disease, closely related with psoriasis.The prevalence of seborrheic dermatitis peaks when sebaceous gland activity is high, during the first three months of life (infantile seborrheic dermatitis), during puberty and when sebum excretion is reduced after the age of 50 years [2]. Because of smaller sebum production, seborrheic dermatitis flares occur more often in spring than in summer. Disease flare could be associated with altered population dynamics affected not only by variations in sebaceous gland activity but also by modifications in other nutrients supplied by sweat, such as essential amino acids like glycine and tryptophan.Glycine stimulates the fast growth of M. furfur and after its exhaustion yeast cells employ tryptophan as a nitrogen source, increasing the production of indolic metabolites [4]. Such cycles of population growth, bioactive indole production, and subsequent deprivation of nutrients result in insufficiently masked antigens and ligands on the surface of the yeast cells leading to immune system activation.Seborrheic dermatitis occurs on the scalp as well as on face, retroauricular area, and the upper chest, causing flaking, scaling, inflammation, pruritus, and, sometimes, marked erythema [5]. Flaking is usually white-to-yellowish, and may be oily or dry. Various intrinsic and environmental factors, such as sebaceous secretions, skin surface fungal colonization, individual susceptibility, and interactions between these factors play a pathogenetic role in seborrheic dermatitis. Etiology of Seborrheic DermatitisThere are three principal factors that play a role in the etiology of seborrheic dermatitis [6]: sebaceous gland secretion, alteration in col...

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Cathepsin S, a new pruritus biomarker in clinical dandruff/seborrhoeic dermatitis evaluation

Cited by 22 publications

References 10 publications

Cathepsin S Is Involved in Th17 Differentiation Through the Upregulation of IL-6 by Activating PAR-2 after Systemic Exposure to Lipopolysaccharide from Porphyromonas gingivalis

Cathepsin S Is Involved in Th17 Differentiation Through the Upregulation of IL-6 by Activating PAR-2 after Systemic Exposure to Lipopolysaccharide from Porphyromonas gingivalis

Redefining the concept of protease-activated receptors: cathepsin S evokes itch via activation of Mrgprs

New Insights into the Etiopathogenesis of Seborrheic Dermatitis

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