Self‐maintenance of neurogenic inflammation contributes to a vicious cycle in skin

Gouin, Olivier; Lebonvallet, Nicolas; L’Hérondelle, Killian; Buhé, Virginie; Plée-Gautier, Emmanuelle; Carré, Jean‐Luc; Lefeuvre, Luc; Miséry, Laurent

doi:10.1111/exd.12798

Cited by 37 publications

(38 citation statements)

References 71 publications

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“…On an in vitro reconstructed a model of the differentiated human epidermis, an increased mortality with creams containing LA at similar concentrations to our observed cytotoxic effect was previously shown . SP release is correlated with CNI and is regularly used as a neuro‐inflammatory marker . We assumed that LA possesses a pro‐inflammatory effect on the cells.…”

Section: Discussionsupporting

confidence: 80%

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A new tool to test active ingredient using lactic acid in vitro, a help to understand cellular mechanism involved in stinging test: An example using a bacterial polysaccharide (Fucogel^®)

Sakka

Leschiera

Gouin

et al. 2018

Experimental Dermatology

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The stinging test is an in vivo protocol that evaluates sensitive skin using lactic acid (LA). A soothing sensation of cosmetics or ingredients can be also appreciated through a decrease in stinging score. To predict the soothing sensation of a product before in vivo testing, we developed a model based on an LA test and substance P (SP) release using a co-culture of human keratinocytes and NGF-differentiated PC12 cells. A bacterial fucose-rich polysaccharide present in Fucogel was evaluated as the soothing molecule in the in vivo stinging test and our in vitro model. Excluding toxic concentrations, the release of SP was significant from 0.2% of lactic acid for the PC12 cells and from 0.1% of lactic acid for the keratinocytes. When the pH was adjusted to approximately 7.4, LA did not provoke SP release. At these concentrations of LA, 0.1% of polysaccharide showed a significant decrease in SP release from the two cellular types and in co-cultures without modifying the pH of the medium. In vivo, a stinging test using the polysaccharide showed a 30% decrease in prickling intensity vs the placebo in 19 women between the ages of 21 and 69. Our in vitro model is ethically interesting and is adapted for cosmetic ingredients screening because it does not use animal experimentation and limits human volunteers. Moreover, Fucogel reduced prickling sensation as revealed by the in vivo stinging test and inhibits the neurogenic inflammation as showed by our new in vitro stinging test based on SP release.

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Section: Discussionsupporting

confidence: 80%

“…Moreover, protons at a pH less than 5.9 activate TRPV1. The activation of TRPV1 increases intracellular calcium and participates in SP release and CNI . The receptors activated by the ligand lactic acid are hydroxycarboxylic acid receptors (HCA).…”

Section: Discussionmentioning

confidence: 99%

A new tool to test active ingredient using lactic acid in vitro, a help to understand cellular mechanism involved in stinging test: An example using a bacterial polysaccharide (Fucogel^®)

Sakka

Leschiera

Gouin

et al. 2018

Experimental Dermatology

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“…Cutaneous neurogenic inflammation is inflammation that is induced in the skin by the release of neuropeptides such as substance P and calcitonin gene‐related peptide from sensory nerve endings, which leads to mainly sensory and vascular disorders such as pruritus, erythema and oedema . TRPV1 is a nonselective cation channel known to participate specifically in pain and cutaneous neurogenic inflammation .…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety ofPAC‐14028 cream – a novel, topical, nonsteroidal, selectiveTRPV1 antagonist in patients with mild‐to‐moderate atopic dermatitis: a phaseIIb randomized trial

et al. 2019

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SummaryBackgroundTransient receptor potential vanilloid subfamily, member 1 (TRPV1) may play an important role in pruritus and inflammation induction in atopic dermatitis (AD). The treatment effect of TRPV1 antagonist via topical application in patients with AD remains unknown.ObjectivesTo assess the clinical efficacy and safety of PAC‐14028, a TRPV1 antagonist, via topical application in patients with AD.MethodsIn this 8‐week, phase IIb, randomized, double‐blind, multicentre, vehicle‐controlled study, patients with mild‐to‐moderate AD were randomized to receive PAC‐14028 cream 0·1%, 0·3%, 1·0% or vehicle cream twice daily. The primary efficacy end point was the Investigator's Global Assessment (IGA) success rate defined as the percentage of patients with an IGA score of 0 or 1 at week 8. The secondary efficacy end points included the severity Scoring of Atopic Dermatitis (SCORAD) index and Eczema Area and Severity Index (EASI) 75/90.ResultsA total of 194 patients were enrolled. IGA success rates at week 8 were 14·58% for vehicle cream, 42·55% for PAC‐14028 cream 0·1% (P = 0·0025 vs. vehicle), 38·30% for PAC‐14028 cream 0·3% (P = 0·0087 vs. vehicle) and 57·45% for PAC‐14028 cream 1·0% (P < 0·001 vs. vehicle). In particular, statistically significant differences were found between the vehicle and treatment groups in the IGA success rates with two‐grade improvement. The SCORAD index, EASI 75/90, sleep disturbance score and pruritus visual analogue scale showed a trend towards improvement. No significant safety issues were reported.Conclusions PAC‐14028 cream may be an effective and safe treatment modality for the treatment of patients with mild‐to‐moderate AD.

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“…In psoriasis, HAT might be associated with wound repair and hyperproliferation via EGFR signaling (133) and might promote IL-8 production and the accumulation of neutrophils into the epidermis (104), mediated through the activation of PAR-2. A proinflammatory role of PAR-2 during cutaneous inflammation has already been demonstrated, in humans as well as in mice (59,129), and the receptor has also been associated with atopic dermatitis (130), rosacea (64), cutaneous neurogenic inflammation (CNI) (41), and the Netherton syndrome (22), which may also be HATmediated.…”

Section: L661mentioning

confidence: 99%

Human airway trypsin-like protease, a serine protease involved in respiratory diseases

Menou

Duitman

Flajolet

et al. 2017

American Journal of Physiology-Lung Cellular and Molecular Phys

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More than 2% of all human genes are coding for a complex system of more than 700 proteases and protease inhibitors. Among them, serine proteases play extraordinary, diverse functions in different physiological and pathological processes. The human airway trypsin-like protease (HAT), also referred to as TMPRSS11D and serine 11D, belongs to the emerging family of cell surface proteolytic enzymes, the type II transmembrane serine proteases (TTSPs). Through the cleavage of its four major identified substrates, HAT triggers specific responses, notably in epithelial cells, within the pericellular and extracellular environment, including notably inflammatory cytokine production, inflammatory cell recruitment, or anticoagulant processes. This review summarizes the potential role of this recently described protease in mediating cell surface proteolytic events, to highlight the structural features, proteolytic activity, and regulation, including the expression profile of HAT, and discuss its possible roles in respiratory physiology and disease.

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Self‐maintenance of neurogenic inflammation contributes to a vicious cycle in skin

Cited by 37 publications

References 71 publications

A new tool to test active ingredient using lactic acid in vitro, a help to understand cellular mechanism involved in stinging test: An example using a bacterial polysaccharide (Fucogel^®)

A new tool to test active ingredient using lactic acid in vitro, a help to understand cellular mechanism involved in stinging test: An example using a bacterial polysaccharide (Fucogel^®)

Efficacy and safety ofPAC‐14028 cream – a novel, topical, nonsteroidal, selectiveTRPV1 antagonist in patients with mild‐to‐moderate atopic dermatitis: a phaseIIb randomized trial

Human airway trypsin-like protease, a serine protease involved in respiratory diseases

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Self‐maintenance of neurogenic inflammation contributes to a vicious cycle in skin

Cited by 37 publications

References 71 publications

A new tool to test active ingredient using lactic acid in vitro, a help to understand cellular mechanism involved in stinging test: An example using a bacterial polysaccharide (Fucogel®)

A new tool to test active ingredient using lactic acid in vitro, a help to understand cellular mechanism involved in stinging test: An example using a bacterial polysaccharide (Fucogel®)

Efficacy and safety ofPAC‐14028 cream – a novel, topical, nonsteroidal, selectiveTRPV1 antagonist in patients with mild‐to‐moderate atopic dermatitis: a phaseIIb randomized trial

Human airway trypsin-like protease, a serine protease involved in respiratory diseases

Contact Info

Product

Resources

About

A new tool to test active ingredient using lactic acid in vitro, a help to understand cellular mechanism involved in stinging test: An example using a bacterial polysaccharide (Fucogel^®)

A new tool to test active ingredient using lactic acid in vitro, a help to understand cellular mechanism involved in stinging test: An example using a bacterial polysaccharide (Fucogel^®)