Future treatment options for atopic dermatitis – Small molecules and beyond

Schäkel, Knut; Döbel, Thomas; Bosselmann, Ina

doi:10.1016/j.jdermsci.2013.11.009

Cited by 27 publications

(15 citation statements)

References 79 publications

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“…However, the current principal treatment, topical corticosteroid, can have detrimental effects (e.g., perioral dermatitis and skin atrophy), and individuals becoming refractory to topical application require systemic treatment, with potentially severe adverse effects (Schakel et al., 2014). Development of interventions to restore barrier integrity was recently identified by researchers, clinicians, patients, and policymakers as a top-10 translational dermatology research priority in an e-Delphi exercise (Healy et al., 2015).…”

Section: Discussionmentioning

confidence: 99%

IL-1β–Induced Protection of Keratinocytes against Staphylococcus aureus-Secreted Proteases Is Mediated by Human β-Defensin 2

Wang

McHugh

Qureshi

et al. 2017

Journal of Investigative Dermatology

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Atopic dermatitis (AD) is a common chronic inflammatory skin disease that results in significant morbidity. A hallmark of AD is disruption of the critical barrier function of upper epidermal layers, causatively linked to environmental stimuli, genetics, and infection, and a critical current target for the development of new therapeutic and prophylactic interventions. Staphylococcus aureus is an AD-associated pathogen producing virulence factors that induce skin barrier disruption in vivo and contribute to AD pathogenesis. We show, using immortalized and primary keratinocytes, that S. aureus protease SspA/V8 is the dominant secreted factor (in laboratory and AD clinical strains of S. aureus) inducing barrier integrity impairment and tight junction damage. V8-induced integrity damage was inhibited by an IL-1β–mediated mechanism, independent of effects on claudin-1. Induction of keratinocyte expression of the antimicrobial/host defense peptide human β-defensin 2 (hBD2) was found to be the mechanism underpinning this protective effect. Endogenous hBD2 expression was required and sufficient for protection against V8 protease-mediated integrity damage, and exogenous application of hBD2 was protective. This modulatory property of hBD2, unrelated to antibacterial effects, gives new significance to the defective induction of hBD2 in the barrier-defective skin lesions of AD and indicates therapeutic potential.

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Section: Discussionmentioning

confidence: 99%

IL-1β–Induced Protection of Keratinocytes against Staphylococcus aureus-Secreted Proteases Is Mediated by Human β-Defensin 2

Wang

McHugh

Qureshi

et al. 2017

Journal of Investigative Dermatology

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“…Several cytokines were also measured before and after 8 weeks of intervention, because they had been reported to relate to the pathogenesis of AD [20,21]. …”

Section: Methodsmentioning

confidence: 99%

Effects of Oral Administration of <b><i>Lactobacillus acidophilus </i></b>L-92 on the Symptoms and Serum Cytokines of Atopic Dermatitis in Japanese Adults: A Double-Blind, Randomized, Clinical Trial

Inoue

Kambara

Murata

et al. 2014

Int Arch Allergy Immunol

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Objectives: Several studies on lactobacilli have demonstrated they are effective against atopic dermatitis (AD) in children, but there are very few reports of their effects in adults. We investigated the changes in AD symptoms in adults after the ingestion of the Lactobacillus acidophilus strain L-92 (L-92), which has been shown to have a curative effect on AD in children. Methods: A double-blind, parallel-group, placebo-controlled comparison was performed on 49 AD patients aged ≥16 years using heat-killed L-92. Skin lesions were assessed using the SCORing AD (SCORAD) index before the start of L-92 ingestion and 4 and 8 weeks after ingestion. Serum cytokine and blood marker levels were measured 8 weeks after the start of L-92 ingestion. Results: The group that ingested L-92 had lower SCORAD scores than the controls (p = 0.002). The L-92 group also had decreased ratios of change for eosinophil count (p = 0.03) and increased ratios of change for serum TGF-β (p = 0.03). Ratios of change for serum TGF-β rose significantly (p = 0.04) in patients showing mitigated symptoms with L-92 administration. Conclusions: Administration of heat-killed L-92 was effective for AD symptoms in adults. L-92 may contribute to the suppression of Th2-dominant inflammation. Our preliminary trial is the first to report the effects of L-92 on adult AD.

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“…A number of pharmacological controls for AD involve topical or systemic administration of steroids, antihistamines or specific inhibitors of NF-kB [19]. Steroids reduce all Th cell functions and are widely used as immunosuppressants [20].…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effect of 5,6-dihydroergosteol-glucoside on atopic dermatitis-like skin lesions via suppression of NF-κB and STAT activation.

Jung

Lee

et al. 2015

Journal of Dermatological Science

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Future treatment options for atopic dermatitis – Small molecules and beyond

Cited by 27 publications

References 79 publications

IL-1β–Induced Protection of Keratinocytes against Staphylococcus aureus-Secreted Proteases Is Mediated by Human β-Defensin 2

IL-1β–Induced Protection of Keratinocytes against Staphylococcus aureus-Secreted Proteases Is Mediated by Human β-Defensin 2

Effects of Oral Administration of <b><i>Lactobacillus acidophilus </i></b>L-92 on the Symptoms and Serum Cytokines of Atopic Dermatitis in Japanese Adults: A Double-Blind, Randomized, Clinical Trial

Inhibitory effect of 5,6-dihydroergosteol-glucoside on atopic dermatitis-like skin lesions via suppression of NF-κB and STAT activation.

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