scholarly journals Establishment of an Intradermal Ear Injection Model of IL-17A and IL-36γ as a Tool to Investigate the Psoriatic Cytokine Network

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 846
Author(s):  
David Kluwig ◽  
Sebastian Huth ◽  
Ali T. Abdallah ◽  
Carolina M. Pfaff ◽  
Katharina Fietkau ◽  
...  

Psoriasis is a chronic skin disease affecting 2–3% of the global population. The proinflammatory IL-17A is a key cytokine in psoriasis. Accumulating evidence has revealed that IL-36γ plays also a pathogenic role. To understand more precisely the role of the IL-17A–IL-36γ cytokine network in skin pathology, we used an ear injection model. We injected IL-17A or IL-36γ alone and in combination into the ear pinnae of mice. This resulted in a significant increase in ear thickness measured over time. Histological evaluation of IL-17A + IL-36γ-treated skin showed a strong acanthosis, hyperparakeratosis and infiltration of neutrophils. The same histological features were found in mice after injection of IL-36γ alone, but to a lesser extent. IL-17A alone was not able to induce psoriasis-like changes. Genes encoding proteins of the S100 family, antimicrobial peptides and chemo-attractants for neutrophils were upregulated in the IL-17A + IL-36γ group. A much weaker expression was seen after the injection of each cytokine alone. These results strengthen the hypothesis that IL-17A and IL-36γ drive psoriatic inflammation via a synergistic interaction. Our established intradermal ear injection model can be utilized in the future to monitor effects of various inhibitors of this cytokine network.

Author(s):  
Suna Asilsoy ◽  
Serdar Al

Atopic dermatitis (AD) is a chronic skin disease caused by genetic and environmental factors. Often it begins in early childhood. It is located at the first step of the process we refer to as atopic march. This feature is a precursor of the development of other allergic diseases such as asthma and allergic rhinitis. Especially in patients with atopy of food and inhalant allergens, the occurrence of other atopic diseases is more common. Although the role of these sensitivities in AD is controversial, it has been determined that some patients may trigger eczematous skin lesions. In this report, the role of allergens in atopic dermatitis are reviewed in the light of current literature.


2019 ◽  
Vol 14 (1) ◽  
pp. 36-48 ◽  
Author(s):  
Javed Ahmad ◽  
Anuj Gautam ◽  
Shahadali Komath ◽  
Mehdiya Bano ◽  
Anuj Garg ◽  
...  

Background: Acne vulgaris is a common chronic skin disease that affects around 9.4% (approx. 650 million people) of the global population. Growing research in the field of nanomedicine over the years has now been exploited in management of various human disorders. The nanomedicine concept has an immense opportunity for the effective management and control of acne disease by designing a novel, low-dose topical delivery system. Topical nanoemulsion-based gel preparations are said to have various benefits over the conventional formulations. The recent patents on topical anti-acne formulation (US 7241456B2; US 6897238B2; US 6284234B1) provided the concept to design thymol loaded nano-emulgel for topical application in acne. Methods: The objective of the current investigation was to design a thymol loaded nanoemulgel preparation by exploiting low-energy emulsification method for topical application in acne. Furthermore, developed formulation was characterized for thermodynamic stability, mean droplet size, zeta potential, drug content and in-vitro drug diffusion study. Results: The optimized thymol loaded nanoemulsion was found to be 13.60±0.117 nm with PdI 0.197±0.008. Nanoemulsions will provide an enormous surface area for better penetration of therapeutic agent into the pilosebaceous region, resulting better efficacy. Conclusion: From the above studies, it concluded that aqueous-based gel vehicle of the developed formulation system exploited for topical delivery has moisturising properties which can improve local tolerability also.


2011 ◽  
Vol 79 (10) ◽  
pp. 4201-4209 ◽  
Author(s):  
Julia Bugrysheva ◽  
Barbara J. Froehlich ◽  
Jeffrey A. Freiberg ◽  
June R. Scott

ABSTRACTGenes encoding one or more Ser/Thr protein kinases have been identified recently in many bacteria, including one (stk) in the human pathogenStreptococcus pyogenes(group A streptococcus [GAS]). We report that in GAS,stkis required to produce disease in a murine myositis model of infection. Using microarray and quantitative reverse transcription-PCR (qRT-PCR) studies, we found that Stk activates genes for virulence factors, osmoregulation, metabolism of α-glucans, and fatty acid biosynthesis, as well as genes affecting cell wall synthesis. Confirming these transcription studies, we determined that thestkdeletion mutant is more sensitive to osmotic stress and to penicillin than the wild type. We discuss several possible Stk phosphorylation targets that might explain Stk regulation of expression of specific operons and the possible role of Stk in resuscitation from quiescence.


2021 ◽  
pp. 24-28
Author(s):  
A. R. Nazarenko ◽  
N. N. Potekaev ◽  
A. N. Lvov ◽  
N. L. Klyachko ◽  
A. G. Majouga

Modern therapeutic views on the pathogenesis of acne indicate the role of permanent inflammation and expand the arsenal of medicines and combined techniques necessary for the successful treatment of this chronic skin disease. The complex process of immune inflammation in acne with the participation of pro-inflammatory cytokines is due to the interaction of trigger factors and factors of innate immunity. It was found that C. acne is able to interact with markers of increased immunity, such as Toll-like and protease-activated receptors. Based on a detailed analysis of the literature in search systems like PubMed, eLibrary.ru, CyberLeninka, it was found that one of the key roles in inflammation in acne belongs to matrix metalloproteinases. Thus, C. acnes are involved in many processes in the pathogenesis of acne, including inflammation, hyperkeratosis and hyperproduction of sebum, which necessitates its eradication and is an important component of complex therapy. Minocycline (Minolexin) is a highly effective drug for the treatment of moderate to severe forms of acne, including a low-dose regimen, and is included in the European Treatment Guidelines. Minocycline is considered the most powerful inhibitor of MMP, has a pronounced anti-inflammatory effect and a high level of lipophilicity, quickly penetrates the lipid layer of the bacterium and intensively accumulates in the sebaceous glands.


2014 ◽  
Vol 19 (33) ◽  
Author(s):  
K Paranthaman ◽  
A Bentley ◽  
L M Milne ◽  
A Kearns ◽  
S Loader ◽  
...  

Staphylococcal scalded skin syndrome (SSSS) is a blistering skin condition caused by exfoliative toxin-producing strains of Staphylococcus aureus. Outbreaks of SSSS in maternity settings are rarely reported. We describe an outbreak of SSSS that occurred among neonates born at a maternity unit in England during December 2012 to March 2013. Detailed epidemiological and microbiological investigations were undertaken. Eight neonates were found to be infected with the outbreak strain of S. aureus, of spa type t346, representing a single pulsotype. All eight isolates contained genes encoding exfoliative toxin A (eta) and six of them contained genes encoding toxin B (etb). Nasal swabs taken during targeted staff screening yielded a staphylococcal carriage rate of 21% (17/80), but none contained the outbreak strain. Mass screening involving multi-site swabbing and pooled, enrichment culture identified a healthcare worker (HCW) with the outbreak strain. This HCW was known to have a chronic skin condition and their initial nasal screen was negative. The outbreak ended when they were excluded from work. This outbreak highlights the need for implementing robust swabbing and culture methods when conventional techniques are unsuccessful in identifying staff carrier(s). This study adds to the growing body of evidence on the role of HCWs in nosocomial transmission of S. aureus.


Author(s):  
S. Trachtenberg ◽  
P.M. Steinert ◽  
B.L. Trus ◽  
A.C. Steven

During terminal differentiation of vertebrate epidermis, certain specific keratin intermediate filament (KIF) proteins are produced. Keratinization of the epidermis involves cell death and disruption of the cytoplasm, leaving a network of KIF embedded in an amorphous matrix which forms the outer horny layer known as the stratum corneum. Eventually these cells are shed (desquamation). Normally, the processes of differentiation, keratinization, and desquamation are regulated in an orderly manner. In psoriasis, a chronic skin disease, a hyperkeratotic stratum corneum is produced, resulting in abnormal desquamation of unusually large scales. In this disease, the normal KIF proteins are diminished in amount or absent, and other proteins more typical of proliferative epidermal cells are present. There is also evidence of proteolytic degradation of the KIF.


2019 ◽  
Vol 63 (6) ◽  
pp. 757-771 ◽  
Author(s):  
Claire Francastel ◽  
Frédérique Magdinier

Abstract Despite the tremendous progress made in recent years in assembling the human genome, tandemly repeated DNA elements remain poorly characterized. These sequences account for the vast majority of methylated sites in the human genome and their methylated state is necessary for this repetitive DNA to function properly and to maintain genome integrity. Furthermore, recent advances highlight the emerging role of these sequences in regulating the functions of the human genome and its variability during evolution, among individuals, or in disease susceptibility. In addition, a number of inherited rare diseases are directly linked to the alteration of some of these repetitive DNA sequences, either through changes in the organization or size of the tandem repeat arrays or through mutations in genes encoding chromatin modifiers involved in the epigenetic regulation of these elements. Although largely overlooked so far in the functional annotation of the human genome, satellite elements play key roles in its architectural and topological organization. This includes functions as boundary elements delimitating functional domains or assembly of repressive nuclear compartments, with local or distal impact on gene expression. Thus, the consideration of satellite repeats organization and their associated epigenetic landmarks, including DNA methylation (DNAme), will become unavoidable in the near future to fully decipher human phenotypes and associated diseases.


2017 ◽  
pp. 66-71
Author(s):  
O. Yablon ◽  
◽  
N. Zaichko ◽  
O. Mazulov ◽  
Z.I. Rossokha ◽  
...  

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