scholarly journals Comparison of the Inhibitory Activities of 5,6-Dihydroergosterol Glycoside α- and β-Anomers on Skin Inflammation

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 371 ◽  
Author(s):  
Tae Kim ◽  
Young Cho ◽  
HoonGyu Park ◽  
Tae Lee ◽  
Hakwon Kim

Chronic skin inflammatory diseases, such as atopic dermatitis, are associated with a dysfunctional skin barrier due to an increase in various inflammatory stimuli, for instance inflammatory cytokines and chemokines. In particular, CCL17 and CCL22 expression is increased in patients with chronic skin inflammation. In this study, we synthesized several α- and β-anomers of dihydroergosterol (DHE)-glycosides and assessed their effects on CCL17 and CCL22 expression. We confirmed that the β-anomers of DHE-glycosides were superior to α-anomers of DHE-glycosides in inhibiting CCL17 and CCL22 mRNA and protein expression. In addition, we determined that DHE-glycoside β-anomers showed strong inhibitory activity towards pro-inflammatory cytokine mRNA and protein expression, including that of TNF-α, IL-6, and IL-1β- in stimulated HaCaT cells. These results imply that DHE-glycoside α- and β-anomers should be separated during synthesis of drugs for chronic skin inflammation. Our results also suggest that β-anomers of DHE-glycosides may play an important role as new drugs for chronic skin inflammation because of their ability to inhibit the skin inflammatory biomarker proteins CCL17 and CCL22.

2012 ◽  
Vol 87 (5) ◽  
pp. 729-734 ◽  
Author(s):  
Vanessa Petry ◽  
Giancarlo Resende Bessa ◽  
Claudia Schermann Poziomczyck ◽  
Caio Fernando de Oliveira ◽  
Magda Blessmann Weber ◽  
...  

Atopic Dermatitis is a chronic inflammatory skin disease that affects a large number of children and adults. The disease results from an interaction between genetic predisposition, host environment, skin barrier defects, and immunological factors. A major aggravating factor associated with Atopic Dermatitis is the presence of microorganisms on the patient's skin surface. Staphylococcus aureus and Streptococcus pyogenes, for instance, can exacerbate chronic skin inflammation. As a result, antimicrobials have often been prescribed to control the acute phase of the disease. However, increased bacterial resistance to antimicrobial agents has made it difficult for dermatologists to prescribe appropriate medication. In the presence of disseminated dermatitis with secondary infection, systemic antibiotics need to be prescribed; however, treatment should be individualized, in an attempt to find the most effective antibiotic with fewer side effects. Also, the medication should be used for as short as possible in order to minimize bacterial resistance.


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Silvana Zgraggen ◽  
Alexandra M. Ochsenbein ◽  
Michael Detmar

Angiogenesis and lymphangiogenesis, the growth of new vessels from preexisting ones, have received increasing interest due to their role in tumor growth and metastatic spread. However, vascular remodeling, associated with vascular hyperpermeability, is also a key feature of many chronic inflammatory diseases including asthma, atopic dermatitis, psoriasis, and rheumatoid arthritis. The major drivers of angiogenesis and lymphangiogenesis are vascular endothelial growth factor- (VEGF-)A and VEGF-C, activating specific VEGF receptors on the lymphatic and blood vascular endothelium. Recent experimental studies found potent anti-inflammatory responses after targeted inhibition of activated blood vessels in models of chronic inflammatory diseases. Importantly, our recent results indicate that specific activation of lymphatic vessels reduces both acute and chronic skin inflammation. Thus, antiangiogenic and prolymphangiogenic therapies might represent a new approach to treat chronic inflammatory disorders, including those due to chronic allergic inflammation.


2021 ◽  
Vol 22 (9) ◽  
pp. 4589
Author(s):  
Martin Voss ◽  
Johanna Kotrba ◽  
Evelyn Gaffal ◽  
Konstantinos Katsoulis-Dimitriou ◽  
Anne Dudeck

Mast cells (MCs) are best-known as key effector cells of immediate-type allergic reactions that may even culminate in life-threatening anaphylactic shock syndromes. However, strategically positioned at the host–environment interfaces and equipped with a plethora of receptors, MCs also play an important role in the first-line defense against pathogens. Their main characteristic, the huge amount of preformed proinflammatory mediators embedded in secretory granules, allows for a rapid response and initiation of further immune effector cell recruitment. The same mechanism, however, may account for detrimental overshooting responses. MCs are not only detrimental in MC-driven diseases but also responsible for disease exacerbation in other inflammatory disorders. Focusing on the skin as the largest immune organ, we herein review both beneficial and detrimental functions of skin MCs, from skin barrier integrity via host defense mechanisms to MC-driven inflammatory skin disorders. Moreover, we emphasize the importance of IgE-independent pathways of MC activation and their role in sustained chronic skin inflammation and disease exacerbation.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Jee-Yeong Jeong ◽  
Jiwook Kim ◽  
Bokyoum Kim ◽  
Joowon Kim ◽  
Yusom Shin ◽  
...  

Mucus secretion is often uncontrolled in many airway inflammatory diseases of humans. Identifying the regulatory pathway(s) of mucus gene expression, mucus overproduction, and hypersecretion is important to alleviate airway inflammation in these diseases. However, the regulatory signaling pathway controlling mucus overproduction has not been fully identified yet. In this study, we report that the ATP/P2Y2complex secretes many cytokines and chemokines to regulate airway inflammation, among which IL-1 receptor antagonist (IL-1ra) downregulatesMUC5ACgene expression via the inhibition of Gαq-induced Ca2+signaling. IL-1ra inhibited IL-1αprotein expression and secretion, and vice versa. Interestingly, ATP/P2Y2-induced IL-1ra and IL-1αsecretion were both mediated by PLCβ3. A dominant-negative mutation in the PDZ-binding domain of PLCβ3 inhibited ATP/P2Y2-induced IL-1ra and IL-1αsecretion. IL-1αin the presence of the ATP/P2Y2complex activated the ERK1/2 pathway in a greater degree and for a longer duration than the ATP/P2Y2complex itself, which was dramatically inhibited by IL-1ra. These findings suggest that secreted IL-1ra exhibits a regulatory effect on ATP/P2Y2-inducedMUC5ACgene expression, through inhibition of IL-1αsecretion, to maintain the mucus homeostasis in the airway. Therefore, IL-1ra could be an excellent modality for regulating inflamed airway microenvironments in respiratory diseases.


2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Daniela Braconi ◽  
Giulia Bernardini ◽  
Annalisa Santucci

Atopic dermatitis and psoriasis are two chronic skin inflammatory diseases that have so far received a greater attention within the scientific community through different post-genomic approaches; on the contrary, acne, which is undoubtedly one of the most common skin disorders involving inflammatory processes, seems to be still quite neglected under the post-genomic point of view. In this paper, we will review how post-genomic technologies have provided new fundamental tools for the analysis of these three conditions and we will cast light on their potential in addressing future research challenges.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Nicholas A Spidale ◽  
Nidhi Malhotra ◽  
Michela Frascoli ◽  
Katelyn Sylvia ◽  
Bing Miu ◽  
...  

Atopic Dermatitis (AD) is a T cell-mediated chronic skin disease and is associated with altered skin barrier integrity. Infants with mutations in genes involved in tissue barrier fitness are predisposed towards inflammatory diseases, but most do not develop or sustain the diseases, suggesting that there exist regulatory immune mechanisms to prevent aberrant inflammation. The absence of one single murine dermal cell type, the innate neonatal-derived IL-17 producing γδ T (Tγδ17) cells, from birth resulted in spontaneous, highly penetrant AD with many of the major hallmarks of human AD. In Tγδ17 cell-deficient mice, basal keratinocyte transcriptome was altered months in advance of AD induction. Tγδ17 cells respond to skin commensal bacteria and the fulminant disease in their absence was driven by skin commensal bacteria dysbiosis. AD in this model was characterized by highly expanded dermal αβ T clonotypes that produce the type three cytokines, IL-17 and IL-22. These results demonstrate that neonatal Tγδ17 cells are innate skin regulatory T cells that are critical for skin homeostasis, and that IL-17 has dual homeostatic and inflammatory function in the skin.


2019 ◽  
Author(s):  
Nicholas Spidale ◽  
Nidhi Malhotra ◽  
Katelyn Sylvia ◽  
Michela Frascoli ◽  
Bing Miu ◽  
...  

ABSTRACTAtopic Dermatitis (AD) is a T cell-mediated chronic skin disease and is associated with altered skin barrier integrity. Infants with mutations in genes involved in tissue barrier fitness are predisposed towards inflammatory diseases, but most do not develop or sustain the diseases, suggesting that there exist regulatory immune mechanisms to repair tissues and/or prevent aberrant inflammation. The absence of one single murine dermal cell type, the innate neonatal-derived IL-17 producing γδ T (Tγδ17) cells, from birth resulted in spontaneous, highly penetrant AD with all the major hallmarks of human AD. In Tγδ17 cell-deficient mice, basal keratinocyte transcriptome was altered months in advance of AD induction. Fulminant disease is driven by skin commensal bacteria dysbiosis and highly expanded dermal αβ T clonotypes that produce the type three cytokines, IL-17 and IL-22. These results demonstrate that neonatal Tγδ17 cells are innate skin regulatory T cells. The bifurcation of type 3 cytokine producing skin T cells into the homeostatic, early innate and pathogen-sensing, late adaptive T cell compartments underpin healthy skin and accounts for the dual function of type 3 cytokines in skin maintenance and inflammation.


Author(s):  
Martin Voss ◽  
Johanna Kotrba ◽  
Evelyn Gaffal ◽  
Konstantinos Katsoulis-Dimitriou ◽  
Anne Dudeck

Mast cells (MCs) are best known as key effector cells of immediate type allergic reactions that may even culminate in life-threatening anaphylactic shock syndromes. However, strategically positioned at host-environment interfaces and equipped with a plethora of receptors, MCs also play an important role in the first line defense against pathogens. Their main characteristic, the huge amount of preformed pro-inflammatory mediators embedded in secretory granules, allow for a rapid response and initiation of further immune effector cell recruitment. The same mechanism, however, may account for detrimental overshooting responses. MCs are not only detrimental in MC-driven diseases, but also responsible for disease exacerbation in other inflammatory disorders. Focusing on the skin as the largest immune organ, we herein review both beneficial and detrimental functions of skin MCs all the way from skin barrier integrity via host defense mechanisms to MC-driven inflammatory skin disorders. Moreover, we emphasize the importance of IgE-independent pathways of MC activation and their role in sustained chronic skin inflammation and disease exacerbation.


Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1290 ◽  
Author(s):  
Denis Nchang Che ◽  
Byoung Ok Cho ◽  
Jae Young Shin ◽  
Hyun Ju Kang ◽  
Ji-Su Kim ◽  
...  

IL-31 is a recently discovered cytokine that is produced not only in T-cells but also in mast cells. It is strongly implicated to play a key role in inflammatory diseases and in the pathogenesis of itch in atopic dermatitis. Apigenin, a flavonoid of plant origin has numerous biological applications. In this study, we showed that apigenin modulates IL-31 mRNA, protein expression, and release in stimulated human mast (HMC-1) by inhibiting the phosphorylation activation of MAPK and NF-κB. To determine whether apigenin has similar effects in vivo, using Compound 48/80, we developed an atopic dermatitis itch model in mice and found an increase in IL-31 expression in the skin. We also revealed that apigenin prevents the infiltration and degranulation of mast cells and suppressed mRNA and protein expression of IL-31 in the skin of mice. These results provide a new suggestion of the potential applicability of apigenin for treatment of various inflammatory diseases and itch mediated by IL-31.


2000 ◽  
Vol 111 (4) ◽  
pp. 1118-1121 ◽  
Author(s):  
A. Bellahcene ◽  
I. Van Riet ◽  
C. de Greef ◽  
N. Antoine ◽  
M. F. Young ◽  
...  

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