scholarly journals Clinical Application of Development of Nonantibiotic Macrolides That Correct Inflammation-Driven Immune Dysfunction in Inflammatory Skin Diseases

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Carmen Rodriguez-Cerdeira ◽  
Elena Sanchez-Blanco ◽  
Alberto Molares-Vila

Background. Inflammation-driven immune dysfunction supports the development of several chronic human disorders including skin diseases. Nonantibiotic macrolides have anti-inflammatory and/or immunomodulatory activity that suggests the exploitation of these in the treatment of skin diseases characterized by inflammatory disorders.Materials and Methods. We performed an extensive review of the nonantibiotic macrolide literature published between 2005 and 2012, including cross-references of any retrieved articles. We also included some data from our own experience.Results. Calcineurin antagonists such as tacrolimus and ascomycins (e.g., pimecrolimus) act by inhibiting the activation of the nuclear factor for activated T cells (NFAT). There are new applications for these macrolides that have been available for several years and have been applied to skin and hair disorders such as atopic dermatitis, oral lichen planus, vitiligo, chronic autoimmune urticaria, rosacea, alopecia areata, pyoderma gangrenosum, Behcet’s disease, neutrophilic dermatosis, and lupus erythematosus. We also reviewed new macrolides, like rapamycin, everolimus, and temsirolimus. In addition to the literature review, we report a novel class of nonantibiotic 14-member macrocycle with anti-inflammatory and immunomodulatory effects.Conclusions. This paper summarizes the most important clinical studies and case reports dealing with the potential benefits of nonantibiotic macrolides which have opened new avenues in the development of anti-inflammatory strategies in the treatment of cutaneous disorders.

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0250216
Author(s):  
Heera Lee ◽  
You Chan Kim ◽  
Jee Woong Choi

Alopecia areata (AA) is an autoimmune skin disease caused by chronic inflammation of hair follicles. Chronic inflammatory skin diseases such as psoriasis and lupus erythematosus can increase the risk of cardiovascular diseases. However, the relationship between AA and heart diseases (HDs) remains unclear. Therefore, we conducted this retrospective cohort study to evaluate the risk of subsequent HDs in patients with AA. We reviewed 3770 cases of AA and from 18,850 age, sex, and income level-matched controls from the National Health Insurance Service-National Sample Cohort. In the subgroup analysis, patients who suffered from alopecia totalis, alopecia universalis, and ophiasis were designated as patients with severe AA and patients having the disease for over a year were designated as patients with long-standing AA. As a result, we found that AA was not associated with a higher risk of heart failure, angina pectoris, or myocardial infarction. There was no significant increase in the risk of overall HD associated with AA (adjusted hazard ratio: 1.17; 95% confidence interval: 0.93–1.48; p = 0.177). Neither the severity nor the duration of AA was related to an increased risk of HDs. During the study period, AA patients did not show a significantly higher cumulative incidence of HDs than controls (log-rank p = 0.157). In conclusion, AA does not increase the risk of HD.


2021 ◽  
Author(s):  
Silvia C Rodrigues ◽  
Renato M S Cardoso ◽  
Patricia C Freire ◽  
Claudia F Gomes ◽  
Filipe V Duarte ◽  
...  

Umbilical cord blood (UCB) has long been seen as a rich source of naive cells with strong regenerative potential, likely mediated by small extracellular vesicles (sEV). More recently, small extracellular vesicles (sEV), such as exosomes, have been shown to play essential roles in cell-to-cell communication, via the transport of numerous molecules, including small RNAs. Often explored for their potential as biomarkers, sEV are now known to have regenerative and immunomodulating characteristics, particularly if isolated from stem cell-rich tissues. In this study, we aim to characterize the immunomodulating properties of umbilical cord blood mononuclear cell sEV (herein referred as Exo-101), and explore their therapeutic potential for inflammatory skin diseases. Exo-101 was shown to shift macrophages toward an anti-inflammatory phenotype, which in turn exert paracrine effects on fibroblasts, despite previous inflammatory stimuli. Additionally, the incubation of PBMC with Exo-101 resulted in an reduction of total CD4+ and CD8+ T-cell proliferation and cytokine release, while specifically supporting the development of regulatory T-cells (Treg), by influencing FOXP3 expression. In a 3D model of psoriatic skin, Exo-101 reduced the expression of inflammatory and psoriatic markers IL-6, IL-8, CXCL10, COX-2, S100A7 and DEFB4. In vivo, Exo-101 significantly prevented or reversed acanthosis in imiquimod-induced psoriasis, and tendentially increased the number of Treg in skin, without having an overall impact on disease burden. This work provides evidence for the anti-inflammatory and tolerogenic effect of Exo-101, which may be harnessed for the treatment of Th17-driven inflammatory skin diseases, such as psoriasis.


Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2342 ◽  
Author(s):  
You Kim ◽  
Dong Kim ◽  
Chae Park ◽  
Tae Park ◽  
Byoung Park

Nymphoides indica, an aquatic plant, is used as folk medicine in some countries. Our previous study demonstrated that the methanol extract of N. indica inhibited the activity of tyrosinases, tyrosine related protein (TRP)1 and TRP2, and microphthalmia-associated transcription factor, as well as the activity of protein kinase A, by effectively inhibiting cyclic adenosine monophosphate. Although the biological activities of N. indica extract have been reported, there are no reports on the skin bioactivity of the main compound(s) on human keratinocytes. This study investigated the anti-inflammatory and moisturizing effects of quercetin 3,7-dimethyl ether 4′-glucoside (QDG) isolated from N. indica. In brief, ultraviolet B irradiated keratinocytes were pretreated with different concentrations of QDG, and the effects of QDG on various inflammatory markers were determined. QDG significantly inhibited inflammation-related cytokines and chemokines and enhanced the activation of skin barrier factors. Additionally, QDG also attenuated phosphorylation inhibition of the upstream cytokines and nuclear factor-κB expression. These results suggest that QDG isolated from N. indica may serve as a potential source of bioactive substances for chronic inflammatory skin diseases.


2018 ◽  
Vol 16 (1) ◽  
pp. 66-69
Author(s):  
Smriti Shrestha ◽  
Alisha Aryal

Pyoderma gangrenosum is an uncommon neutrophilic dermatosis, seen on legs, and infrequently on hands and other anatomical sites. It is associated with systemic diseases in 50-70% of the cases. Antinuclear antibody (ANA) seropositivity has been reported in pyoderma gangrenosum associated with connective tissue disorders. However, there are very few case reports of pyoderma gangrenosum in patients of systemic lupus erythematosus, while we did not find any reports of ANA seropositivity in isolated pyoderma gangrenosum. Hence, we report this unique case of pyoderma gangrenosum with classical clinicohistopathology, positive ANA but no systemic association. As anticipated, our patient responded promptly to steroids.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Chanyong Yun ◽  
Youngchul Jung ◽  
Wonjoo Chun ◽  
Beodeul Yang ◽  
Junghyun Ryu ◽  
...  

The leaves ofArtemisia argyiLev. et Vant. andA. princepsPamp. are well known medicinal herbs used to treat patients in China, Japan, and Korea with skin problems such as eczema and itching, as well as abdominal pain and dysmenorrhoea. We investigated the anti-inflammatory effects ofArtemisialeaf extract (ALE) using CD mice and Raw 264.7 cells. The effects of ALE on histopathological changes and cytokine production in ear tissues were assessed in mice with CD induced by 1-fluoro-2,4-dinitrobenzene (DNFB). Moreover, the anti-inflammatory effects on production levels of prostaglandin E2(PGE2) and nitric oxide (NO) and expression levels of cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) were investigated in Raw 264.7 cells. Topical application of ALE effectively prevented ear swelling induced by repeated DNFB application. ALE prevented epidermal hyperplasia and infiltration of immune cells and lowered the production of interferon- (IFN-) gamma (γ), tumour necrosis factor- (TNF-) alpha (α), and interleukin- (IL-) 6 in inflamed tissues. In addition, ALE inhibited expression of COX-2 and iNOS and production of NO and PGE2in Raw 264.7 cells. These results indicate thatArtemisialeaf can be used as a therapeutic agent for inflammatory skin diseases and that its anti-inflammatory effects are closely related to the inhibition of inflammatory mediator release from macrophages and inflammatory cytokine production in inflamed tissues.


2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Lulli Daniela ◽  
Potapovich Alla ◽  
Riccardo Maurelli ◽  
Dellambra Elena ◽  
Pressi Giovanna ◽  
...  

Edelweiss (Leontopodium alpinumCass.) is traditionally employed in folk medicine as an anti-inflammatory remedy. In nature, the plant is sparsely available and protected; therefore production of callus cultures was established. A concentrated ethanolic extract of culture homogenate, with leontopodic acid representing55±2% of the total phenolic fraction (ECC55), was characterized for anti-inflammatory properties in primary human keratinocytes (PHKs) and endotheliocytes (HUVECs). Inflammatory responses were induced by UVA+UVB, lipopolysaccharide (LPS), oxidized low-density lipoprotein (oxLDL), and a mixture of proinflammatory cytokines. Trichostatin A, a sirtuin inhibitor, was used to induce keratinocyte inflammatory senescence. ECC55 (10–50 μg/mL) protected PHK from solar UV-driven damage, by enhancing early intracellular levels of nitric oxide, although not affecting UV-induced expression of inflammatory genes. Comparison of the dose-dependent inhibition of chemokine (IL-8, IP-10, MCP-1) and growth factor (GM-CSF) release from PHK activated by TNFα+ IFNγshowed that leontopodic acid was mainly responsible for the inhibitory effects of ECC55. Sirtuin-inhibited cell cycle, proliferation, and apoptosis markers were restored by ECC55. The extract inhibited LPS-induced IL-6 and VCAM1 genes in HUVEC, as well as oxLDL-induced selective VCAM1 overexpression.Conclusion.Edelweiss cell cultures could be a valuable source of anti-inflammatory substances potentially applicable for chronic inflammatory skin diseases and bacterial and atherogenic inflammation.


Author(s):  
Stefan Tukaj

Numerous epidemiological studies have suggested a link between vitamin D deficiency and the development of various autoimmune diseases, including diabetes mellitus type 1, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis or systemic lupus erythematosus. More recently, such a link has been also proposed for autoimmune bullous diseases (AIBD). This is a relatively rare and potentially life-threatening, organ-specific group of inflammatory skin diseases characterized by the presence of tissue-bound and circulating autoantibodies against various molecules present in desmosomes (in pemphigus diseases) or hemidesmosomes (in pemphigoid diseases). In addition to the well-known role of vitamin D in calcium and phosphate homeostasis, the hormonally active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (calcitriol), exerts potent effects on cellular differentiation and regulation of immune responses via binding to the vitamin D receptor present in most cells of the immune system. Since cells of both, the innate and adaptive immune systems, are known to be relevant in AIBD, the role of vitamin D analogues in the treatment of patients with these disorders deserves much attention. This mini-review summarizes recent epidemiological and experimental studies on vitamin D involvement in the autoimmune bullous diseases.


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