scholarly journals An Important Role of Blood and Lymphatic Vessels in Inflammation and Allergy

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Silvana Zgraggen ◽  
Alexandra M. Ochsenbein ◽  
Michael Detmar
Keyword(s):  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Experimental Studies ◽  
Lymphatic Vessels ◽  
Allergic Inflammation ◽  
Skin Inflammation ◽  
Chronic Inflammatory Diseases ◽  
Chronic Skin ◽  
Targeted Inhibition ◽  
Endothelial Growth Factor

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.

scholarly journals TWEAK/Fn14 Activation Participates in Skin Inflammation

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Qilu Liu ◽  
Shengxiang Xiao ◽  
Yumin Xia
Keyword(s):  
Cell Fate ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Biological Activities ◽  
Inflammatory Cells ◽  
Skin Inflammation ◽  
Tnf Receptor ◽  
Inflammatory Infiltration ◽  
Papillomavirus Infection ◽  
Chemotactic Protein

Tumor necrosis factor- (TNF-) like weak inducer of apoptosis (TWEAK) participates in multiple biological activities via binding to its sole receptor—fibroblast growth factor-inducible 14 (Fn14). The TWEAK/Fn14 signaling pathway is activated in skin inflammation and modulates the inflammatory responses of keratinocytes by activating nuclear factor-κB signals and enhancing the production of several cytokines, including interleukins, monocyte chemotactic protein-1, RANTES (regulated on activation, normal T cell expressed and secreted), and interferon gamma-induced protein 10. Mild or transient TWEAK/Fn14 activation contributes to tissular repair and regeneration while excessive or persistent TWEAK/Fn14 signals may lead to severe inflammatory infiltration and tissue damage. TWEAK also regulates cell fate of keratinocytes, involving the function of Fn14-TNF receptor-associated factor-TNF receptor axis. By recruiting inflammatory cells, promoting cytokine production, and regulating cell fate, TWEAK/Fn14 activation plays a pivotal role in the pathogenesis of various skin disorders, such as psoriasis, atopic dermatitis, cutaneous vasculitis, human papillomavirus infection and related skin tumors, and cutaneous autoimmune diseases. Therefore, the TWEAK/Fn14 pathway may be a potential target for the development of novel therapeutics for skin inflammatory diseases.

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
Keyword(s):  
Protein Expression ◽  
Inflammatory Diseases ◽  
Skin Barrier ◽  
Skin Inflammation ◽  
New Drugs ◽  
Inflammatory Biomarker ◽  
Cytokines And Chemokines ◽  
Inflammatory Stimuli ◽  
Mrna And Protein Expression ◽  
Chronic Skin

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.

scholarly journals NF-κB/AP-1-Targeted Inhibition of Macrophage-Mediated Inflammatory Responses by Depigmenting Compound AP736 Derived from Natural 1,3-Diphenylpropane Skeleton

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Van Thai Ha ◽  
Heung Soo Beak ◽  
Eunji Kim ◽  
Kwang-Soo Baek ◽  
Muhammad Jahangir Hossen ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Morphological Changes ◽  
Skin Inflammation ◽  
No Synthase ◽  
Raw264.7 Cells ◽  
Inflammatory Gene Expression ◽  
Anti Inflammatory ◽  
Targeted Inhibition ◽  
Tyrosinase Expression ◽  
Phagocytic Uptake

AP736 was identified as an antimelanogenic drug that can be used for the prevention of melasma, freckles, and dark spots in skin by acting as a suppressor of melanin synthesis and tyrosinase expression. Since macrophage-mediated inflammatory responses are critical for skin health, here we investigated the potential anti-inflammatory activity of AP736. The effects of AP736 on various inflammatory events such as nitric oxide (NO)/prostaglandin (PG) E2production, inflammatory gene expression, phagocytic uptake, and morphological changes were examined in RAW264.7 cells. AP736 was found to strongly inhibit the production of both NO and PGE2in lipopolysaccharide- (LPS-) treated RAW264.7 cells. In addition, AP736 strongly inhibited both LPS-induced morphological changes and FITC-dextran-induced phagocytic uptake. Furthermore, AP736 also downregulated the expression of multiple inflammatory genes, such as inducible NO synthase (iNOS), cyclooxygenase- (COX-) 2, and interleukin- (IL-) 1βin LPS-treated RAW264.7 cells. Transcription factor analysis, including upstream signalling events, revealed that both NF-κB and AP-1 were targeted by AP736 via inhibition of the IKK/IκBαand IRAK1/TAK1 pathways. Therefore, our results strongly suggest that AP736 is a potential anti-inflammatory drug due to its suppression of NF-κB-IKK/IκBαand AP-1-IRAK1/TAK1 signalling, which may make AP736 useful for the treatment of macrophage-mediated skin inflammation.

scholarly journals IL-1 Family Antagonists in Mouse and Human Skin Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Praxedis Martin ◽  
Jérémie D. Goldstein ◽  
Loïc Mermoud ◽  
Alejandro Diaz-Barreiro ◽  
Gaby Palmer
Keyword(s):  
Skin Diseases ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Skin Inflammation ◽  
Cell Type ◽  
Inflammatory Skin Diseases ◽  
Innate And Adaptive Immunity ◽  
Skin Biology

Interleukin (IL)-1 family cytokines initiate inflammatory responses, and shape innate and adaptive immunity. They play important roles in host defense, but excessive immune activation can also lead to the development of chronic inflammatory diseases. Dysregulated IL-1 family signaling is observed in a variety of skin disorders. In particular, IL-1 family cytokines have been linked to the pathogenesis of psoriasis and atopic dermatitis. The biological activity of pro-inflammatory IL-1 family agonists is controlled by the natural receptor antagonists IL-1Ra and IL-36Ra, as well as by the regulatory cytokines IL-37 and IL-38. These four anti-inflammatory IL-1 family members are constitutively and highly expressed at steady state in the epidermis, where keratinocytes are a major producing cell type. In this review, we provide an overview of the current knowledge concerning their regulatory roles in skin biology and inflammation and their therapeutic potential in human inflammatory skin diseases. We further highlight some common misunderstandings and less well-known observations, which persist in the field despite recent extensive interest for these cytokines.

scholarly journals Immune-Mediated Retinal Vasculitis in Posterior Uveitis and Experimental Models: The Leukotriene (LT)B4-VEGF Axis

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 396
Author(s):  
Malihe Eskandarpour ◽  
Miles A. Nunn ◽  
Wynne Weston-Davies ◽  
Virginia L. Calder
Keyword(s):  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Retinal Vasculitis ◽  
Vascular Diseases ◽  
Leukotriene B4 ◽  
Experimental Models ◽  
Posterior Uveitis ◽  
Angiogenic Factor ◽  
Immune Mediated ◽  
Endothelial Growth Factor

Retinal vascular diseases have distinct, complex and multifactorial pathogeneses yet share several key pathophysiological aspects including inflammation, vascular permeability and neovascularisation. In non-infectious posterior uveitis (NIU), retinal vasculitis involves vessel leakage leading to retinal enlargement, exudation, and macular oedema. Neovascularisation is not a common feature in NIU, however, detection of the major angiogenic factor—vascular endothelial growth factor A (VEGF-A)—in intraocular fluids in animal models of uveitis may be an indication for a role for this cytokine in a highly inflammatory condition. Suppression of VEGF-A by directly targeting the leukotriene B4 (LTB4) receptor (BLT1) pathway indicates a connection between leukotrienes (LTs), which have prominent roles in initiating and propagating inflammatory responses, and VEGF-A in retinal inflammatory diseases. Further research is needed to understand how LTs interact with intraocular cytokines in retinal inflammatory diseases to guide the development of novel therapeutic approaches targeting both inflammatory mediator pathways.

scholarly journals The Anti-Inflammatory Effect of Aptamin C on House Dust Mite Extract-Induced Inflammation in Keratinocytes via Regulation of IL-22 and GDNF Production

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 945
Author(s):  
Dahae Lee ◽  
Yejin Kim ◽  
Hyejung Jo ◽  
Cheolhyeon Go ◽  
Yoojin Jeong ◽  
...  
Keyword(s):  
Vitamin C ◽  
Cell Line ◽  
House Dust ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Skin Inflammation ◽  
Skin Lesions ◽  
House Dust Mites ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Atopic dermatitis (AD), a chronic inflammatory skin disease, is characterized by eczemous lesions on the skin that manifest as severe itching and last a long time. AD is thought to be a response to local allergens, including house dust mites (HDMs). Aptamin C is a modified form of vitamin C comprised of aptamers (DNA fragments) that bind specifically to vitamin C and inhibit its oxidation, thereby increasing its stability and antioxidant effects. It is already known that vitamin C shows an anti-inflammatory effect on skin inflammation. Oxidative stress is one of the major causes of inflammatory diseases, including HDM-induced skin inflammation, suggesting that the antioxidant activity of Aptamin C could regulate inflammatory responses to HDMs in the skin keratinocyte cell line HaCaT and primary skin keratinocytes. Aptamin C not only inhibited HDM-induced proliferation of both type of cells, but suppressed HDM-induced increases in interleukin (IL)-1α and IL-6 production by these cells. In addition, Aptamin C suppressed the production of IL-17 and IL-22 by T cells, which are closely associated with AD pathogenesis, as well as HDM-induced IL-22Rα expression. Aptamin C also reduced the production of thymus and activation-regulated chemokine (TARC) by suppressing the interaction between IL-22 and IL-22Rα, as well as reducing T cell migration. Although HDM treatment markedly increased the expression of glial cell line-derived neurotrophic factor (GDNF), which is associated with itching in AD skin lesions, this increase was reduced by Aptamin C treatment. Taken together, these results suggest that Aptamin C can effectively regulate inflammatory lesions, such as AD, by regulating the production of inflammatory cytokines and GDNF induced by HDM.

scholarly journals Identifying hidden drivers of heterogeneous inflammatory diseases

2020 ◽  
Author(s):  
Natalie Garzorz-Stark ◽  
Richa Batra ◽  
Felix Lauffer ◽  
Manja Jargosch ◽  
Caroline Pilz ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Skin Inflammation ◽  
Key Factors ◽  
Chronic Inflammatory Diseases ◽  
Biologically Relevant ◽  
Complex Interactions ◽  
Enhancer Binding Protein ◽  
Methodological Advance ◽  
Clinical Phenotyping

AbstractChronic inflammatory diseases of the cardiovascular system, brain, gut, joints, skin and lung are characterized by complex interactions between genetic predisposition and tissuespecific immune responses. This heterogeneity complicates diagnoses and the ability to exploit omics approaches to improve disease management, develop more effective therapeutics, and apply precision medicine. Using skin inflammation as a model, we developed a bio-computational approach that assigns deep clinical phenotyping information to transcriptome data of lesional and non-lesional skin (564 samples) to identify biologically-relevant gene signatures. This identified previously unknown key factors, including CCAAT Enhancer-Binding Protein Beta (CEBPB) in neutrophil invasion, and Pituitary Tumor-Transforming 2 (PTTG2) in the pathogenic epithelial response to inflammation. These were validated using genetically-modified human skin equivalents, migration assays, and in situ imaging. Thus, by combining deep clinical phenotyping and omics data with sophisticated bio-computational algorithms we present a methodological advance to identify hidden drivers of clinically-relevant biological processes within omics datasets.One Sentence SummaryDeciphering the pathogenesis of chronic inflammatory diseases by assigning transcriptome profiles to deep clinical phenotyping.

scholarly journals Macrophage Polarization in Chronic Inflammatory Diseases: Killers or Builders?

2018 ◽  
Vol 2018 ◽  
pp. 1-25 ◽  
Author(s):  
Luca Parisi ◽  
Elisabetta Gini ◽  
Denisa Baci ◽  
Marco Tremolati ◽  
Matteo Fanuli ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Macrophage Polarization ◽  
Cancer Type ◽  
Effector Cells ◽  
Chronic Inflammatory Diseases ◽  
Pathological Conditions ◽  
Cellular Components ◽  
Cell Cell

Macrophages are key cellular components of the innate immunity, acting as the main player in the first-line defence against the pathogens and modulating homeostatic and inflammatory responses. Plasticity is a major feature of macrophages resulting in extreme heterogeneity both in normal and in pathological conditions. Macrophages are not homogenous, and they are generally categorized into two broad but distinct subsets as either classically activated (M1) or alternatively activated (M2). However, macrophages represent a continuum of highly plastic effector cells, resembling a spectrum of diverse phenotype states. Induction of specific macrophage functions is closely related to the surrounding environment that acts as a relevant orchestrator of macrophage functions. This phenomenon, termed polarization, results from cell/cell, cell/molecule interaction, governing macrophage functionality within the hosting tissues. Here, we summarized relevant cellular and molecular mechanisms driving macrophage polarization in “distant” pathological conditions, such as cancer, type 2 diabetes, atherosclerosis, and periodontitis that share macrophage-driven inflammation as a key feature, playing their dual role as killers (M1-like) and/or builders (M2-like). We also dissect the physio/pathological consequences related to macrophage polarization within selected chronic inflammatory diseases, placing polarized macrophages as a relevant hallmark, putative biomarkers, and possible target for prevention/therapy.

scholarly journals Immunosuppression of the Trimellitic Anhydride-Induced Th2 Response by Novel Nonanatural Products Mixture in Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Min-Jung Bae ◽  
Hee Soon Shin ◽  
Dong-Hwa Shon
Keyword(s):  
Oral Administration ◽  
Inflammatory Diseases ◽  
Allergic Inflammation ◽  
Skin Inflammation ◽  
Specific Ige ◽  
Contact Hypersensitivity ◽  
Inhibitory Effects ◽  
Trimellitic Anhydride ◽  
Th2 Response ◽  
Allergic Skin

Many natural dietary products prevent or cure allergic inflammation; however, the ability of mixtures of these natural medicinals to suppress allergic skin inflammation is unknown. We examined the inhibitory effects of nonanatural products mixture (NPM-9), which provides immunoregulatory activation, on Th2-mediated skin allergic inflammation. Oral administration of NPM-9 in mice reduced ear thickness and specific IgE production in trimellitic anhydride- (TMA-)induced contact hypersensitivity (CHS). NPM-9 also suppressed IL-4 and IL-1βproduction in splenocytes but prevented only TMA-induced IL-1βproduction in inflamed ears. To characterize the mechanism of this effect, we examined NPM-9 immunosuppression on an OVA-induced Th2 allergic state. Oral administration of NPM-9 inhibited Th2-mediated serum IgE overproduction. NPM-9 also downregulated the polarized Th2 response, whereas it upregulated Th1 response in splenocytes. These data suggest that NPM-9 may be a useful therapeutic agent for allergic inflammatory diseases through its suppression of the Th2-mediated allergic response.

scholarly journals Post-Genomics and Skin Inflammation

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Daniela Braconi ◽  
Giulia Bernardini ◽  
Annalisa Santucci
Keyword(s):  
Scientific Community ◽  
Inflammatory Diseases ◽  
Skin Inflammation ◽  
Point Of View ◽  
Future Research ◽  
Genomic Technologies ◽  
Research Challenges ◽  
Common Skin ◽  
Inflammatory Processes ◽  
Chronic Skin

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.

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