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 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.

Osteopontin and Mucosal Protection

2006 ◽  
Vol 85 (5) ◽  
pp. 404-415 ◽  
Author(s):  
J. Sodek ◽  
A. Paes Batista Da Silva ◽  
R. Zohar
Keyword(s):  
Immune Cells ◽  
Barrier Function ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Biological Activities ◽  
Proteolytic Processing ◽  
Mucosal Inflammation ◽  
Tissue Destruction ◽  
Mucosal Tissues

Protection of mucosal tissues of the oral cavity, intestines, respiratory tract, and urogenital tract from the constant challenge of pathogens is achieved by the combined barrier function of the lining epithelia and specialized immune cells. Recent studies have indicated that osteopontin (OPN) has a pivotal role in the development of immune responses and in the tissue destruction and the subsequent repair processes associated with inflammatory diseases. While expression of OPN is increased in immune cells—including neutrophils, macrophages, T- and B-lymphocytes—and in epithelial, endothelial, and fibroblastic cells of inflamed tissues, deciphering the specific functions of OPN has been difficult. In part, this is due to the broad range of biological activities of OPN that are mediated by multiple receptors which recognize several signaling motifs whose activities are influenced by post-translational modifications and proteolytic processing of OPN. Understanding the role of OPN in mucosal inflammation is further complicated by its contributions to the barrier function of the lining epithelia and the complexity of the specialized mucosal immune system. In an attempt to provide some insights into the involvement of OPN in mucosal diseases, this review summarizes current knowledge of the biological activities of OPN involved in the development of inflammatory responses and in wound healing, and indicates how these activities may affect the protection of mucosal tissues.

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 Dooming Phagocyte Responses: Inflammatory Effects of Endogenous Oxidized Phospholipids

2021 ◽  
Vol 12 ◽  
Author(s):  
Marco Di Gioia ◽  
Ivan Zanoni
Keyword(s):  
Immune Cells ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Biological Activities ◽  
Oxidized Lipids ◽  
Oxidized Phospholipids ◽  
Clinical Tools ◽  
Stress Mediators ◽  
The Impact

Endogenous oxidized phospholipids are produced during tissue stress and are responsible for sustaining inflammatory responses in immune as well as non-immune cells. Their local and systemic production and accumulation is associated with the etiology and progression of several inflammatory diseases, but the molecular mechanisms that underlie the biological activities of these oxidized phospholipids remain elusive. Increasing evidence highlights the ability of these stress mediators to modulate cellular metabolism and pro-inflammatory signaling in phagocytes, such as macrophages and dendritic cells, and to alter the activation and polarization of these cells. Because these immune cells serve a key role in maintaining tissue homeostasis and organ function, understanding how endogenous oxidized lipids reshape phagocyte biology and function is vital for designing clinical tools and interventions for preventing, slowing down, or resolving chronic inflammatory disorders that are driven by phagocyte dysfunction. Here, we discuss the metabolic and signaling processes elicited by endogenous oxidized lipids and outline new hypotheses and models to elucidate the impact of these lipids on phagocytes and inflammation.

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 Interleukin-15 (IL-15) Induces IL-8 and Monocyte Chemotactic Protein 1 Production in Human Monocytes

Blood ◽  
1997 ◽  
Vol 90 (7) ◽  
pp. 2804-2809 ◽  
Author(s):  
Raffaele Badolato ◽  
Alessandro Negro Ponzi ◽  
Maura Millesimo ◽  
Luigi D. Notarangelo ◽  
Tiziana Musso
Keyword(s):  
Inflammatory Diseases ◽  
Biological Activities ◽  
Fibroblast Cell ◽  
Interferon Γ ◽  
Enzyme Linked Immunosorbent Assay ◽  
Monocyte Chemotactic Protein ◽  
Chemotactic Protein ◽  
Interleukin 15 ◽  
Ifn Γ ◽  
High Concentrations

Interleukin-15 (IL-15) is a recently characterized cytokine that shares many biological activities with IL-2 and interacts with the β and γ components of the IL-2 receptor. Unlike IL-2, which is secreted only by T cells, IL-15 is expressed preferentially by nonlymphoid tissues, epithelial, and fibroblast cell lines and by activated monocytes/macrophages. High concentrations of IL-15 have been shown in inflamed joints of rheumatoid arthritis patients, suggesting a role for IL-15 in inflammatory diseases where there is recruitment of leukocytes. Although monocytes have been shown to bind IL-15, its effects on these cells are not defined. In this report we show that supernatants of monocytes treated with IL-15–contained chemotactic activity for neutrophils and monocytes which was neutralized by anti-IL-8 or by anti-monocyte chemotactic protein 1 (MCP-1) antibodies, respectively. Secretion of IL-8 and MCP-1 proteins is detectable by enzyme-linked immunosorbent assay as early as 6 hours after stimulation with IL-15. Production of the two chemokines is correlated with induction by IL-15 of mRNA expression in monocytes. In addition, IL-8 and MCP-1 induction by IL-15 is differently regulated by interferon-γ (IFN-γ) and IL-4. IFN-γ inhibited IL-15–induced IL-8 secretion, but synergized with IL-15 in MCP-1 induction; whereas IL-4 inhibited both IL-8 and MCP-1 induction by IL-15. These results show that IL-15 can stimulate monocytes to produce chemokines that cause inflammatory cell accumulation. Thus, IL-15 locally produced at sites of inflammation may play a pivotal role in the regulation of the leukocyte infiltrate.

Anti-Inflammatory Activity of Lobaric Acid via Suppressing NF-κB/MAPK Pathways or NLRP3 Inflammasome Activation

Planta Medica ◽  
2018 ◽  
Vol 85 (04) ◽  
pp. 302-311 ◽  
Author(s):  
Hee-Weon Lee ◽  
JinWook Kim ◽  
Joung-Han Yim ◽  
Hong-Kum Lee ◽  
Suhkneung Pyo
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Biological Activities ◽  
Inflammasome Activation ◽  
Mapk Pathways ◽  
Nlrp3 Inflammasome Activation ◽  
Mitogen Activated Protein ◽  
Factor Α ◽  
Necrosis Factor

Lobaric acid (LA) is a constituent of the lichen Stereocaulon alpinum. LA has multiple biological activities, including antibacterial and antioxidant ones. The purpose of this study was to investigate the effect of LA and its mechanism on lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. Macrophages were pretreated with different concentrations of LA (0.2 – 20 µM), followed by LPS stimulation. LA treatment of LPS stimulated macrophages decreased their nitric oxide production and the expression of cyclooxygenase-2 and prostaglandin E2. LA also significantly reduced the production of tumor necrosis factor-α and interleukin (IL)-6 by inhibiting the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB). Additionally, LA inhibited the production of IL-1β and IL-18, as well as caspase-1 maturation, by inhibition of NLRP3 inflammasome activation in LPS/ATP-stimulated cells. These results strongly suggest that LA could inhibit inflammation by downregulating NF-κB/MAPK pathways and NLRP3 inflammasome activation in activated macrophages. These results reveal a new therapeutic approach to modulate inflammatory diseases linked to deregulated inflammasome activities.

scholarly journals Interleukin-15 (IL-15) Induces IL-8 and Monocyte Chemotactic Protein 1 Production in Human Monocytes

Blood ◽  
1997 ◽  
Vol 90 (7) ◽  
pp. 2804-2809 ◽  
Author(s):  
Raffaele Badolato ◽  
Alessandro Negro Ponzi ◽  
Maura Millesimo ◽  
Luigi D. Notarangelo ◽  
Tiziana Musso
Keyword(s):  
Inflammatory Diseases ◽  
Biological Activities ◽  
Fibroblast Cell ◽  
Interferon Γ ◽  
Enzyme Linked Immunosorbent Assay ◽  
Monocyte Chemotactic Protein ◽  
Chemotactic Protein ◽  
Interleukin 15 ◽  
Ifn Γ ◽  
High Concentrations

Abstract Interleukin-15 (IL-15) is a recently characterized cytokine that shares many biological activities with IL-2 and interacts with the β and γ components of the IL-2 receptor. Unlike IL-2, which is secreted only by T cells, IL-15 is expressed preferentially by nonlymphoid tissues, epithelial, and fibroblast cell lines and by activated monocytes/macrophages. High concentrations of IL-15 have been shown in inflamed joints of rheumatoid arthritis patients, suggesting a role for IL-15 in inflammatory diseases where there is recruitment of leukocytes. Although monocytes have been shown to bind IL-15, its effects on these cells are not defined. In this report we show that supernatants of monocytes treated with IL-15–contained chemotactic activity for neutrophils and monocytes which was neutralized by anti-IL-8 or by anti-monocyte chemotactic protein 1 (MCP-1) antibodies, respectively. Secretion of IL-8 and MCP-1 proteins is detectable by enzyme-linked immunosorbent assay as early as 6 hours after stimulation with IL-15. Production of the two chemokines is correlated with induction by IL-15 of mRNA expression in monocytes. In addition, IL-8 and MCP-1 induction by IL-15 is differently regulated by interferon-γ (IFN-γ) and IL-4. IFN-γ inhibited IL-15–induced IL-8 secretion, but synergized with IL-15 in MCP-1 induction; whereas IL-4 inhibited both IL-8 and MCP-1 induction by IL-15. These results show that IL-15 can stimulate monocytes to produce chemokines that cause inflammatory cell accumulation. Thus, IL-15 locally produced at sites of inflammation may play a pivotal role in the regulation of the leukocyte infiltrate.

scholarly journals IκBζ is a key driver in the development of psoriasis

2015 ◽  
Vol 112 (43) ◽  
pp. E5825-E5833 ◽  
Author(s):  
Claus Johansen ◽  
Maike Mose ◽  
Pernille Ommen ◽  
Trine Bertelsen ◽  
Hanne Vinter ◽  
...  
Keyword(s):  
Target Genes ◽  
Inflammatory Diseases ◽  
Inflammatory Cells ◽  
Human Keratinocytes ◽  
Skin Inflammation ◽  
Intradermal Injection ◽  
Immune Mediated ◽  
Associated Proteins ◽  
Future Strategy ◽  
Deficient Mice

Psoriasis is a common immune-mediated, chronic, inflammatory skin disease characterized by hyperproliferation and abnormal differentiation of keratinocytes and infiltration of inflammatory cells. Although TNFα- and IL-17A–targeting drugs have recently proven to be highly effective, the molecular mechanism underlying the pathogenesis of psoriasis remains poorly understood. We found that expression of the atypical IκB member IκB (inhibitor of NF-κB) ζ, a selective coactivator of particular NF-κB target genes, was strongly increased in skin of patients with psoriasis. Moreover, in human keratinocytes IκBζ was identified as a direct transcriptional activator of TNFα/IL-17A–inducible psoriasis-associated proteins. Using genetically modified mice, we found that imiquimod-induced psoriasis-like skin inflammation was completely absent in IκBζ-deficient mice, whereas skin inflammation was still inducible in IL-17A– and TNFα-deficient mice. IκBζ deficiency also conferred resistance against IL-23–induced psoriasis. In addition, local abrogation of IκBζ function by intradermal injection of IκBζ siRNA abolished psoriasis-like skin inflammation. Taken together, we identify IκBζ as a hitherto unknown key regulator of IL-17A–driven effects in psoriasis. Thus, targeting IκBζ could be a future strategy for treatment of psoriasis, and other inflammatory diseases for which IL-17 antagonists are currently tested in clinical trials.

The Immunomodulatory Role of G2013 (α-L-Guluronic Acid) on the Expression of TLR2 and TLR4 in HT29 cell line

2019 ◽  
Vol 16 (1) ◽  
pp. 91-95 ◽  
Author(s):  
Hamid Farhang ◽  
Laleh Sharifi ◽  
Mohammad Mehdi Soltan Dallal ◽  
Mona Moshiri ◽  
Zahra Norouzbabaie ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Rna Extraction ◽  
Cell Plate ◽  
Inhibitory Effect ◽  
Control Group ◽  
Ht29 Cells ◽  
Guluronic Acid ◽  
Tlr4 Mrna

Background: The non-steroidal anti-inflammatory drugs (NSAIDs) play crucial role in the controlling of inflammatory diseases. Due to the vast side effects of NSAIDs, its use is limited. G2013 or &amp;#945;-L-Guluronic Acid is a new NSAID with immunomodulatory features. Objectives: Considering the leading role of TLRs in inflammatory responses, in this study, we aimed to evaluate G2013 cytotoxicity and its effect on the expression of TLR2 and TLR4 molecules. Methods: HEK293-TLR2 and HEK293-TLR4 cells were cultured and seeded on 96-well cell plate, and MTT assay was performed for detecting the viability of the cells after treatment with different concentrations of G2013. HT29 cells were grown and treated with low and high doses of G2013. After total RNA extraction and cDNA synthesis, quantitative real-time PCR were performed to assess the TLR2 and TLR4 mRNA synthesis. Results: We found that concentrations of ≤125 &amp;#181;g/ml of G2013 had no apparent cytotoxicity effect on the HEK293-TLR2 and -TLR4 cells. Our results indicated that after G2013 treatment (5 &amp;#181;g/ml) in HT29 cells, TLR2 and TLR4 mRNA expression decreased significantly compared with the untreated control group (p=0.02 and p=0.001 respectively). Conclusion: The results of this study revealed that G2013 can down regulate the TLR2 and TLR4 gene expression and exerts its inhibitory effect. Our findings are parallel to our previous finding which showed G2013 ability to down regulate the signaling pathway of TLRs. However, further studies are needed to identify the molecular mechanism of G2013.<p&gt;

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