scholarly journals Cardamonin Inhibits Oxazolone-Induced Atopic Dermatitis by the Induction of NRF2 and the Inhibition of Th2 Cytokine Production

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 834
Author(s):  
Ok-Kyung Yoo ◽  
Won Jun Choi ◽  
Young-Sam Keum
Keyword(s):  
Atopic Dermatitis ◽  
Immune Responses ◽  
Immune Cells ◽  
Natural Compound ◽  
Cytokine Production ◽  
Hypersensitivity Reactions ◽  
Connective Tissues ◽  
Oxidative Damages ◽  
Th2 Cytokine

The skin is constantly exposed to various types of chemical stresses that challenge the immune cells, leading to the activation of T cell-mediated hypersensitivity reactions including atopic dermatitis. Previous studies have demonstrated that a variety of natural compounds are effective against development of atopic dermatitis by modulating immune responses. Cardamonin is a natural compound abundantly found in cardamom spices and many other medicinal plant species. In the present study, we attempted to examine whether cardamonin could inhibit oxazolone-induced atopic dermatitis in vivo. Our results show that topical application of cardamonin onto the ear of mice suppressed oxazolone-induced inflammation in the ear and hyperplasia in the spleen. Cardamonin also inhibited oxazolone-induced destruction of connective tissues and subsequent infiltration of mast cells into the skin. In addition, we found that the production of Th2 cytokines is negatively regulated by NRF2, and the induction of NRF2 by cardamonin contributed to suppressing oxazolone-induced Th2 cytokine production and oxidative damages in vivo. Together, our results demonstrate that cardamonin is a promising natural compound, which might be effective for treatment of atopic dermatitis.

scholarly journals The Implications of Pruritogens in the Pathogenesis of Atopic Dermatitis

2021 ◽  
Vol 22 (13) ◽  
pp. 7227
Author(s):  
Lai-San Wong ◽  
Yu-Ta Yen ◽  
Chih-Hung Lee
Keyword(s):  
Atopic Dermatitis ◽  
Environmental Factors ◽  
Immune Responses ◽  
Immune Cells ◽  
Inflammatory Disease ◽  
Targeted Therapies ◽  
Skin Barrier ◽  
Skin Barrier Function ◽  
Inflammatory Molecules

Atopic dermatitis (AD) is a prototypic inflammatory disease that presents with intense itching. The pathophysiology of AD is multifactorial, involving environmental factors, genetic susceptibility, skin barrier function, and immune responses. A recent understanding of pruritus transmission provides more information about the role of pruritogens in the pathogenesis of AD. There is evidence that pruritogens are not only responsible for eliciting pruritus, but also interact with immune cells and act as inflammatory mediators, which exacerbate the severity of AD. In this review, we discuss the interaction between pruritogens and inflammatory molecules and summarize the targeted therapies for AD.

scholarly journals Murine neonatal recent thymic emigrants are phenotypically and functionally distinct from adult recent thymic emigrants

Blood ◽  
2009 ◽  
Vol 113 (22) ◽  
pp. 5635-5643 ◽  
Author(s):  
Shannon J. Opiela ◽  
Tulay Koru-Sengul ◽  
Becky Adkins
Keyword(s):  
Cytokine Production ◽  
Age Groups ◽  
Recent Thymic Emigrants ◽  
Functional Capabilities ◽  
Interleukin 7 ◽  
Th2 Cytokine ◽  
Transgenic Mouse Strain ◽  
First Time ◽  
Kinetics Of

In contrast to adults, the murine neonatal CD4+ compartment contains a high frequency of recent thymic emigrants (RTEs). However, the functional capabilities of these cells in neonates are relatively unknown. Moreover, it has not been determined whether RTEs from neonates and adults are comparable. Here we have directly compared neonatal and adult CD4+ RTEs for the first time, using a transgenic mouse strain that allows for the identification and purification of RTEs. Our data demonstrate that RTEs from murine neonates and adults are phenotypically and functionally distinct. In particular, although the magnitude of RTEs cytokine responses from both age groups is dependent on the conditions of activation, neonatal RTEs always exhibited higher levels of effector Th1/Th2 cytokine production than adult RTEs. In addition, neonatal, but not adult, RTEs showed early proliferation in response to stimulation with interleukin-7 alone. This was associated with faster kinetics of interleukin-7Rα down-regulation and higher levels of pSTAT5 in neonatal RTEs. These quantitative and qualitative differences in the neonatal and adult RTEs populations may at least partially explain the diverse responses that are elicited in vivo in neonates in response to different conditions of antigen exposure.

scholarly journals Human Mesenchymal Stromal Cell-Mediated Immunoregulation: Mechanisms of Action and Clinical Applications

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Akaitz Dorronsoro ◽  
Jon Fernández-Rueda ◽  
Karoline Fechter ◽  
Izaskun Ferrin ◽  
Juan Manuel Salcedo ◽  
...  
Keyword(s):  
Immune Responses ◽  
Stromal Cells ◽  
Clinical Investigation ◽  
Mechanisms Of Action ◽  
Connective Tissues ◽  
Allogeneic Mscs ◽  
Multipotent Cells ◽  
Regenerative Therapies

Mesenchymal stromal cells (MSCs) are multipotent cells found in connective tissues that can differentiate into bone, cartilage, and adipose tissue. Interestingly, they can regulate immune responses in a paracrine way and allogeneic MSCs do not elicit immune response. These properties have encouraged a number of clinical trials in a broad range of regenerative therapies. Although these trials were first focused on their differentiation properties, in the last years, the immunosuppressive features have gained most of the attention. In this review, we will summarize the up-to-date knowledge about the immunosuppressive mechanisms of MSCs in vivo and in vitro and the most promising approaches in clinical investigation.

scholarly journals How to Prevent and Mitigate Hypersensitivity Reactions to Biologicals Induced by Anti-Drug Antibodies?

2021 ◽  
Vol 12 ◽  
Author(s):  
Alessandra Vultaggio ◽  
Margherita Perlato ◽  
Francesca Nencini ◽  
Emanuele Vivarelli ◽  
Enrico Maggi ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cytokine Production ◽  
Inflammatory Diseases ◽  
Immunosuppressive Treatment ◽  
Complex Structures ◽  
Hypersensitivity Reactions ◽  
Immediate Hypersensitivity ◽  
Rheumatologic Diseases ◽  
Ige Mediated ◽  
Underlying Mechanisms

Biologicals are widely used therapeutic agents for rheumatologic diseases, cancers, and other chronic inflammatory diseases. They are characterized by complex structures and content of variable amounts of foreign regions, which may lead to anti-drug antibodies (ADA) development. ADA onset may limit the clinical usage of biologicals because they may decrease their safety. In fact they are mainly associated with immediate hypersensitivity reactions (HSRs). Development of ADAs is reduced by concomitant immunosuppressive treatment, while it is increased by longer intervals between drug administrations; thus, regular infusion regimens should be preferred to reduce HSRs. Once ADAs have formed, some procedures can be implemented to reduce the risk of HSRs. ADAs may belong to different isotype; the detection of IgE ADA is advisable to be assessed when high and early ADAs are detected, in order to reduce the risk of severe HRs. In patients who need to reintroduce the biological culprit, as alternative therapies are not available, drug desensitization (DD) may be applied. Desensitization should be conceptually dedicated to patients with an IgE-mediated HSR; however, it can be performed also in patients who had developed non-IgE-mediated HSRs. Although the underlying mechanisms behind successful DD has not been fully clarified, the DD procedure is associated with the inhibition of mast cell degranulation and cytokine production. Additionally, some data are emerging about the inhibition of drug-specific immune responses during DD.

Anesthesiologists at work: an increase in pro-inflammatory and Th2 cytokine production, and alterations in proliferative immune responses

2006 ◽  
Vol 50 (10) ◽  
pp. 1223-1228 ◽  
Author(s):  
B. Beilin ◽  
K. Greenfeld ◽  
N. Abiri ◽  
I. Z. Yardeni ◽  
H. Bessler ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cytokine Production ◽  
Th2 Cytokine

Modulatory effects of ozone on THP-1 cells in response to SP-A stimulation

2005 ◽  
Vol 288 (2) ◽  
pp. L317-L325 ◽  
Author(s):  
Branislava Janic ◽  
Todd M. Umstead ◽  
David S. Phelps ◽  
Joanna Floros
Keyword(s):  
Immune Cells ◽  
Cytokine Production ◽  
Cell Damage ◽  
Surfactant Protein ◽  
Proinflammatory Cytokine Production ◽  
Tnf Α ◽  
In Vitro Systems ◽  
Alveolar Proteinosis

Ozone (O3), a major component of air pollution and a strong oxidizing agent, can lead to lung injury associated with edema, inflammation, and epithelial cell damage. The effects of O3on pulmonary immune cells have been studied in various in vivo and in vitro systems. We have shown previously that O3exposure of surfactant protein (SP)-A decreases its ability to modulate proinflammatory cytokine production by cells of monocyte/macrophage lineage (THP-1 cells). In this report, we exposed THP-1 cells and/or native SP-A obtained from bronchoalveolar lavage of patients with alveolar proteinosis to O3and studied cytokine production and NF-κB signaling. The results showed 1) exposure of THP-1 cells to O3significantly decreased their ability to express TNF-α in response to SP-A; TNF-α production, under these conditions, was still significantly higher than basal (unstimulated) levels in filtered air-exposed THP-1 cells; 2) exposure of both THP-1 cells and SP-A to O3did not result in any significant differences in TNF-α expression compared with basal levels; 3) O3exposure of SP-A resulted in a decreased ability of SP-A to activate the NF-κB pathway, as assessed by the lack of significant increase and decrease of the nuclear p65 subunit of NF-κB and cytoplasmic IκBα, respectively; and 4) O3exposure of THP-1 cells resulted in a decrease in SP-A-mediated THP-1 cell responsiveness, which did not seem to be mediated via the classic NF-κB pathway. These findings indicate that O3exposure may mediate its effect on macrophage function both directly and indirectly (via SP-A oxidation) and by involving different mechanisms.

IN VIVO DEPLETION OF CD8+ T CELLS RESULTS IN Th2 CYTOKINE PRODUCTION AND ALTERNATE MECHANISMS OF ALLOGRAFT REJECTION

1995 ◽  
Vol 59 (8) ◽  
pp. 1155-1161
Author(s):  
SHERRI Y. CHAN ◽  
LISA A. DEBRUYNE ◽  
RICHARD E. GOODMAN ◽  
ERNST J. EICHWALD ◽  
D. KEITH BISHOP
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Allograft Rejection ◽  
Cytokine Production ◽  
Th2 Cytokine

scholarly journals The ubiquitin ligase HOIL-1L regulates immune responses by interacting with linear ubiquitin chains

2021 ◽  
Author(s):  
Carlos Gomez Diaz ◽  
Gustav Jonsson ◽  
Katrin Schodl ◽  
Luiza Deszcz ◽  
Annika Bestehorn ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cytokine Production ◽  
Physiological Role ◽  
Skin Inflammation ◽  
Cell Types ◽  
Tnf Receptor ◽  
Ubiquitin Chain ◽  
Regulatory Functions ◽  
Necrosis Factor

The Linear Ubiquitin Assembly Complex (LUBAC), composed of HOIP, HOIL-1L and SHARPIN, promotes Tumor Necrosis Factor (TNF)-dependent NF-kB signaling in diverse cell types. HOIL-1L contains an Npl4 Zinc Finger (NZF) domain that specifically recognizes linear ubiquitin chains, but its physiological role in vivo has remained unclear. Here, we demonstrate that the HOIL-1L NZF domain has important regulatory functions in inflammation and immune responses in mice. We generated knockin mice (Hoil-1lT20;A;R208A/T201A;R208A) expressing a HOIL-1L NZF mutant, and observed attenuated responses to TNF- and LPS-induced shock, including prolonged survival, stabilized body temperature, reduced cytokine production and liver damage markers. Cells derived from the HOIL-1L knockin mice show reduced TNF-dependent NF-kB activation and incomplete recruitment of HOIL-1L into TNF Receptor (TNFR) Complex I. We further show that the HOIL-1L-NZF domain cooperates with SHARPIN to prevent TNFR-dependent skin inflammation. Collectively, our data suggest that linear ubiquitin-chain binding by HOIL-1L regulates immune responses and inflammation in vivo.

Differential effects of lactobacilli on activation and maturation of mouse dendritic cells

2014 ◽  
Vol 5 (3) ◽  
pp. 323-334 ◽  
Author(s):  
I. Elawadli ◽  
J.T. Brisbin ◽  
B.A. Mallard ◽  
M.W. Griffiths ◽  
M. Corredig ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Lactic Acid ◽  
Lactic Acid Bacteria ◽  
Immune Responses ◽  
Inflammatory Cytokine ◽  
Cytokine Production ◽  
Lactobacillus Helveticus ◽  
Inflammatory Cytokine Production

Lactic acid bacteria (LAB) are of interest because of their potential to modulate immune responses. The effects of LAB range from regulation to stimulation of the immune system. A series of studies were performed in vitro to study the effects of six lactic acid bacteria (LAB), Lactobacillus helveticus LH-2, Lactobacillus acidophilus La-5, La-115, La-116 and La-14, and Lactobacillus salivarius, on maturation and activation of mouse dendritic cells. Production of tumour necrosis factor (TNF)-?, interleukin (IL)-6 and IL-10 by dendritic cells (DCs) was determined after treating cells with live LAB. The expression of DC maturation markers, CD80 and CD40, was also measured using flow cytometry after stimulation with LAB. In addition, the expression of Toll-like receptors (TLRs) 2, 4 and 9 by DCs stimulated with LAB was measured. Our results revealed that LAB act differentially on pro-inflammatory and anti-inflammatory cytokine production and induction of co-stimulatory molecules by DCs. Specifically, L. salivarius was found to be the most effective LAB to induce pro-inflammatory cytokine production and expression of co-stimulatory molecules. Moreover, La-14, La-116 and La-5 induced moderate maturation and activation of DCs. On the other hand, LH-2 and La-115 were the least effective lactobacilli to induce DC responses. The present study also revealed that L. salivarius was able to induce the expression of TLR2, 4 and 9 by DCs. In conclusion, various strains and species of LAB can differentially regulate DC activation and maturation, providing further evidence that these bacteria may have the ability to influence and steer immune responses in vivo.

In vitro assessment of the immunomodulatory effects of multispecies probiotic formulations for management of allergic diseases

2011 ◽  
Vol 2 (3) ◽  
pp. 183-192 ◽  
Author(s):  
N.B.M.M. Rutten ◽  
I. Besseling-Van der Vaart ◽  
M. Klein ◽  
S. De Roock ◽  
A. Vlieger ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Cytokine Production ◽  
Allergic Diseases ◽  
Bifidobacterium Lactis ◽  
Beneficial Effects ◽  
Human Mononuclear Cells ◽  
Th2 Cytokine ◽  
Better Than

Modulation of the composition of the intestinal microbiota with probiotics could possibly offer a way of prevention or management of allergic diseases. The objective of this study was to determine the immunomodulating effects of various multispecies probiotic combinations in vitro, as preamble to application in vivo. Multispecies probiotic combinations were formulated and tested for their effects on in vitro cytokine production by human mononuclear cells and were compared to products that already have shown beneficial effects in vivo. All 4 tested combinations of probiotics showed a 40-71% decrease of Th2 cytokine production (IL-4, IL-5, and IL-13) and a variable increase of Th1 (IFN-γ) and Treg cytokine (IL-10) production compared to the medium. A specific probiotic mixture that contained Bifidobacterium breve W25, Bifidobacterium lactis ATCC SD 5219, B. lactis ATCC SD 5220, Lactobacillus plantarum W62, Lactobacillus salivarius W57 and Lactococcus lactis W19 was superior in its stimulating effect on IL-10 production (significant better than the other tested combinations; P=0.001). Modulation of in vitro cytokine production profiles can be used to differentiate between selected probiotic formulations for their immunomodulatory properties. In the future it should be demonstrated whether the immunomodulatory capacities from the multispecies probiotic formulation with the desired profile will be effective in vivo (in adolescents, followed by application in children).

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