scholarly journals Paeoniflorin suppresses inflammatory response in imiquimod-induced psoriasis-like mice and peripheral blood mononuclear cells (PBMCs) from psoriasis patients

2016 ◽  
Vol 94 (8) ◽  
pp. 888-894 ◽  
Author(s):  
Tao Chen ◽  
Li-xin Fu ◽  
Li-wen Zhang ◽  
Bin Yin ◽  
Pei-mei Zhou ◽  
...  
Keyword(s):  
T Cells ◽  
Mouse Model ◽  
Inflammatory Cytokines ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Psoriasis Vulgaris ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α ◽  
Blood Mononuclear Cells

Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders, characterized by hyperproliferation of keratinocytes, dilation and growth of dermal capillary vasculature, and cellular infiltration of T cells, dendritic cells (DCs), and neutrophils. Paeoniflorin (PF), the principal component of total glucosides of paeony (TGP), displays anti-inflammatory and antioxidant properties in several animal models. In this study, we investigated the anti-inflammatory effects and mechanisms of PF in imiquimod (IMQ)-induced psoriasis-like mouse model. The effects of PF on inflammatory cytokine expression in peripheral blood mononuclear cells (PBMCs) from patients with psoriasis vulgaris were also observed. Our results indicated that PF effectively attenuated the clinical and histopathologic changes in IMQ-induced psoriasis-like mouse model. Furthermore, PF reduced the infiltration of T cells, CD11c+DCs, and neutrophils in lesional skin. In addition, PF also significantly decreased the mRNA expression of inflammatory cytokines, such as IL-17, INF-γ, IL-6, and TNF-α, in IMQ-induced psoriasis-like mouse model and PBMCs from patients with psoriasis vulgaris. Hence, our data suggest that PF can inhibit leukocyte infiltration and decrease the expression of inflammatory cytokines such as IL-17, INF-γ, IL-6, and TNF-α. PF might be a candidate drug for the treatment of psoriasis.

scholarly journals Dihydroxylated phenolic acids derived from microbial metabolism reduce lipopolysaccharide-stimulated cytokine secretion by human peripheral blood mononuclear cells

2009 ◽  
Vol 102 (2) ◽  
pp. 201-206 ◽  
Author(s):  
María Monagas ◽  
Nasiruddin Khan ◽  
Cristina Andrés-Lacueva ◽  
Mireia Urpí-Sardá ◽  
Mónica Vázquez-Agell ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Phenolic Acids ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Phenolic Metabolites ◽  
Tnf Α ◽  
Blood Mononuclear Cells ◽  
Pro Inflammatory Cytokines

Oligomers and polymers of flavan-3-ols (proanthocyanidins) are very abundant in the Mediterranean diet, but are poorly absorbed. However, when these polyphenols reach the colon, they are metabolised by the intestinal microbiota into various phenolic acids, including phenylpropionic, phenylacetic and benzoic acid derivatives. Since the biological properties of these metabolites are not completely known, in the present study, we investigated the effect of the following microbial phenolic metabolites: 3,4-dihydroxyphenylpropionic acid (3,4-DHPPA), 3-hydroxyphenylpropionic acid, 3,4-dihydroxyphenylacetic acid (3,4-DHPAA), 3-hydroxyphenylacetic acid, 4-hydroxybenzoic acid and 4-hydroxyhippuric acid (4-HHA), on modulation of the production of the main pro-inflammatory cytokines (TNF-α, IL-1β and IL-6). The production of these cytokines by lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC) pre-treated with the phenolic metabolites was studied in six healthy volunteers. With the exception of 4-HHA for TNF-α secretion, only the dihydroxylated compounds, 3,4-DHPPA and 3,4-DHPAA, significantly inhibited the secretion of these pro-inflammatory cytokines in LPS-stimulated PBMC. Mean inhibition of the secretion of TNF-α by 3,4-DHPPA and 3,4-DHPAA was 84·9 and 86·4 %, respectively. The concentrations of IL-6 in the culture supernatant were reduced by 88·8 and 92·3 % with 3,4-DHPPA and 3,4-DHPAA pre-treatment, respectively. Finally, inhibition was slightly higher for IL-1β, 93·1 % by 3,4-DHPPA and 97·9 % by 3,4-DHPAA. These results indicate that dihydroxylated phenolic acids derived from microbial metabolism present marked anti-inflammatory properties, providing additional information about the health benefits of dietary polyphenols and their potential value as therapeutic agents.

scholarly journals Head to head study of oxelumab and adalimumab in a mouse model of ulcerative colitis based on NOD/Scid IL-2Rγnull mice reconstituted with peripheral blood mononuclear cells

2020 ◽  
pp. dmm.046995
Author(s):  
Henrika Jodeleit ◽  
Paula Winkelmann ◽  
Janina Caesar ◽  
Sebastian Sterz ◽  
Lesca M. Holdt ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
T Cells ◽  
Mouse Model ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Serum Levels ◽  
Peripheral Blood Mononuclear ◽  
Significant Difference ◽  
Blood Mononuclear Cells

The goal of this study was to demonstrate that the combination of patient immune profiling and testing in a humanized mouse model of ulcerative colitis (UC) may lead to patient stratification for treatment with oxelumab. First, immunological profiles of UC patients and non-UC donors were analyzed for CD4+ T cells expressing OX40 (CD134) and CD14+ monocytes expressing OX40L (CD252) by flow cytometric analysis. A significant difference was observed between both groups for CD14+ OX40L+ (UC: n=11, 85.44±21.17; mean±sd, non-UC: n=5, 30.7±34.92; p=0.02), no significant difference was detected for CD4+ OX40+. CD14+ OX40L+ monocytes correlated significantly with TH1 and TH2 cells. Secondly, NOD/Scid IL2-Rgamma null mice were reconstituted with peripheral blood mononuclear cells from UC donors exhibiting elevated levels of OX40L, and the efficacy of oxelumab was compared to that of adalimumab. Read out were the clinical, colon, andhistological scores, and serum levels of IL-6, IL-1ß and glutamic acid. Treatment with oxelumab or adalimumab resulted in significantly reduced clinical, colon, and histological scores, reduced serum levels of IL-6 and reduced frequencies of splenic human effector memory T cells and switched B cells. Comparison of efficacy of adalimumab and oxelumab by orthogonal partial least square discrimination analysis revealed that oxelumab was slightly superior to adalimumab, however, elevated serum levels of glutamic acid suggested ongoing inflammation. These results suggest that oxelumab addresses the pro-inflammatory arm of inflammation while promoting the remodeling arm and that patients exhibiting elevated levels of OX40L may benefit from treatment with oxelumab. Keywords: Ulcerative colitis, NOD/Scid IL2-Rγnull, NSG, anti-CD252 antibodies, oxelumab, inflammatory bowel disease

scholarly journals Expression of barrier proteins in the skin lesions and inflammatory cytokines in peripheral blood mononuclear cells of atopic dogs

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sarita Kanwal ◽  
Shanker K. Singh ◽  
Sandeep P. Soman ◽  
Soumen Choudhury ◽  
Priyambada Kumari ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Cytokines ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Skin Barrier ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α ◽  
Blood Mononuclear Cells ◽  
Healthy Dogs

AbstractAtopic dermatitis (AD) is one of the most common skin diseases of dogs. Defects in the skin barrier and overproduction of inflammatory cytokines may be the pathogenesis of canine AD. Therefore, the present study was aimed to quantify the gene expression of certain skin barrier proteins and inflammatory cytokines in dogs with AD. Eleven dogs with AD and three healthy dogs were included in the present study. The skin barrier proteins, namely Filaggrin (FLG) and Involucrin (IVL), gene expression was quantified by Real-time PCR in the lesional skin tissues of the atopic dogs and normal skin of the healthy dogs. In addition to the skin proteins, the gene expressions of the interleukin (IL)-13, IL-31, and tumour necrosis factor (TNF)-α were also quantified in the peripheral blood mononuclear cells (PBMCs) of these dogs. Compared to the healthy dogs, significantly higher (P ≤ 0.01) FLG gene expression and significantly (P ≤ 0.05) lower expression of the IVL gene were quantified in the skin of atopic dogs. Further, the dogs with AD revealed significantly higher expression of TNF-α (P ≤ 0.01), IL-31 (P ≤ 0.05), and IL-13 (P ≤ 0.05) as compared to the healthy dogs. The findings of our present study evidently suggest significantly increased and decreased expressions of FLG and IVL genes, respectively, which may be responsible for disruption of the skin barrier in dogs with AD. While, the over-expressions of TNF-α, IL-31, and IL-13 genes might be attributed to the clinical pathology and manifestations of AD in dogs. However, further studies are warranted to substantiate our hypothesis about pathogenesis and clinical manifestation of AD in dogs by including a large number of animals.

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