scholarly journals Ribes nigrum Leaf Extract Preferentially Inhibits IFN-γ-Mediated Inflammation in HaCaT Keratinocytes

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 3044
Author(s):  
Andrea Magnavacca ◽  
Stefano Piazza ◽  
Anna Cammisa ◽  
Marco Fumagalli ◽  
Giulia Martinelli ◽  
...  
Keyword(s):  
Leaf Extract ◽  
Inflammatory Diseases ◽  
Ribes Nigrum ◽  
Leaf Extracts ◽  
Traditional Use ◽  
Independent Manner ◽  
Beneficial Effects ◽  
Tnf Α ◽  
Cytokine Milieu ◽  
Ifn Γ

Ribes nigrum L. (blackcurrant) leaf extracts, due to high levels of flavonols and anthocyanins, have been shown to exhibit beneficial effects in inflammatory diseases. However, whereas their traditional use has been investigated and validated in several models of inflammation and oxidative stress, the possible impact on skin disorders is still largely unknown. The purpose of this work was to elucidate the effects of R. nigrum leaf extract (RNLE) on keratinocyte-derived inflammatory mediators, elicited by a Th1 or Th2 cytokine milieu. HaCaT cells were challenged with TNF-α, either alone or in combination with the costimulatory cytokines IFN-γ or IL-4, and the release of proinflammatory cytokines and mediators (IL-8, IL-6, s-ICAM-1, and TSLP) was evaluated. The results showed that RNLE preferentially interferes with IFN-γ signaling, demonstrating only negligible activity on TNF-α or IL-4. This effect was attributed to flavonols, which might also account for the ability of RNLE to impair TNF-α/IL-4-induced TSLP release in a cAMP-independent manner. These results suggest that RNLE could have an antiallergic effect mediated in keratinocytes via mechanisms beyond histamine involvement. In conclusion, the discovery of RNLE preferential activity against IFN-γ-mediated inflammation suggests potential selectivity against Th1 type response and the possible use in Th1 inflammatory diseases.

scholarly journals Skullcapflavone II Suppresses TNF-α/IFN-γ-Induced TARC, MDC, and CTSS Production in HaCaT Cells

2021 ◽  
Vol 22 (12) ◽  
pp. 6428
Author(s):  
Hanon Lee ◽  
Dong Hun Lee ◽  
Jang-Hee Oh ◽  
Jin Ho Chung
Keyword(s):  
P38 Mapk ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Mapk Signaling ◽  
Hacat Cells ◽  
Protein Levels ◽  
Tnf Α ◽  
Ifn Γ ◽  
Mapk Signaling Pathways ◽  
Pro Inflammatory Cytokines

Skullcapflavone II (SFII), a flavonoid derived from Scutellaria baicalensis, has been reported to have anti-inflammatory properties. However, its therapeutic potential for skin inflammatory diseases and its mechanism are unknown. Therefore, this study aimed to investigate the effect of SFII on TNF-α/IFN-γ-induced atopic dermatitis (AD)-associated cytokines, such as thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC). Co-stimulation with TNF-α/IFN-γ in HaCaT cells is a well-established model for induction of pro-inflammatory cytokines. We treated cells with SFII prior to TNF-α/IFN-γ-stimulation and confirmed that it significantly inhibited TARC and MDC expression at the mRNA and protein levels. Additionally, SFII also inhibited the expression of cathepsin S (CTSS), which is associated with itching in patients with AD. Using specific inhibitors, we demonstrated that STAT1, NF-κB, and p38 MAPK mediate TNF-α/IFN-γ-induced TARC and MDC, as well as CTSS expression. Finally, we confirmed that SFII significantly suppressed TNF-α/IFN-γ-induced phosphorylation of STAT1, NF-κB, and p38 MAPK. Taken together, our study indicates that SFII inhibits TNF-α/IFN-γ-induced TARC, MDC, and CTSS expression by regulating STAT1, NF-κB, and p38 MAPK signaling pathways.

scholarly journals Role of Th22 Cells in the Pathogenesis of Autoimmune Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Qi Jiang ◽  
Guocan Yang ◽  
Fan Xiao ◽  
Jue Xie ◽  
Shengjun Wang ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Chemokine Receptors ◽  
Inflammatory Diseases ◽  
Biological Effects ◽  
Cell Subset ◽  
Interferon Γ ◽  
Th22 Cells ◽  
Tnf Α ◽  
Ifn Γ

Upon antigenic stimulation, naïve CD4+T cells differentiate into different subsets and secrete various cytokines to exert biological effects. Th22 cells, a newly identified CD4+T cell subset,are distinct from the Th1, Th2 and Th17 subsets. Th22 cells secrete certain cytokines such as IL-22, IL-13 and TNF-α, but not others, such as IL-17, IL-4, or interferon-γ (IFN-γ), and they express chemokine receptors CCR4, CCR6 and CCR10. Th22 cells were initially found to play a role in skin inflammatory diseases, but recent studies have demonstrated their involvement in the development of various autoimmune diseases. Here, we review research advances in the origin, characteristics and effector mechanisms of Th22 cells, with an emphasis on the role of Th22 cells and their main effector cytokine IL-22 in the pathogenesis of autoimmune diseases. The findings presented here may facilitate the development of new therapeutic strategies for targeting these diseases.

scholarly journals Inhibitory Effects of Luteolin 7-Methyl Ether Isolated from Wikstroemia ganpi on Tnf-A/Ifn-Γ Mixture-Induced Inflammation in Human Keratinocyte

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4387
Author(s):  
Jonghwan Jegal ◽  
Tae-Young Kim ◽  
No-June Park ◽  
Beom-Geun Jo ◽  
Geon-A. Jo ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Methyl Ether ◽  
Therapeutic Agent ◽  
Inflammatory Diseases ◽  
Hacat Cells ◽  
Inhibitory Effects ◽  
Gm Csf ◽  
Human Keratinocyte ◽  
Tnf Α ◽  
Ifn Γ

Plants of the genus Wikstroemia are traditionally used in China to treat various inflammatory diseases. The purpose of this study was to isolate the components of Wikstroemia ganpi (Siebold & Zucc.) Maxim., to evaluate their anti-atopic activities and to identify candidates with anti-atopic therapeutics. A total of 24 compounds were isolated by bioassay-guided separation, including one novel compound, which was tilianin 5-methyl ether. The anti-atopic activities of the isolated compounds were determined using TNF-α-treated RBL-2H3 cells and HaCaT cells. The mRNA expressions of IL-4, IL-6, GM-CSF, G-CSF and TRPV1 were reduced by luteolin 7-methyl ether. The study shows that the luteolin 7-methyl ether isolated from W. ganpi is a potential therapeutic agent for the treatment of atopic dermatitis.

scholarly journals IFN-γ and TNF-α drive a CXCL10+ CCL2+ macrophage phenotype expanded in severe COVID-19 and other diseases with tissue inflammation

2020 ◽  
Author(s):  
Fan Zhang ◽  
Joseph R. Mears ◽  
Lorien Shakib ◽  
Jessica I. Beynor ◽  
Sara Shanaj ◽  
...  
Keyword(s):  
Immune Cell ◽  
Ex Vivo ◽  
Inflammatory Diseases ◽  
Macrophage Phenotype ◽  
Tnf Α ◽  
Key Driver ◽  
Ifn Γ ◽  
Immunomodulatory Therapies ◽  
Disease Analysis ◽  
Inflammatory Macrophage

AbstractImmunosuppressive and anti-cytokine treatment may have a protective effect for patients with COVID-19. Understanding the immune cell states shared between COVID-19 and other inflammatory diseases with established therapies may help nominate immunomodulatory therapies. Using an integrative strategy, we built a reference by meta-analyzing > 300,000 immune cells from COVID-19 and 5 inflammatory diseases including rheumatoid arthritis (RA), Crohn’s disease (CD), ulcerative colitis (UC), lupus, and interstitial lung disease. Our cross-disease analysis revealed that an FCN1+ inflammatory macrophage state is common to COVID-19 bronchoalveolar lavage samples, RA synovium, CD ileum, and UC colon. We also observed that a CXCL10+ CCL2+ inflammatory macrophage state is abundant in severe COVID-19, inflamed CD and RA, and expresses inflammatory genes such as GBP1, STAT1, and IL1B. We found that the CXCL10+ CCL2+ macrophages are transcriptionally similar to blood-derived macrophages stimulated with TNF-α and IFN-γ ex vivo. Our findings suggest that IFN-γ, alongside TNF-α, might be a key driver of this abundant inflammatory macrophage phenotype in severe COVID-19 and other inflammatory diseases, which may be targeted by existing immunomodulatory therapies.

scholarly journals Differential CD147 Functional Epitopes on Distinct Leukocyte Subsets

2021 ◽  
Vol 12 ◽  
Author(s):  
Supansa Pata ◽  
Sirirat Surinkaew ◽  
Nuchjira Takheaw ◽  
Witida Laopajon ◽  
Kantinan Chuensirikulchai ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cell Function ◽  
Inflammatory Diseases ◽  
Cell Contact ◽  
Cell Functions ◽  
Tnf Α ◽  
Ifn Γ

CD147, a member of the immunoglobulin (Ig) superfamily, is widely expressed in several cell types. CD147 molecules have multiple cellular functions, such as migration, adhesion, invasion, energy metabolism and T cell activation. In particular, recent studies have demonstrated the potential application of CD147 as an effective therapeutic target for cancer, as well as autoimmune and inflammatory diseases. In this study, we elucidated the functional epitopes on CD147 extracellular domains in T cell regulation using specific monoclonal antibodies (mAbs). Upon T cell activation, the anti-CD147 domain 1 mAbs M6-1E9 and M6-1D4 and the anti-CD147 domain 2 mAb MEM-M6/6 significantly reduced surface expression of CD69 and CD25 and T cell proliferation. To investigate whether functional epitopes of CD147 are differentially expressed on distinct leukocyte subsets, PBMCs, monocyte-depleted PBMCs and purified T cells were activated in the presence of anti-CD147 mAbs. The mAb M6-1E9 inhibited T cell functions via activation of CD147 on monocytes with obligatory cell-cell contact. Engagement of the CD147 epitope by the M6-1E9 mAb downregulated CD80 and CD86 expression on monocytes and IL-2, TNF-α, IFN-γ and IL-17 production in T cells. In contrast, the mAb M6-1D4 inhibited T cell function via activation of CD147 on T cells by downregulating IL-2, TNF-α and IFN-γ. Herein, we demonstrated that certain epitopes of CD147, expressed on both monocytes and T cells, are involved in the regulation of T cell activation.

scholarly journals Antimalarial Activity of Meriandra dianthera Leaf Extracts in Plasmodium berghei-Infected Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Kalay Hagazy ◽  
Gereziher G. Sibhat ◽  
Aman Karim ◽  
Gebretsadkan H. Tekulu ◽  
Gomathi Periasamy ◽  
...  
Keyword(s):  
Plasmodium Berghei ◽  
Leaf Extract ◽  
Antimalarial Activity ◽  
Negative Control ◽  
Mice Model ◽  
Oral Toxicity ◽  
Leaf Extracts ◽  
Traditional Use ◽  
Crude Leaf Extract

Objective. To evaluate the antimalarial effect of aqueous methanolic extract and solvent fractions of Meriandra dianthera leaves against Plasmodium berghei in mice model. Method. M. dianthera leaves were extracted with 80% methanol and dried. The dried crude extract was then defatted and further fractionated with chloroform, ethyl acetate, and butanol. Acute oral toxicity test was performed as per the Organization for Economic Cooperation and Development guideline 425. Peter’s 4-day suppressive test was used to determine the in vivo antimalarial activity of the extract and fractions. Result. The crude leaf extract of Meriandra dianthera showed parasite inhibition of 42.28% and 45.52% at doses of 400 and 600 mg/kg, respectively, as compared to the negative control. Moreover, the mice which received chloroform and aqueous fractions at the dose of 400 mg/kg/day showed significant (P<0.001) chemosuppression compared to the negative control. Both the extract and fractions were able to prevent P. berghei induced body weight loss and body temperature reduction and also increased the survival time of the mice as compared to the negative control. The aqueous methanolic leaf extract of M. dianthera showed no gross signs of toxicity or mortality in mice until a single oral dose of 2000 mg/kg. Conclusion. The extracts of M. dianthera leaves showed promising antimalarial activity, with no sign of toxicity and therefore may support its traditional use for the treatment of malaria.

scholarly journals Cytokines Differently Define the Immunomodulation of Mesenchymal Stem Cells from the Periodontal Ligament

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1222 ◽  
Author(s):  
Christian Behm ◽  
Alice Blufstein ◽  
Johannes Gahn ◽  
Michael Nemec ◽  
Andreas Moritz ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Lymphocytes ◽  
Periodontal Ligament ◽  
Periodontal Ligament Stem Cells ◽  
T Lymphocyte Proliferation ◽  
Tnf Α ◽  
Proliferation And Apoptosis ◽  
Cytokine Milieu ◽  
Ifn Γ

Human periodontal ligament stem cells (hPDLSCs) play an important role in periodontal tissue homeostasis and regeneration. The function of these cells in vivo depends largely on their immunomodulatory ability, which is reciprocally regulated by immune cells via cytokines, particularly interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β. Different cytokines activate distinct signaling pathways and might differently affect immunomodulatory activities of hPDLSCs. This study directly compared the effect of IFN-γ, TNF-α, or IL-1β treated primary hPDLSCs on allogenic CD4+ T lymphocyte proliferation and apoptosis in an indirect co-culture model. The effects of IFN-γ, TNF-α, and IL-1β on the expression of specific immunomodulatory factors such as intoleamine-2,3-dioxygenase-1 (IDO-1), prostaglandin E2 (PGE2), and programmed cell death 1 ligand 1 (PD-L1) and ligand 2 (PD-L2) in hPDLSCs were compared. The contribution of different immunomodulatory mediators to the immunomodulatory effects of hPDLSCs in the indirect co-culture experiments was assessed using specific inhibitors. Proliferation of CD4+ T lymphocytes was inhibited by hPDLSCs, and this effect was strongly enhanced by IFN-γ and IL-1β but not by TNF-α. Apoptosis of CD4+ T lymphocytes was decreased by hPDLSCs per se. This effect was counteracted by IFN-γ or IL-1β. Additionally, IFN-γ, TNF-α, and IL-1β differently regulated all investigated immunomediators in hPDLSCs. Pharmacological inhibition of immunomediators showed that their contribution in regulating CD4+ T lymphocytes depends on the cytokine milieu. Our data indicate that inflammatory cytokines activate specific immunomodulatory mechanisms in hPDLSCs and the expression of particular immunomodulatory factors, which underlies a complex reciprocal interaction between hPDLSCs and CD4+ T lymphocytes.

scholarly journals Chitosan Protects Immunosuppressed Mice Against Cryptosporidium parvum Infection Through TLR4/STAT1 Signaling Pathways and Gut Microbiota Modulation

2022 ◽  
Vol 12 ◽  
Author(s):  
Sajid Ur Rahman ◽  
Haiyan Gong ◽  
Rongsheng Mi ◽  
Yan Huang ◽  
Xiangan Han ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Signaling Pathways ◽  
Cryptosporidium Parvum ◽  
Basal Diet ◽  
Sequencing Analysis ◽  
Beneficial Effects ◽  
Tnf Α ◽  
Stat1 Signaling ◽  
Ifn Γ ◽  
Immunosuppressed Mice

Cryptosporidium parvum infection is very common in infants, immunocompromised patients, or in young ruminants, and chitosan supplementation exhibits beneficial effects against the infection caused by C. parvum. This study investigated whether chitosan supplementation modulates the gut microbiota and mediates the TLR4/STAT1 signaling pathways and related cytokines to attenuate C. parvum infection in immunosuppressed mice. Immunosuppressed C57BL/6 mice were divided into five treatment groups. The unchallenged mice received a basal diet (control), and three groups of mice challenged with 1 × 106 C. parvum received a basal diet, a diet supplemented with 50 mg/kg/day paromomycin, and 1 mg/kg/day chitosan, and unchallenged mice treated with 1 mg/kg/day chitosan. Chitosan supplementation regulated serum biochemical indices and significantly (p &lt; 0.01) reduced C. parvum oocyst excretion in infected mice treated with chitosan compared with the infected mice that received no treatment. Chitosan-fed infected mice showed significantly (p &lt; 0.01) decreased mRNA expression levels of interferon-gamma (IFN-γ) and tumor necrosis factor-α (TNF-α) compared to infected mice that received no treatment. Chitosan significantly inhibited TLR4 and upregulated STAT1 protein expression (p &lt; 0.01) in C. parvum-infected mice. 16S rRNA sequencing analysis revealed that chitosan supplementation increased the relative abundance of Bacteroidetes/Bacteroides, while that of Proteobacteria, Tenericutes, Defferribacteres, and Firmicutes decreased (p &lt; 0.05). Overall, the findings revealed that chitosan supplementation can ameliorate C. parvum infection by remodeling the composition of the gut microbiota of mice, leading to mediated STAT1/TLR4 up- and downregulation and decreased production of IFN-γ and TNF-α, and these changes resulted in better resolution and control of C. parvum infection.

scholarly journals Shikonin ameliorates Experimental Autoimmune Encephalomyelitis (EAE) via Immuno-modulatory, anti-apototic, and anti-oxidative activity

2020 ◽  
Author(s):  
Mehrdad Nasrollahzadeh Sabet ◽  
Sajjad Biglari ◽  
Emran Esmaeilzadeh
Keyword(s):  
Multiple Sclerosis ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Inflammatory Diseases ◽  
Expression Level ◽  
Autoimmune Encephalomyelitis ◽  
Glutathione Peroxidase 1 ◽  
Tnf Α ◽  
Ifn Γ ◽  
Underlying Mechanisms ◽  
Experimental Autoimmune

Abstract Background Multiple sclerosis is a common auto-immuno-inflammatory diseases of the central nervous system in adults. There are several underlying mechanisms for pathogenesis of the disease, including inflammation, oligodendrocyte apoptosis, and oxidative stress. Methods We have investigated the mechanism of Shikonin action in C57BL/6 experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. Results Our results revealed that EAE induction significantly increased the extent of demyelination in the corpus callosum tissues of the animals, while treatment of the mice with Shikonin, significantly decreased the extent of demyelination. Real-time PCR based analyzing the brain samples from the EAE mice, revealed a significant enhancement in the expression level of TNF-α , IFN-γ and Bax genes as well as a reduction in the expression level of TGF-β and Bcl2. Shikonin treatment significantly reduced the expression level of TNF-α , IFN-γ and Bax. On the other hand, the expression levels of TGF-β and Bcl2 as well as the Glutathione peroxidase-1 (GPX-1) enzyme were significantly increased following Shikonin treatment. Conclusion This study emphasizes the immune-modulatory, anti-apoptotic, and anti-oxitive effects of Shikonin, which may have an important healing influence on the severity of EAE.

Phytic acid modulates the morphology, immunological response of cytokines and β-defensins in porcine intestine exposed to deoxynivalenol and fumonisin B1

2021 ◽  
pp. 1-10
Author(s):  
E.O. da Silva ◽  
J.P. Santos ◽  
A.T. Morey ◽  
L.M. Yamauchi ◽  
A.P.F.R. Loureiro Bracarense
Keyword(s):  
Phytic Acid ◽  
Morphological Changes ◽  
Animal Health ◽  
Fumonisin B1 ◽  
Immunological Response ◽  
Beneficial Effects ◽  
Intestinal Lesions ◽  
Tnf Α ◽  
Ifn Γ ◽  
Necrosis Factor

Occurrence of mycotoxins in agricultural products represents a risk for human and animal health. Therefore, there is a requirement of strategies to mitigate their harmful impacts. This study investigated the effects of phytic acid (IP6) on the immunological response of pro-(interleukin (IL)-1β, IL-6, IL-8, IL-10, interferon (IFN)-γ, tumour necrosis factor (TNF)-α) and anti-inflammatory (IL-10) cytokines and β-defensins 1 (pBD-1) and 2 (pBD-2) in porcine jejunal explants exposed to deoxynivalenol (DON) and fumonisin B1 (FB1). The explants were exposed to the following treatments: control, DON (10 μM), DON plus IP6 2.5 mM or 5 mM, FB1 (70 μM), FB1 IP6 plus 2.5 or 5 mM. The expression levels of the cytokines were measured by RT-qPCR. The exposure to FB1 and DON induced intestinal lesions. The presence of 2.5 and 5 mM IP6 inhibited the morphological changes induced by the mycotoxins. The explants exposed to DON showed an increase in the expression of IL-1β and IL-8 and a decrease in the levels of IL-6, IFN-γ, IL-10 and pBD-2. IP6 (5 mM) decreased the expression of IL-8 and increased the expression in pBD-1 and 2 compared to DON alone. FB1 induced a significant decrease in the levels of most of the pro-inflammatory cytokines, IL-10 and pBD-1, and an increase in IL-1β expression. The addition of IP6 5 mM induced significant increase in TNF-α expression compared to FB1. Taken together, the results suggest IP6 modulates immunological changes induced by DON and FB1 on intestinal mucosa resulting in beneficial effects that contribute to intestinal homeostasis and health.

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