The therapeutic promises of Lianhuaqingke in the mice model of coronavirus pneumonia (HCoV-229E and SARS-CoV-2)

Abstract Background Lianhuaqingke (LHQK) has been approved for the treatment of acute tracheobronchitis and exerts a broad-spectrum antiviral effect in our previous study. Methods Acute pneumonia caused by HCoV-229E was modeled in BALB/c mice. The anti-viral effect of LHQK was assessed by measuring the lung index and virus titer of lung tissues. The expression levels of pro-inflammatory cytokines in lung tissues and peripheral blood were measured by ELISA. The morphological changes of lung tissues were observed by H&E staining. The subsets of Th cells were assayed by the flow cytometry, including Th0, Th1, Th2, Treg, and Th17. The expression level of MUC5AC in 16HBE cells treated with TNFα was measured by ELISA. Immunofluorescence staining for β-IV tubulin was used to identify the airway epithelial ciliary in the condition-cultured RTE cells treated with TNFα. The direct antiviral effect of LHQK was assessed in vitro in Vero E6 infected by SARS-CoV-2, validated in vivo in the COVID-19 model of hACE2 transgenic mouse by detecting the lung index, the SARS-CoV-2 virus load, and the morphological changes of lung tissues. Results LHQK reduced the weight loss and the lung index by inhibiting the HCoV-229E replication and reducing the expression of pro-inflammatory cytokines in lung tissues. An assay for the Th cell subsets in peripheral blood revealed that LHQK could reduce the ratio of Th1/Th2 and increase the Treg/Th17 ratio in a dose-dependent way, which indicated that LHQK could coordinate the Th-mediated immune responses against the virus. In in vitro injury by TNFα, LHQK inhibited MUC5AC expression in 16HBE cells and increased the number of β-IV tubulin positive staining cells in the condition-cultured RTE cells. In the SARS-CoV-2-infected mice, LHQK could reduce weight loss, inhibit viral replication, and alleviate lung tissue damage. Conclusions Our results demonstrate that LHQK exerts therapeutic effects on pneumonia caused by HCoVs (HCoV-229E and SARS-CoV-2) in mice, and that the anti-HCoV effects might depend on its immunomodulatory capacities. All these results suggest that LHQK serves as a potential adjuvant for anti-HCoV therapies.

Download Full-text

Sa1782 Peripheral Blood CD4+ T-Lymphocytes From Crohn's Disease Patients Demonstrate Hyper-Responses to PRO-Inflammatory Cytokines In Vitro by Generating IL-17/FOXP3 Double Expressing Sub-Population

Gastroenterology ◽

10.1016/s0016-5085(13)61093-8 ◽

2013 ◽

Vol 144 (5) ◽

pp. S-305

Author(s):

Aito Ueno ◽

Humberto Jijon ◽

Kim Ford ◽

Ronald Chan ◽

Paul L. Beck ◽

...

Keyword(s):

Crohn’S Disease ◽

T Lymphocytes ◽

Crohn's Disease ◽

Inflammatory Cytokines ◽

Peripheral Blood ◽

Pro Inflammatory Cytokines

Download Full-text

Methylmercury-induced pro-inflammatory cytokines activation and its preventive strategy using anti-inflammation N-acetyl-l-cysteine: a mini-review

Reviews on Environmental Health ◽

10.1515/reveh-2020-0026 ◽

2020 ◽

Vol 35 (3) ◽

pp. 233-238

Author(s):

Muflihatul Muniroh

Keyword(s):

Inflammatory Cytokines ◽

Health Concern ◽

Brain Cells ◽

Preventive Strategy ◽

Hearing Impairments ◽

Sensory Disturbances ◽

Anti Inflammation ◽

Pro Inflammatory Cytokines

AbstractThe exposure of methylmercury (MeHg) has become a public health concern because of its neurotoxic effect. Various neurological symptoms were detected in Minamata disease patients, who got intoxicated by MeHg, including paresthesia, ataxia, gait disturbance, sensory disturbances, tremors, visual, and hearing impairments, indicating that MeHg could pass the blood-brain barrier (BBB) and cause impairment of neurons and other brain cells. Previous studies have reported some expected mechanisms of MeHg-induced neurotoxicity including the neuroinflammation pathway. It was characterized by the up-regulation of numerous pro-inflammatory cytokines expression. Therefore, the use of anti-inflammatories such as N-acetyl-l-cysteine (NAC) may act as a preventive compound to protect the brain from MeHg harmful effects. This mini-review will explain detailed information on MeHg-induced pro-inflammatory cytokines activation as well as possible preventive strategies using anti-inflammation NAC to protect brain cells, particularly in in vivo and in vitro studies.

Download Full-text

Cladribine inhibits secretion of pro-inflammatory cytokines and phagocytosis in human monocyte-derived M1 macrophages in-vitro

International Immunopharmacology ◽

10.1016/j.intimp.2020.107270 ◽

2021 ◽

Vol 91 ◽

pp. 107270

Author(s):

Caroline B.K. Mathiesen ◽

Asha M. Rudjord-Levann ◽

Monika Gad ◽

Jesper Larsen ◽

Finn Sellebjerg ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Human Monocyte ◽

M1 Macrophages ◽

Pro Inflammatory Cytokines

Download Full-text

Silica nanoparticles induce NLRP3 inflammasome activation in human primary immune cells

Innate Immunity ◽

10.1177/1753425917738331 ◽

2017 ◽

Vol 23 (8) ◽

pp. 697-708 ◽

Cited By ~ 19

Author(s):

Diana M Gómez ◽

Silvio Urcuqui-Inchima ◽

Juan C Hernandez

Keyword(s):

Physicochemical Properties ◽

Silica Nanoparticles ◽

Inflammatory Cytokines ◽

Nlrp3 Inflammasome ◽

Deep Understanding ◽

Inflammasome Activation ◽

Dependent Manner ◽

Dose Dependent ◽

Pro Inflammatory Cytokines

In recent years, the potential use of silica nanoparticles (SiNPs) among different biomedical fields has grown. A deep understanding of the physicochemical properties of nanoparticles (NPs) and their regulation of specific biological responses is crucial for the successful application of NPs. Exposure to NP physicochemical properties (size, shape, porosity, etc.) could result in deleterious effects on cellular functions, including a pro-inflammatory response mediated via activation of the NLRP3 inflammasome. The aim of this study was to evaluate the potential in vitro immunomodulatory effect of 12-nm and 200-nm SiNPs on the expression of pro-inflammatory cytokines and NLRP3 inflammasome components in human primary neutrophils and PBMCs. This study demonstrates that regardless of the size of the nanoparticles, SiNPs induce the production of pro-inflammatory cytokines in a dose-dependent manner. Induced IL-1β production after exposure to SiNPs suggests the involvement of NLRP3 inflammasome components participation in this process. In conclusion, SiNPs induce the production of pro-inflammatory cytokines in a dose-dependent manner. Furthermore, our data suggest that the production and release of IL-1β possibly occurs through the formation of the NLRP3 inflammasome.

Download Full-text

Human umbilical cord mesenchymal stem cell-derived extracellular vesicles attenuate experimental autoimmune encephalomyelitis via regulating pro and anti-inflammatory cytokines

Scientific Reports ◽

10.1038/s41598-021-91291-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Samira Ahmadvand Koohsari ◽

Abdorrahim Absalan ◽

Davood Azadi

Keyword(s):

Spinal Cord ◽

Body Weight ◽

Extracellular Vesicles ◽

Inflammatory Cytokines ◽

Clinical Score ◽

Human Umbilical Cord ◽

Therapeutic Effects ◽

Leukocyte Infiltration ◽

Anti Inflammatory ◽

Pro Inflammatory Cytokines

AbstractThe therapeutic effects of mesenchymal stem cells-extracellular vesicles have been proved in many inflammatory animal models. In the current study, we aimed to investigate the effect of extracellular vesicles (EVs) derived from human umbilical cord-MSC (hUCSC-EV) on the clinical score and inflammatory/anti-inflammatory cytokines on the EAE mouse model. After induction of EAE in C57Bl/6 mice, they were treated intravenously with hUCSC-EV or vehicle. The clinical score and body weight of all mice was registered every day. On day 30, mice were sacrificed and splenocytes were isolated for cytokine assay by ELISA. Cytokine expression of pro-/anti-inflammatory cytokine by real-time PCR, leukocyte infiltration by hematoxylin and eosin (H&E) staining, and the percent of glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) positive cells by immunohistochemistry were assessed in the spinal cord. Our results showed that hUCSC-EV-treated mice have lower maximum mean clinical score (MMCS), pro-inflammatory cytokines, and inflammatory score in comparison to the control mice. We also showed that hUCSC-EV administration significantly improved body weight and increased the anti-inflammatory cytokines and the frequency of Treg cells in the spleen. There was no significant difference in the percent of GFAP and MBP positive cells in the spinal cord of experimental groups. Finally, we suggest that intravenous administration of hUCSC-EV alleviate induce-EAE by reducing the pro-inflammatory cytokines, such as IL-17a, TNF-α, and IFN-γ, and increasing the anti-inflammatory cytokines, IL-4 and IL-10, and also decrease the leukocyte infiltration in a model of MS. It seems that EVs from hUC-MSCs have the same therapeutic effects similar to EVs from other sources of MSCs, such as adipose or bone marrow MSCs.

Download Full-text

The protective effects of carvacrol and thymol against paracetamol–induced toxicity on human hepatocellular carcinoma cell lines (HepG2)

Human & Experimental Toxicology ◽

10.1177/0960327115627688 ◽

2016 ◽

Vol 35 (12) ◽

pp. 1252-1263 ◽

Cited By ~ 23

Author(s):

SS Palabiyik ◽

E Karakus ◽

Z Halici ◽

E Cadirci ◽

Y Bayir ◽

...

Keyword(s):

Oxidative Stress ◽

Inflammatory Cytokines ◽

Hepg2 Cells ◽

Folk Medicine ◽

Hepatoprotective Activity ◽

High Dose ◽

Protective Effects ◽

And Oxidative Stress ◽

Pro Inflammatory Cytokines

Acetaminophen (APAP) overdose could induce liver damage and lead to acute liver failure. The treatment of APAP overdoses could be improved by new therapeutic strategies. Thymus spp., which has many beneficial effects and has been used in folk medicine, is one such potential strategy. In the present study, the hepatoprotective activity of the main constituents of Thymus spp., carvacrol and thymol, were evaluated in light of APAP-induced hepatotoxicity. We hoped to understand the hepatoprotective mechanism of these agents on the antioxidant system and pro-inflammatory cytokines in vitro. Dose-dependent effects of thymol and carvacrol (25, 50, and 100 µM) were tested on cultured HepG2 cells. N-Acetylcysteine (NAC) was tested as positive control. We showed that APAP inhibited HepG2 cell growth by inducing inflammation and oxidative stress. Incubating APAP-exposed HepG2 cells with carvacrol and thymol for 24 h ameliorated this inflammation and oxidative stress. We also evaluated alanine transaminase and lactate dehydrogenase levels of HepG2 cells. We found that thymol and carvacrol protected against APAP-induced toxicity in HepG2 cells by increasing antioxidant activity and reducing pro-inflammatory cytokines, such as tumor necrosis factor α and interleukin 1β. Taking together high-dose thymol and carvacrol treatment has an effect close to NAC treatment in APAP toxicity, but thymol has better treatment effect than carvacrol.

Download Full-text

EFFECT OF EXOPOLISACCHARIDES OF LACTIC ACID BACTERIA ON THE SYNTHESIS OF PROINFLAMMATORY CYTOKINES BY MACROPHAGIC MICE IN PHAGOCYTOSIS OF STAPHYLOCOCCUS AUREUS

Journal of microbiology epidemiology immunobiology ◽

10.36233/0372-9311-2018-1-67-71 ◽

2018 ◽

pp. 67-71

Author(s):

G. T. Uryadova ◽

E. A. Gorelnikova ◽

N. A. Fokina ◽

A. S. Dolmashkina ◽

L. V. Karpunina

Keyword(s):

Staphylococcus Aureus ◽

Lactic Acid ◽

Lactic Acid Bacteria ◽

Lactococcus Lactis ◽

Inflammatory Cytokines ◽

Proinflammatory Cytokines ◽

Streptococcus Thermophilus ◽

Ambiguous Effect ◽

Pro Inflammatory Cytokines

Aim. Study of the effect of exopolysaccharides (EPS) of lactic acid cocci on cytokine activity of macrophages of mice with phagocytosis in vitro Staphylococcus aureus 209-P. Materials and methods. The EPS of Streptococcus thermophilus and Lactococcus lactis B-1662 was used in the work. At 13, 5 and 7, AMP and PMP were isolated and the phagocytosis process was modeled in vitro. After 30 minutes, 1, 6 and 24 hours, the content of pro-inflammatory cytokines IL-1a and TNF-a was determined. Results. EPSs had an ambiguous effect on the production of cytokines. The greatest effect on the synthesis was provided by EPS of S. thermophilus. Conclusion. The results of the study allow us to talk about the possibility of using EPS of S. thermophilus as a preventive immunomodulator for correction of the cytokine status of animals.

Download Full-text

Macrophage-Biomimetic Porous Se@SiO2 Nanocomposites For “Dual Model” Immunotherapy Against Inflammatory Osteolysis

10.21203/rs.3.rs-885656/v1 ◽

2021 ◽

Author(s):

Cheng Ding ◽

Chuang Yang ◽

Tao Cheng ◽

Xingyan Wang ◽

Qiaojie Wang ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Inflammatory Responses ◽

Total Joint Replacement ◽

Major Complication ◽

Dual Model ◽

Joint Replacement Surgery ◽

Pro Inflammatory Cytokines ◽

Macrophage Membrane

Abstract Background：Inflammatory osteolysis is a major complication of total joint replacement surgery that can cause prosthesis failure and necessitate revision surgery. Macrophages are key effector immune cells in inflammatory responses, but excessive M1-polarization of dysfunctional macrophages leads to the secretion of pro-inflammatory cytokines and severe loss of bone tissue. Here, we report the development of macrophage-biomimetic porous SiO2-coated ultrasmall Se particles (Porous Se@SiO2 nanospheres) for the management of inflammatory osteolysis. Results: Macrophage-membrane-coated porous Se@SiO2 nanospheres(M-Se@SiO2) can attenuate lipopolysaccharide (LPS)-induced inflammatory osteolysis by a dual-immunomodulatory effect. As macrophage membrane decoys, these nanoparticles reduce toxin levels and neutralize pro-inflammatory cytokines. Moreover, the release of Se can induce the polarization of macrophages toward the anti-inflammatory M2-phenotype. These effects are mediated via the inhibition of p65, p38, and extracellular signal-regulated kinase(ERK) signaling. Additionally, the immune environment created by M-Se@SiO2 reduces the inhibition of osteogenic differentiation caused by pro-inflammation cytokines, confirmed through in vitro and in vivo experiments.Conclusion: Our findings suggest that M-Se@SiO2 has an immunomodulatory role in LPS-induced inflammation and bone remodeling, which demonstrates that M-Se@SiO2 is a promising engineered nano-platform for the treatment of osteolysis arising after arthroplasty.

Download Full-text