scholarly journals IRAK-4 in macrophages contributes to inflammatory osteolysis of wear particles around loosened hip implants

2021 ◽  
pp. 175342592110187
Author(s):  
Yang-chun Zhang ◽  
Jian-hong Xiao ◽  
Shao-jie Deng ◽  
Guo-liang Yi
Keyword(s):  
Endotoxin Tolerance ◽  
Wear Particles ◽  
Hip Implants ◽  
Prosthesis Loosening ◽  
Specific Mechanism ◽  
Local Immunity ◽  
Tnf Α ◽  
Local Inflammatory Reaction ◽  
Pro Inflammatory Cytokines

TLRs recognizing PAMPS play a role in local immunity and participate in implant-associated loosening. TLR-mediated signaling is primarily regulated by IL-1 receptor associated kinase-M (IRAK-M) negatively and IRAK-4 positively. Our previous studies have proved that wear particles promote endotoxin tolerance in macrophages by inducing IRAK-M. However, whether IRAK-4 is involved in inflammatory osteolysis of wear particles basically, and the specific mechanism of IRAK-4 around loosened hip implants, is still unclear. IRAK-4 was studied in the interface membranes from patients in vivo and in particle-stimulated macrophages to clarify its role. Also, IL-1β and TNF-α levels were measured after particle and LPS stimulation in macrophages with or without IRAK-4 silenced by siRNA. Our results showed that the interface membranes around aseptic and septic loosened prosthesis expressed more IRAK-4 compared with membranes from osteoarthritic patients. IRAK-4 in macrophages increased upon particle and LPS stimulation. In the former, IL-1β and TNF-α levels were lower compared with those of LPS stimulation, and IRAK-4 siRNA could suppress production of pro-inflammatory cytokines. These findings suggest that besides IRAK-M, IRAK-4 also plays an important role in the local inflammatory reaction and contributes to prosthesis loosening.

scholarly journals Dipterocarpus tuberculatus Roxb. Ethanol Extract Has Anti-Inflammatory and Hepatoprotective Effects In Vitro and In Vivo by Targeting the IRAK1/AP-1 Pathway

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2529
Author(s):  
Haeyeop Kim ◽  
Woo Seok Yang ◽  
Khin Myo Htwe ◽  
Mi-Nam Lee ◽  
Young-Dong Kim ◽  
...  
Keyword(s):  
Ethanol Extract ◽  
Serum Levels ◽  
Hepatoprotective Activity ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Related Proteins ◽  
Pro Inflammatory Cytokines ◽  
Inflammatory Effect

Dipterocarpus tuberculatus Roxb. has been used traditionally as a remedy for many diseases, especially inflammation. Therefore, we analyzed and explored the mechanism of the anti-inflammatory effect of a Dipterocarpus tuberculatus Roxb. ethanol extract (Dt-EE). Dt-EE clearly and dose-dependently inhibited the expression of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β in lipopolysaccharide (LPS)-treated RAW264.7 cells. Also, Dt-EE suppressed the activation of the MyD88/TRIF-mediated AP-1 pathway and the AP-1 pathway related proteins JNK2, MKK4/7, and TAK1, which occurred as a result of inhibiting the kinase activity of IRAK1 and IRAK4, the most upstream factors of the AP-1 pathway. Finally, Dt-EE displayed hepatoprotective activity in a mouse model of hepatitis induced with LPS/D-galactosamine (D-GalN) through decreasing the serum levels of alanine aminotransferase and suppressing the activation of JNK and IRAK1. Therefore, our results strongly suggest that Dt-EE could be a candidate anti-inflammatory herbal medicine with IRAK1/AP-1 inhibitory and hepatoprotective properties.

scholarly journals Steroid Sulfates from Ophiuroids (Brittle Stars): Action on Some Factors of Innate and Adaptive Immunity

2016 ◽  
Vol 11 (6) ◽  
pp. 1934578X1601100
Author(s):  
Anna K Gazha ◽  
Lyudmila A. Ivanushko ◽  
Eleonora V. Levina ◽  
Sergey N. Fedorov ◽  
Tatyana S. Zaporozets ◽  
...  
Keyword(s):  
Adaptive Immunity ◽  
Inflammatory Cytokines ◽  
Brittle Stars ◽  
Innate And Adaptive Immunity ◽  
Functional Activities ◽  
In Vivo Experiments ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

The action of seven polyhydroxylated sterol mono- and disulfates (1-7), isolated from ophiuroids, on innate and adaptive immunity was examined in in vitro and in vivo experiments. At least, three of them (1, 2 and 4) increased the functional activities of neutrophils, including levels of oxygen-dependent metabolism, adhesive and phagocytic properties, and induced the expression of pro-inflammatory cytokines TNF-α and IL-8. Compound 4 was the most active for enhancing the production of antibody forming cells in the mouse spleen.

scholarly journals IKK-2 inhibitor TPCA-1 represses nasal epithelial inflammation in vitro

2011 ◽  
Vol 49 (2) ◽  
pp. 168-173
Author(s):  
F. Sachse ◽  
K. Becker ◽  
T.J. Basel ◽  
D. Weiss ◽  
C. Rudack
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Disease ◽  
Inflammatory Process ◽  
Nasal Polyposis ◽  
Paraffin Sections ◽  
Tnf Α ◽  
Epithelial Inflammation ◽  
Pro Inflammatory Cytokines

BACKGROUND: Nasal polyposis (NP) is considered a subgroup within chronic rhinosinusitis. NP can be further subdivided into aspirin sensitive- and aspirin tolerant types (ASNP/ ATNP). Although the true etiology of NP has not been identified so far, it is agreed that NP represents an inflammatory disease of the nasal mucosa. Alterations of cellular kinase activities including that of IKK-2 might play a role in this inflammatory process. METHODS: Paraffin sections of ASNP, ATNP and controls were immunostained with Phospho-IkB-α antibody that detects the direct IKK-2 product (IkB-α. Intensity of epithelial staining was analysed semi-quantitatively by two independent observers. In cultured nasal polyp epithelial cells (NPECs) epithelial derived cytokines IL-8 and GRO α were induced by TNF-α or Staphylococcal supernatants and subsequently repressed by IKK-2 inhibitor TPCA-1. RESULTS: Significant Phospho-IkB-α staining was observed in the nasal epithelium of ASNP compared to ATNP and controls suggesting strong IKK-2 activation in patients with ASNP in vivo. In vitro, pro-inflammatory cytokines IL-8 and GRO-α in NPECs were significantly repressed by TPCA-1. CONCLUSION: IKK-2 activity is increased in the subgroup of ASNP. IL-8 and GRO-α responses were repressed by IKK-2 inhibitor TPCA-1 in vitro. IKK-2 inhibitors might represent a potential target for anti-inflammatory intervention in ASNP.

Over-expression of PTEN attenuates the inflammation of fibroblast-like synoviocytes in rheumatoid arthritis

2020 ◽  
Author(s):  
Xiao-Feng Li ◽  
Qing-Qing Xu ◽  
Man-Wen Yang ◽  
He Chen ◽  
Su-Qin Yin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Dna Methylation ◽  
Inflammatory Cytokines ◽  
Pten Expression ◽  
Over Expression ◽  
Tnf Α ◽  
And Migration ◽  
Fibroblast Like Synoviocytes ◽  
Pro Inflammatory Cytokines

Abstract Background: Rheumatoid arthritis (RA) is characterized by a tumor-like expansion of the synovium and the subsequent destruction of adjacent articular cartilage and bone. Recent studies have shown that phosphatase and tension homolog deleted on chromosome 10 (PTEN) might contribute to the survival of fibroblast-like synoviocytes (FLS) and the production of pro-inflammatory cytokines in RA.Methods : The expression was determined in RA and adjuvant-induced arthritis (AIA) synovial tissues by immunohistochemistry. FLSs were treatment with bpv, PTEN-RNAi or over-expression plasmid in RA and AIA. FLSs migration was assessed. The ad-PTEN was also injected into the knee of AIA in vivo. Chromatin Immunoprecipitation (ChIP) and Methylation-special PCR (MSP) assay were used to study the expression of PTEN mRNA in DNA methylation.Results : Down-regulated level of PTEN expression was observed in RA and AIA. Inhibition PTEN expression by bpv or PTEN-RNAi could promote the expression of pro-inflammatory cytokines, chemokines and migration of FLS with TNF-α in RA and AIA. Consistently, over-expression of PTEN reduced their low-expression of pro-inflammatory cytokines, chemokines and migration. Intra-articular injection of ad-PTEN in AIA knees dramatically reduced inflammatory and paw swelling in vivo. The ChIP and MSP assay has clearly detected the DNA methylation of PTEN was increased in FLS with TNF-α. Moreover, intraperitoneally injected 5-Aza in AIA also suppressed the inflammatory and paws swelling in vivo.Conclusions: Our findings suggest that over-expression PTEN attenuates the formation of pro-inflammatory cytokines, chemokines and migration of FLS, and it may be regulated by DNA methylation in the pathogenesis of RA.

scholarly journals Lyophilized Symbiotic Mitigates Mucositis Induced by 5-Fluorouracil

2021 ◽  
Vol 12 ◽  
Author(s):  
Bruna Savassi ◽  
Bárbara F. Cordeiro ◽  
Sara H. Silva ◽  
Emiliano R. Oliveira ◽  
Giovanna Belo ◽  
...  
Keyword(s):  
Weight Loss ◽  
Adjuvant Treatment ◽  
Protein Isolate ◽  
Mucosal Inflammation ◽  
Lyophilized Formulation ◽  
Reduce Weight Loss ◽  
Tnf Α ◽  
Probiotic Strains ◽  
Pro Inflammatory Cytokines

Mucositis is an adverse effect of cancer chemotherapies using 5-Fluorouracil (5-FU). It is characterized by mucosal inflammation, pain, diarrhea, and weight loss. Some studies reported promising healing effects of probiotic strains, when associated with prebiotics, as adjuvant treatment of mucositis. We developed a lyophilized symbiotic product, containing skimmed milk, supplemented with whey protein isolate (WPI) and with fructooligosaccharides (FOS), and fermented by Lactobacillus casei BL23, Lactiplantibacillus plantarum B7, and Lacticaseibacillus rhamnosus B1. In a mice 5-FU mucositis model, this symbiotic lyophilized formulation was able to reduce weight loss and intestinal permeability. This last was determined in vivo by quantifying blood radioactivity after oral administration of 99mTc-DTPA. Finally, histological damages caused by 5-FU-induced mucositis were monitored. Consumption of the symbiotic formulation caused a reduced score of inflammation in the duodenum, ileum, and colon. In addition, it decreased levels of pro-inflammatory cytokines IL-1β, IL-6, IL-17, and TNF-α in the mice ileum. The symbiotic product developed in this work thus represents a promising adjuvant treatment of mucositis.

scholarly journals Bone Resorption Induced by Titanium Implantation Through Activation of Osteoclast Formation via C3a

2020 ◽  
Author(s):  
Xiaohan Liu ◽  
Siwen Li ◽  
Yuan Meng ◽  
Yu Fan ◽  
Ce Shi ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Inflammatory Responses ◽  
Titanium Implant ◽  
Osteoclast Formation ◽  
Alternative Pathways ◽  
Tnf Α ◽  
Differentiation And Proliferation ◽  
Pro Inflammatory Cytokines

Abstract Titanium implantation is widely used for dental replacement with advantages of excellent mechanical strength, corrosion resistance, chemical stability and biocompatibility. Some patients, however, are subject to the failure of implantation due to bone resorption, which closely related to the inflammatory responses without clear mechanisms. In this study, first we found that there were inflammatory responses and increases of osteoclasts in the surrounding tissues near by the titanium implant. Further, data revealed that the C3 was increased in the serum and surrounding tissues near by the titanium implant, and activated by classical and alternative pathways. Next, we recognized that the C3a/C3aR, no C3b played an important role in stimulating secretions of pro-inflammatory cytokines of TNF-α and MMP9 via transcription factors NF-kB and NFATc1. This cascade of responses to titanium implant leaded the differentiation and proliferation of osteoclasts in vivo and in vitro, bone resorption of surrounding tissues of Ti implant. These suggest that the cleaved C3a fragment plays predominant roles in the activation of osteoclast. Therefore, the blocking C3a activation should provide potential to prevent bone resorption and prolong the survival of biomaterial implants.

scholarly journals Lactobacillus ruminis Alleviates DSS-Induced Colitis by Inflammatory Cytokines and Gut Microbiota Modulation

Foods ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1349
Author(s):  
Bo Yang ◽  
Mingjie Li ◽  
Shuo Wang ◽  
R. Paul Ross ◽  
Catherine Stanton ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Inflammatory Cytokines ◽  
Short Chain Fatty Acids ◽  
Colon Tissue ◽  
Tnf Α ◽  
Lactobacillus Ruminis ◽  
Immune Response In Vitro ◽  
Pro Inflammatory Cytokines

Lactobacillus ruminis can stimulate the immune response in vitro, but previous studies were only carried out in vitro and the anti-inflammatory effects of L. ruminis needs more in vivo evidences. In this study, the immune regulation and potential mechanisms of L. ruminis was investigated in DSS-induced colitis mice. L. ruminis FXJWS27L3 and L. ruminis FXJSW17L1 relieved the symptoms of colitis, including inhibition of colon shortening and colon tissue damage. L. ruminis FXJWS27L3 significantly reduced the pro-inflammatory cytokines IL-1β, TNF-α, and IL-17, while L. ruminis FXJSW17L1 significantly increased short chain fatty acids in mice feces. Moreover, L. ruminis FXJWS27L3 and L. ruminis FXJSW17L1 treatments significantly increased the gut microbiota diversity and balance the intestine microbiota profiles, which improved the imbalance of intestine microbiota composition to a certain extent. The results showed that L. ruminis can alleviate DSS-induced colitis, which possibly was related to promoting the expression of pro-inflammatory cytokines, up-regulating SCFAs and restoring the imbalance of gut microbiota.

scholarly journals Rutin Ameliorates Malaria Pathogenesis by Modulating Inflammatory Mechanism: An In-Vitro and In-Vivo Study

2021 ◽  
Author(s):  
Divya Bhatt ◽  
Saurabh Kumar ◽  
Parmanand Kumar ◽  
Surbhi Bisht ◽  
Anil Kumar Maurya ◽  
...  
Keyword(s):  
Food Supplement ◽  
Flavonoid Glycoside ◽  
Macrophage Cells ◽  
Inflammatory Mechanism ◽  
Tnf Α ◽  
Resistant Strains ◽  
The Mean ◽  
Pro Inflammatory Cytokines

Abstract Rutin (3,3’,4’ 5,7-pentahydroxyflavone-3-rhamnoglucoside) is a flavonoid glycoside, found in many edible plants such as buckwheat and berries. Rutin as a food supplement is recommended for the treatment of various diseases, which directed us to investigate its valuable effects in malaria induced pathogenesis. In the present study, Rutin was tested for its anti-plasmodial activity against chloroquine sensitive and resistant strains (NF-54 and K1) of Plasmodium falciparum and studied for its anti-oxidative and anti-inflammatory potential against LPS stimulated macrophage cells. In vitro observations were further validated using an in-vivo physiological rodent model of Plasmodium berghei-induced malaria pathogenesis. Rutin was also tested for its effect in combination with chloroquine.Rutin was found to have potent anti-plasmodial activity against both chloroquine sensitive and resistant strains of P. falciparum (NF-54 and K1). It was able to reduce the oxidative stress induced by LPS in macrophage cells with decreased production of pro-inflammatory cytokines (IL-6, TNF-α and IL-1β). Rutin was found to significantly suppress the parasitaemia, increase the mean survival time and restored the haemoglobin and glucose level in in vivo assays. This was corroborated by reduced production of malondialdehyde (MDA) and pro-inflammatory mediators in rutin treated mice in P.berghei-induced malaria pathogenesis. Interestingly, the combination of rutin with chloroquine had shown synergy in both in vitro and in vivo experiments. The findings of the present study thus highlighted the suitability of rutin for further study in the management of drug resistant malaria, alone or in combination with other compounds.

scholarly journals Anti-inflammatory activity of methanolic extract of Ficus hispida dried fruit

2021 ◽  
Vol 10 (8) ◽  
pp. 997
Author(s):  
Asif Choudhury ◽  
Deepak Kumar Jha ◽  
U. Rajashekhar
Keyword(s):  
Inflammatory Cytokines ◽  
Methanolic Extract ◽  
Inflammatory Activity ◽  
Bioactive Metabolites ◽  
Paw Oedema ◽  
Tnf Α ◽  
Ficus Hispida ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Background: Natural products are a valuable resource of novel bioactive metabolites and these products exist in which the anti-inflammatory activity. The present investigation studies the in vivo and in vitro anti-inflammatory activity of methanolic extract of Ficus hispida in rat’s model.Methods: Plant material was extracted with methanol in a Soxhlet extraction apparatus. Indomethacin was used as a standard drug here, which is a known potent inhibitor of PG synthesis. The carrageenin and histamine induced paw oedema were selected to represent models of acute inflammations. The test compounds and standard drugs were administered orally. After 60 minutes paw oedema was induced by giving 0.1 ml of 1% Carrageenan and 0.1 % histamine by sub-plantar administration. Paw volume-Plethysmometer by mercury displacement method, before and after 1 hr to 4 hours of carrageenan and histamine administration. Performed MTT-based cytotoxicity assay of the Ficus hispida on the RAW264.7 cell line to determine the IC50 and calculate the pro-inflammatory cytokines viz, IL-6, IL-1β and TNF-α and compared to the LPS control.Results: The result obtained from the in-vivo study shows that the Ficus hispida has significant anti- inflammatory activity in a dose dependent manner. This effect is similar to that produced by NSAIDS such as Indomethacin. The concentrations of IL-6, IL-1β and TNF-α, secreted by the cells after challenging with bacterial LPS (2 µg/ml) and subsequent treatment with 50 µg Ficus hispida has been found to reduce the production of all the three pro-inflammatory cytokines viz, IL-6, IL-1β and TNF-α as compared to the LPS control. The activity, in fact, is comparable to the standard NSAID Indomethacin.Conclusions: All these findings and phytoconstituents present in the extract could be the possible chemicals involved in the prevention of inflammations.

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