Construction of an Anti-IL-1β scfv and TNFRI Fusion Protein and Its Therapeutic Effect on RA Mice Model

2014 ◽  
Vol 14 (12) ◽  
pp. 1048-1061 ◽  
Author(s):  
Fangming Kan ◽  
Guiping Ren ◽  
Mo Guo ◽  
Jianying Qi ◽  
Yu Zhang ◽  
...  
2011 ◽  
Vol 44 (13) ◽  
pp. S46
Author(s):  
Elham Mohit ◽  
Azam Bolhassani ◽  
Farnaz Zahedifard ◽  
Mohammad Taghikhani ◽  
Eslamifar Ali ◽  
...  

2013 ◽  
Vol 58 (4) ◽  
Author(s):  
Gandhirajan Anugraha ◽  
Parasurama Jeyaprita ◽  
Jayaprakasam Madhumathi ◽  
Tamilvanan Sheeba ◽  
Perumal Kaliraj

AbstractAlthough multiple vaccine strategy for lymphatic filariasis has provided tremendous hope, the choice of antigens used in combination has determined its success in the previous studies. Multiple antigens comprising key vaccine candidates from different life cycle stages would provide a promising strategy if the antigenic combination is chosen by careful screening. In order to analyze one such combination, we have used a chimeric construct carrying the well studied B. malayi antigens thioredoxin (BmTRX) and venom allergen homologue (BmVAH) as a fusion protein (TV) and evaluated its immune responses in mice model. The efficacy of fusion protein vaccine was explored in comparison with the single antigen vaccines and their cocktail. In mice, TV induced significantly high antibody titer of 1,28,000 compared to cocktail vaccine TRX+VAH (50,000) and single antigen vaccine TRX (16,000) or VAH (50,000). Furthermore, TV elicited higher level of cellular proliferative response together with elevated levels of IFN-γ, IL-4 and IL-5 indicating a Th1/Th2 balanced response. The isotype antibody profile showed significantly high level of IgG1 and IgG2b confirming the balanced response elicited by TV. Immunization with TV antigen induced high levels of both humoral and cellular immune responses compared to either cocktail or antigen given alone. The result suggests that TV is highly immunogenic in mice and hence the combination needs to be evaluated for its prophylactic potential.


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S155-S155
Author(s):  
R Golan-Gerstl ◽  
N Koroukhov ◽  
Y Elbaum Shiff ◽  
I Shilo ◽  
S Reif

Abstract Background Inflammatory bowel disease (IBD) is a complex disorder that results from a dysregulated immune response in the gut. Emerging therapy for IBD treatment is mainly focused on regulation of the immune response. Exosomes are nanovesicle packing different molecules such as miRNAs that transfer their cargo to recipient cells. We and others found that mammalian milk contain high concentration of exosomes (milk-derived exosomes, MDE) carrying beneficial miRNAs such as miRNA-148. Furthermore, MDE are taken up by different cell type such as intestinal epithelial cells, modify target gene expression, promote proliferation and differentiation of colon epithelial cells. The aim of this study is to explore the therapeutic effect of MDE on colitis. Methods We used gavage administration of MDE labelled with DiR dye to track their localisation patterns in vivo. The therapeutic effect of MDE on colitis was study in mice model of SDS induced colitis, colon length, histopathological scoring grade, cytokine expression, stool consistency and miRNA expression were analysed. Results Imaging of mouse that have receive labelled MDE revealed an accumulation of fluorescent signal in the intestine. Moreover, fluorescent signal in the intestine and liver is time dependent. MDE reduced the histopathological scoring grade from 5.83 ± 1.47 to 0.6 ± 0.6, p < 0.05. The length of the colon of MDE-treated animals was 7.9 ± 0.19 in comparison to 6.92 ± 0.3 p < 0.05 of the untreated. The weight loss as a result of the colitis was reverted in MDE-treated mice. Likewise, MDE treatment reduced IL-6, TNF-α and caveolin expression from 3.83 to 0.78, 1.59 to 0.86 and 3.52 to 1.1, respectively. Highly expressed miRNAs (miRNA-320, 375, Let-7a and 6073) were found to be more abundant in colon of MDE treatment mice compared with the untreated. Conclusion This study demonstrated that MDE have a therapeutic effect on colitis in vivo. Proving the effect of MDE on colitis will have implications for the potential of adding MDE as a therapeutic nutrient to be included in the formulas for IBD patients.


2019 ◽  
Vol 37 (2) ◽  
Author(s):  
Cristine Steen-Louws ◽  
Peter Boross ◽  
Judith Prado ◽  
Jan Meeldijk ◽  
Jurgen B. Langenhorst ◽  
...  

Abstract Purpose Modulating sialylation of therapeutic glycoproteins may be used to influence their clearance and systemic exposure. We studied the effect of low and high sialylated IL4–10 fusion protein (IL4–10 FP) on in vitro and in vivo bioactivity and evaluated the effect of differential sialylation on pharmacokinetic parameters. Methods CHO cell lines producing low (IL4–10 FP lowSA) and high sialylated (IL4–10 FP highSA) fusion protein were generated. Bioactivity of the proteins was evaluated in an LPS-stimulated whole blood assay. Pharmacokinetics were studied in rats, analyzing plasma levels of IL4–10 FP upon intravenous injection. In vivo activity was assessed in an inflammatory pain mice model upon intrathecal injection. Results IL4–10 FP lowSA and IL4–10 FP highSA had similar potency in vitro. The pharmacokinetics study showed a 4-fold higher initial systemic clearance of IL4–10 FP lowSA, whereas the calculated half-life of both IL4–10 FP lowSA and IL4–10 FP highSA was 20.7 min. Finally, both IL4–10 FP glycoforms inhibited persistent inflammatory pain in mice to the same extent. Conclusions Differential sialylation of IL4–10 fusion protein does not affect the in vitro and in vivo activity, but clearly results in a difference in systemic exposure. The rapid systemic clearance of low sialylated IL4–10 FP could be a favorable characteristic to minimize systemic exposure after administration in a local compartment.


Cytotherapy ◽  
2020 ◽  
Vol 22 (5) ◽  
pp. S49-S50 ◽  
Author(s):  
Y. Geffen ◽  
R. Horev ◽  
N. Perets ◽  
E. Marom ◽  
U. Danon ◽  
...  

2021 ◽  
Vol 21 (2) ◽  
pp. 1085-1090
Author(s):  
Chunxia Zhang ◽  
Qian Qin ◽  
Hongle Li

Steroids are the main drugs currently used to treat asthma. However, the toxic and side effects of these drugs and the tolerance of the drugs due to long-term administration are still problems in the clinical treatment of asthma. Bavachinin has a good effect in the treatment of mouse asthma models, and it can effectively inhibit the expression of a variety of cytokines. However, it is extremely difficult to dissolve in water, has low bioavailability, and is quickly cleared in the blood. These characteristics limit its clinical application potential. In this study, nanotechnology was used to construct an effective oral drug delivery system. Through analysis of serum-related antibodies and cytokines, the system showed significant therapeutic effects on asthma-positive groups. Far-infrared imaging results showed that the system has a good targeted enrichment effect on pathological parts, while showing lower toxicity and higher therapeutic effect. Whether it is the splenocyte flow typing or the analysis of lung tissue, the system has verified the excellent treatment, and through the observation of paraffin sections of lung tissue, it was found that the bronchial morphology returned to normal after drug treatment, and the leakage of inflammatory cells was significantly reduced.


2015 ◽  
Vol 309 (8) ◽  
pp. L872-L878 ◽  
Author(s):  
Ikuo Murakami ◽  
Ran Zhang ◽  
Masayuki Kubo ◽  
Kenjiro Nagaoka ◽  
Eri Eguchi ◽  
...  

Allergic asthma caused by continuous allergen exposure evokes allergen-specific Th2 responses and is characterized by chronic airway inflammation and hyperresponsiveness. A previous report showed that rebamipide improved asthmatic symptoms in an ovalbumin/trypsin mice model. However, it is still unclear how rebamipide exerts its effects in asthma. In this study, rebamipide improved the asthmatic responses induced by mite exposure in NC/Nga mice, revealing the mechanism of this therapeutic effect. Rebamipide suppressed the infiltration of eosinophils into the airways and lung as well as attenuating the production of reactive oxygen species in tissues. In addition to these anti-inflammatory effects, rebamipide inhibited the production of IL-33, a member of the IL-1 family that drives the subsequent production of Th2-associated cytokines. These observations identify the point where rebamipide exerts its suppressive action on asthma and suggest that rebamipide has therapeutic potential in preventing mite-induced asthma.


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