Several endogenous peptides, including bradykinin and substance P, have potent inflammatory effects in the joint. Levels of these peptides are regulated by plasma and cell-associated peptide degrading enzymes. One of these peptidases, neutral endopeptidase-24.11 (NEP-24.11), is expressed constitutively and in high density on human synovial cells and is presumed to play a critical role in local regulation of peptide levels in the joint. We examined the role of endogenous NEP-24.11 in regulating bradykinin-mediated effects in an articular model, and investigated the ability of soluble, recombinant human NEP-24.11 to augment the effects of the endogenous enzyme. Our studies demonstrate that endogenous synovial NEP-24.11 does not significantly modulate inflammatory peptide effects on cells when competing with colocalizing peptide receptors expressed in high density. Administration of excess, soluble recombinant NEP-24.11 can overcome this problem, however. Furthermore, the activity of the recombinant enzyme was not compromised in the presence of oxidants or inflammatory joint fluids. Recombinant NEP-24.11 holds promise as a novel therapeutic strategy for the treatment of inflammatory arthritis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1023/a:1022304025789 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Expression and purification of recombinant proteins in is a bedrock technique in biochemistry and molecular biology. Expression optimization requires testing different combinations of solubility tags, affinity purification techniques, and site-specific proteases. This optimization is laborious and time consuming as these features are spread across different vector series and require different cloning strategies with varying efficiencies.
View Article and Find Full Text PDFGeneration and characterization of OX40-ligand fusion protein that agonizes OX40 on T-Lymphocytes.
Front Immunol
January 2025
Laboratory of Molecular Cell Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
OX40, a member of the tumor necrosis factor (TNF) receptor superfamily, is expressed on the surface of activated T cells. Upon interaction with its cognate ligand, OX40L, OX40 transmits costimulatory signals to antigen-primed T cells, promoting their activation, differentiation, and survivalprocesses essential for the establishment of adaptive immunity. Although the OX40-OX40L interaction has been extensively studied in the context of disease treatment, developing a substitute for the naturally expressed membrane-bound OX40L, particularly a multimerized OX40L trimers, that effectively regulates OX40-driven T cell responses remains a significant challenge.
View Article and Find Full Text PDFBacterial expression, purification and characterization of the human Dectin-1 lectin domain for structural and functional studies.
Protein Expr Purif
January 2025
Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Miyagi 981-8558, Japan. Electronic address:
Dectin-1 (CLEC7A), a C-type lectin-like receptor that recognizes β-1,3 glucans, has a key role in the innate immune system. While the lectin domain of mouse Dectin-1 has been solubilized and refolded from inclusion bodies in Escherichia coli, similar refolding of the human Dectin-1 lectin domain is hindered by the formation of misfolded multimers with aberrant intermolecular disulfide bonds. The aim of this study was to develop a method for the large-scale production of the human Dectin-1 lectin domain.
View Article and Find Full Text PDFChloramphenicol glycoside derivative: A way to overcome its antimicrobial resistance and toxicity.
Carbohydr Res
January 2025
Faculty of Chemistry, University of Wrocław, Wrocław, 50-383, Poland.
Triggered by the urgent need to tackle the global crisis of multidrug-resistant bacterial infections, in this work, we present a way to overcome chloramphenicol resistance by introducing modifications based on the glycosylation of its hydroxyl groups. The synthesized derivatives demonstrate complete resistance to the action of recombinant chloramphenicol acetyltransferase (CAT) from Escherichia coli and efficacy against methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli ESBL, and Pseudomonas aeruginosa ATCC 27853. Glycosylation gives chloramphenicol an additional advantage - the stable glycosidic form is less toxic to human dermal fibroblasts and has significantly better water solubility than non-glycosylated chloramphenicol.
View Article and Find Full Text PDFOptimization of Conditions for Production of Soluble Poly(A)-Polymerase for Biotechnological Applications.
Biology (Basel)
January 2025
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences (ICBFM SB RAS), 8, Lavrentiev Avenue, Novosibirsk 630090, Russia.
Poly(A) polymerase (PAP 1) from is the primary enzyme responsible for synthesizing poly(A) tails on RNA molecules, signaling RNA degradation in bacterial cells. In vitro, PAP 1 is used to prepare libraries for RNAseq and to produce mRNA vaccines. However, PAP 1's toxicity and instability in low-salt buffers complicate its expression and purification.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!