Related Experiment Video
Updated: Jun 26, 2026
06:29
Accurate and Simple Measurement of the Pro-inflammatory Cytokine IL-1β using a Whole Blood Stimulation Assay
Published on: March 1, 2011
Meprin A and meprin alpha generate biologically functional IL-1beta from pro-IL-1beta
Christian Herzog1, Randy S Haun, Varsha Kaushal
1Central Arkansas Veterans Healthcare System, 4300 W. 7th Street, 111D, Little Rock, AR 72205, USA.
Biochemical and Biophysical Research Communications
|January 13, 2009
Summary
Meprin A and meprin alpha generate active interleukin-1beta (IL-1beta) by cleaving its precursor. This process is crucial for inflammation and tissue injury, as shown in a sepsis model.
Area of Science:
- Biochemistry
- Immunology
- Molecular Biology
Background:
- Interleukin-1beta (IL-1beta) is a key inflammatory cytokine.
- Its precursor, pro-IL-1beta, requires specific cleavage for biological activity.
- Meprin metalloendopeptidases are implicated in various biological processes.
Purpose of the Study:
- To investigate the role of meprin A and meprin alpha in pro-IL-1beta processing.
- To compare the biological activity of IL-1beta generated by meprins versus other proteases.
- To assess the in vivo relevance of meprin-mediated IL-1beta production in a sepsis model.
Main Methods:
- Purification of meprin A and expression of recombinant meprin alpha.
- Amino-acid sequencing to identify cleavage sites on pro-IL-1beta.
- Assay of IL-1beta biological activity using helper T-cell proliferation.
- Induction of sepsis in mice via cecal ligation puncture and administration of meprin inhibitor actinonin.
Main Results:
- Meprin A and meprin alpha cleave pro-IL-1beta at the His(115)-Asp(116) bond, generating active IL-1beta.
- IL-1beta produced by meprin A exhibited 3-fold higher biological activity than that from meprin beta or caspase-1.
- In a mouse sepsis model, the meprin inhibitor actinonin significantly reduced serum IL-1beta levels.
Conclusions:
- Meprin A and meprin alpha are potent producers of biologically active IL-1beta.
- These enzymes cleave pro-IL-1beta at a site distinct from, but near, the caspase-1 site.
- Meprin A and meprin alpha play a significant role in IL-1beta production during inflammation and tissue injury.
Related Concept Videos
01:11IP3/DAG Signaling Pathway
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
01:30Production of Pharmaceuticals
Industrial insulin production uses genetically engineered E. coli expressing a proinsulin gene controlled by a tryptophan promoter and containing a methionine linker for later cleavage. The cells also carry ampicillin resistance for selective growth. Seed cultures are stored at −80 °C and production begins by thawing a small amount to inoculate starter cultures, which are progressively scaled to a 50,000-L bioreactor. In the bioreactor, E. coli grow in nutrient-rich media under sterile, tightly...
01:31Regulation of the Unfolded Protein Response
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
01:23Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
Prostacyclin receptor agonists are a class of therapeutic agents integral to managing pulmonary arterial hypertension (PAH). These drugs operate by mimicking the action of prostaglandin I2, or PGI2, a naturally occurring compound in the body.
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...