Meprin A and meprin alpha generate biologically functional IL-1beta from pro-IL-1beta.

Abstract

The present study demonstrates that both oligomeric metalloendopeptidase meprin A purified from kidney cortex and recombinant meprin alpha are capable of generating biologically active IL-1beta from its precursor pro-IL-1beta. Amino-acid sequencing analysis reveals that meprin A and meprin alpha cleave pro-IL-1beta at the His(115)-Asp(116) bond, which is one amino acid N-terminal to the caspase-1 cleavage site and five amino acids C-terminal to the meprin beta site. The biological activity of the pro-IL-1beta cleaved product produced by meprin A, determined by proliferative response of helper T-cells, was 3-fold higher to that of the IL-1beta product produced by meprin beta or caspase-1. In a mouse model of sepsis induced by cecal ligation puncture that results in elevated levels of serum IL-1beta, meprin inhibitor actinonin significantly reduces levels of serum IL-1beta. Meprin A and meprin alpha may therefore play a critical role in the production of active IL-1beta during inflammation and tissue injury.

• Authors: Christian Herzog, Randy S Haun, Varsha Kaushal, Philip R Mayeux, Sudhir V Shah, Gur P Kaushal
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 379 Issue 4 Pg. 904-8 (Feb 20 2009) ISSN: 1090-2104 [Electronic] United States
• PMID: 19135030 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Hydroxamic Acids
• Interleukin-1
• Interleukin-1beta
• Protein Precursors
• Recombinant Proteins
• interleukin 1 precursor
• Metalloendopeptidases
• meprin A
• actinonin

Topics

• Amino Acid Sequence
• Animals
• Disease Models, Animal
• Hydroxamic Acids (pharmacology)
• Interleukin-1 (metabolism)
• Interleukin-1beta (antagonists & inhibitors, biosynthesis, pharmacology)
• Kidney Cortex (enzymology)
• Metalloendopeptidases (antagonists & inhibitors, genetics, isolation & purification, metabolism)
• Mice
• Molecular Sequence Data
• Protein Precursors (metabolism)
• Rats
• Recombinant Proteins (antagonists & inhibitors, genetics, metabolism)
• Sepsis (enzymology, immunology)
• T-Lymphocytes, Helper-Inducer (drug effects, immunology)