Meprin A and meprin α generate biologically functional IL-1β from pro-IL-1β
| Autor: | Gur P. Kaushal, Varsha Kaushal, Sudhir V. Shah, Randy S. Haun, Philip R. Mayeux, Christian Herzog |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Kidney Cortex
Interleukin-1beta Molecular Sequence Data Biophysics Caspase 1 Biology Hydroxamic Acids Biochemistry Article law.invention Mice chemistry.chemical_compound law Sepsis Animals Amino Acid Sequence Protein Precursors Actinonin Molecular Biology Peptide sequence chemistry.chemical_classification Meprin A Metalloendopeptidases Biological activity T-Lymphocytes Helper-Inducer Cell Biology Molecular biology Recombinant Proteins Rats Amino acid Disease Models Animal chemistry Recombinant DNA Metalloendopeptidase Interleukin-1 |
| Zdroj: | Biochemical and Biophysical Research Communications. 379:904-908 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2008.12.161 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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