Linked Life Data

9759850

Source:http://linkedlifedata.com/resource/pubmed/id/9759850

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1998-10-22
pubmed:abstractText
Biologic activity of IL-1 beta requires processing of the inactive precursor, a function generally ascribed to IL-1 beta-converting enzyme (caspase-1). However, alternative mechanisms of IL-1 beta activation have been postulated in local inflammatory reactions. Expression of IL-1 beta and matrix metalloproteinases (MMPs) frequently occurs simultaneously at sites of inflammation. We describe here that stromelysin-1 (MMP-3), as well as the gelatinases A (MMP-2) and B (MMP-9), processes recombinant human IL-1 beta precursor (pIL-1 beta) into biologically active forms. Detection of both pIL-1 beta processing and biologic IL-1 beta activity demonstrated different processing capacities of the respective MMPs. Conversion of pIL-1 beta by stromelysin-1 required coincubation for at least 1 h, and biologic activity faded after 8 h to 24 h. Gelatinase A was less effective in processing pIL-1 beta, requiring at least 24 h of coincubation. In contrast, gelatinase B processed pIL-1 beta within minutes, resulting in immunoreactive products as well as biologic activity stable for 72 h. In addition, prolonged incubation of mature IL-1 beta with stromelysin-1, and to a lesser extent also with gelatinases, but not with interstitial collagenase, resulted in the degradation of mature IL-1 beta. None of the MMPs processed the second isoform of IL-1, IL-1 alpha. The present study indicates a biphasic regulation of IL-1 beta activity by MMPs: a caspase-1-independent pathway of IL-1 beta activation and inhibition of IL-1 beta activity by degrading the mature cytokine. The balance of the respective MMPs and pIL-1 beta might regulate the long term appearance of IL-1 beta activity at sites of acute or chronic inflammation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
161
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3340-6
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:9759850-Animals, pubmed-meshheading:9759850-Caspase 1, pubmed-meshheading:9759850-Cell Line, pubmed-meshheading:9759850-Collagenases, pubmed-meshheading:9759850-Cysteine Endopeptidases, pubmed-meshheading:9759850-Dose-Response Relationship, Immunologic, pubmed-meshheading:9759850-Extracellular Space, pubmed-meshheading:9759850-Gelatinases, pubmed-meshheading:9759850-Humans, pubmed-meshheading:9759850-Interleukin-1, pubmed-meshheading:9759850-Matrix Metalloproteinase 2, pubmed-meshheading:9759850-Matrix Metalloproteinase 3, pubmed-meshheading:9759850-Matrix Metalloproteinase 9, pubmed-meshheading:9759850-Metalloendopeptidases, pubmed-meshheading:9759850-Mice, pubmed-meshheading:9759850-Molecular Weight, pubmed-meshheading:9759850-Protein Precursors, pubmed-meshheading:9759850-Protein Processing, Post-Translational, pubmed-meshheading:9759850-Recombinant Proteins, pubmed-meshheading:9759850-T-Lymphocytes, pubmed-meshheading:9759850-Time Factors
pubmed:year
1998
pubmed:articleTitle
Generation of biologically active IL-1 beta by matrix metalloproteinases: a novel caspase-1-independent pathway of IL-1 beta processing.
pubmed:affiliation
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't