Carboxyterminal cleavage of the chemokines MIG and IP-10 by gelatinase B and neutrophil collagenase

Van den Steen, Philippe E.; Husson, Steven J.; Proost, Paul; Van Damme, Jo; Opdenakker, Ghislain

doi:10.1016/J.BBRC.2003.09.098

Title

Carboxyterminal cleavage of the chemokines MIG and IP-10 by gelatinase B and neutrophil collagenase

Author

Van den Steen, Philippe E.

Husson, Steven J.

Proost, Paul

Van Damme, Jo

Opdenakker, Ghislain

Abstract

Proteolytic processing is an important regulatory mechanism for chemokines. Matrix metalloproteinases (MMPs), such as gelatinase A/MMP-2 and gelatinase B/MMP-9, are known to process the aminoterminal end of various chemokines, including interleukin-8 (IL-8/CXCL-8) and monocyte chemotactic protein-3 (MCP-3/CXCL-7). In the present study, two proteases, gelatinase B and neutrophil collagenase/MMP-8, are shown for the first time to process the carboxyterminal end of two chemokines, monokine induced by interferon (IFN)-γ (MIG/CXCL-9) and IFN-inducible protein-10 (IP-10/CXCL-10). Neutrophil collagenase degrades MIG into small fragments and cleaves IP-10 behind positions 71 and 73. Gelatinase B degrades IP-10 and cleaves MIG at three different sites in its extended carboxyterminal region. This results in the formation of MIG(194), MIG(193), and MIG(190). In general, gelatinase B was more efficient than neutrophil collagenase in processing these chemokines. Alignment of the CXC chemokines with the respective cleavage sites by both MMPs identified the ELR motif as a possible determinant for amino terminal cleavage by these MMPs.

Language

English

Source (journal)

Biochemical and biophysical research communications. - New York, N.Y.

Publication

New York, N.Y. : 2003

ISSN

0006-291X

DOI

10.1016/J.BBRC.2003.09.098

Volume/pages

310 :3 (2003) , p. 889-896