MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily

Bootcov, MR, Bauskin, AR, Valenzuela, SM, Moore, AG, Bansal, M, He, XY, Zhang, HP, Donnellan, M, Mahler, S, Pryor, K, Walsh, BJ, Nicholson, RC, Fairlie, WD, Por, SB, Robbins, JM and Breit, SN (1997) MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily. Proceedings of the National Academy of Sciences of the United States of America, 94 21: 11514-11519. doi:10.1073/pnas.94.21.11514


Author Bootcov, MR
Bauskin, AR
Valenzuela, SM
Moore, AG
Bansal, M
He, XY
Zhang, HP
Donnellan, M
Mahler, S
Pryor, K
Walsh, BJ
Nicholson, RC
Fairlie, WD
Por, SB
Robbins, JM
Breit, SN
Title MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
ISSN 0027-8424
Publication date 1997-10-01
Year available 1997
Sub-type Article (original research)
DOI 10.1073/pnas.94.21.11514
Open Access Status Not Open Access
Volume 94
Issue 21
Start page 11514
End page 11519
Total pages 6
Place of publication WASHINGTON
Publisher NATL ACAD SCIENCES
Language eng
Abstract Macrophages play a key role in both normal and pathological processes involving immune and inflammatory responses, to a large extent through their capacity to secrete a wide range of biologically active molecules, To identify some of these as yet not characterized molecules, we have used a subtraction cloning approach designed to identify genes expressed in association with macrophage activation, One of these genes, designated macrophage inhibitory cytokine 1 (MIC-1), encodes a protein that bears the structural characteristics of a transforming growth factor beta (TGF-beta) superfamily cytokine, Although it belongs to this superfamily it has no strong homology to existing families, indicating that it is a divergent member that may represent the first of a new family within this grouping, Expression of MIC-1 mRNA in monocytoid cells is up-regulated by a variety of stimuli associated with activation, including interleukin 1 beta, tumor necrosis factor alpha (TNF-alpha), interleukin 2, and macrophage colony-stimulating factor but not interferon gamma, or lipopolysaccharide (LPS), Its expression is also increased by TGF-beta, Expression of MIC-1 in CHO cells results in the proteolytic cleavage of the propeptide and secretion of a cysteine-rich dimeric protein of M-r 25 kDa, Purified recombinant MIC-1 is able to inhibit lipopolysaccharide -induced macrophage TNF-alpha production, suggesting that MIC-1 acts in macrophages as an autocrine regulatory molecule, Its production in response to secreted proinflammatory cytokines and TGF-beta may serve to limit the later phases of macrophage activation.
Keyword Transforming Growth-Factor
Serum-Free System
Complementary-Dna
Gene Family
Expression
Identification
Differentiation
Interleukin-10
Receptors
Antibody
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: ResearcherID Downloads - Archived
 
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