Title

A novel CCCH-zinc finger protein family regulates proinflammatory activation of macrophages

Authors

Authors

J. Liang; J. Wang; A. Azfer; W. Song; G. Tromp; P. E. Kolattukudy;M. Fu

Comments

Authors: contact us about adding a copy of your work at STARS@ucf.edu

Abbreviated Journal Title

J. Biol. Chem.

Keywords

NF-KAPPA-B; MESSENGER-RNA; TRISTETRAPROLIN; LIPOPOLYSACCHARIDE; ALPHA; CELLS; UBIQUITINATION; AUTOIMMUNITY; INHIBITION; ARTHRITIS; Biochemistry & Molecular Biology

Abstract

Activated macrophages play an important role in many inflammatory diseases. However, the molecular mechanisms controlling macrophage activation are not completely understood. Here we report that a novel CCCH-zinc finger protein family, MCPIP1, 2, 3, and 4, encoded by four genes, Zc3h12a, Zc3h12b, Zc3h12c, and Zc3h12d, respectively, regulates macrophage activation. Northern blot analysis revealed that the expression of MCPIP1 and MCPIP3 was highly induced in macrophages in response to treatment with lipopolysaccharide (LPS). Although not affecting cell surface marker expression and phagocytotic function, overexpression of MCPIP1 significantly blunted LPS-induced inflammatory cytokine and NO(2)radical anion. production as well as their gene expression. Conversely, short interfering RNA-mediated reduction in MCPIP1 augmented LPS-induced inflammatory gene expression. Further studies demonstrated that MCPIP1 did not directly affect the mRNA stability of tumor necrosis factor alpha and monocyte chemoattractant protein 1 (MCP-1) but strongly inhibited LPS-induced tumor necrosis factor alpha and inducible nitric-oxide synthase promoter activation. Moreover, we found that forced expression of MCPIP1 significantly inhibited LPS-induced nuclear factor-kappa B activation. These results identify MCP-induced proteins, a novel CCCH-zinc finger protein family, as negative regulators in macrophage activation and may implicate them in host immunity and inflammatory diseases.

Journal Title

Journal of Biological Chemistry

Volume

283

Issue/Number

10

Publication Date

1-1-2008

Document Type

Article

Language

English

First Page

6337

Last Page

6346

WOS Identifier

WOS:000253779500041

ISSN

0021-9258

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