A Cofactor of mRNA Synthetase, p43, Is Secreted to Up-regulate Proinflammatory Genes

Young-Gyu Ko, Heonyong Park, Taeho Kim, Joong Won Lee, Sang Gyu Park, Wongi Seol, Jee Eun Kim, Won Ha Lee, Se Hwa Kim, Jeong Euy Park, Sunghoon Kim

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

An auxiliary factor of mammalian multi-aminoacyl-tRNA synthetases, p43, is thought to be a precursor of endothelial monocyte-activating polypeptide II (EMAP II) that triggers proinflammation in leukocytes and macrophages. In the present work, however, we have shown that p43 itself is specifically secreted from intact mammalian cells, while EMAP II is released only when the cells are disrupted. Secretion of p43 was also observed when its expression was increased. These results suggest that p43 itself should be a real cytokine secreted by an active mechanism. To determine the cytokine activity and active domain of p43, we investigated tumor necrosis factor (TNF) and interleukin-8 (IL-8) production from human monocytic THP-1 cells treated with various p43 deletion mutants. The full length of p43 showed higher cytokine activity than EMAP II, further supporting p43 as the active cytokine. p43 was also shown to activate MAPKs and NFκB, and to induce cytokines and chemokines such as TNF, IL-8, MCP-1, MIP-1α, MIP-1β, MIP-2α, IL-1β, and RANTES. Interestingly, the high level of p43 was observed in the foam cells of atherosclerotic lesions. Therefore, p43 could be a novel mediator of atherosclerosis development as well as other inflammation-related diseases.

Original languageEnglish
Pages (from-to)23028-23033
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number25
DOIs
Publication statusPublished - 2001 Jun 22
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

Fingerprint Dive into the research topics of 'A Cofactor of mRNA Synthetase, p43, Is Secreted to Up-regulate Proinflammatory Genes'. Together they form a unique fingerprint.

  • Cite this

    Ko, Y-G., Park, H., Kim, T., Lee, J. W., Park, S. G., Seol, W., Kim, J. E., Lee, W. H., Kim, S. H., Park, J. E., & Kim, S. (2001). A Cofactor of mRNA Synthetase, p43, Is Secreted to Up-regulate Proinflammatory Genes. Journal of Biological Chemistry, 276(25), 23028-23033. https://doi.org/10.1074/jbc.M101544200