Lipopolysaccharide-dependent interaction between PU.1 and cJun determines production of lipocalin-type prostaglandin D synthase and prostaglandin D2 in macrophages

Myungsoo Joo, Minjae Kwon, Yong Jig Cho, Ningning Hu, Tetyana V. Pedchenko, Ruxana T. Sadikot, Timothy S. Blackwell, John W. Christman

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Previously, we reported that expression of lipocalin-prostaglandin D synthase (L-PGDS) is inducible in macrophages and protects from Pseudomonas pneumonia. Here, we investigated the mechanism by which L-PGDS gene expression is induced in macrophages. A promoter analysis of the murine L-PGDS promoter located a binding site of PU.1, a transcription factor essential for macrophage development and inflammatory gene expression. A chromatin immunoprecipitation assay showed that PU.1 bound to the cognate site in the endogenous L-PGDS promoter in response to LPS. Overexpression of PU.1, but not of PU.1 S148A, a mutant inert to casein kinase II (CKII) or NF-κB-inducing kinase (NIK), induced L-PGDS in RAW 264.7 cells. Conversely, siRNA silencing of PU.1 expression blunted productions of L-PGDS and prostaglandin D2 (PGD2). LPS treatment induced formation of the complex of PU.1 and cJun on the PU.1 site, but inactivation of cJun by treatment with JNK or p38 kinase inhibitor abolished the complex, and suppressed PU.1 transcriptional activity for L-PGDS gene expression. Together, these results show that PU.1, activated by CKII or NIK, cooperates with MAPK-activated cJun to maximally induce L-PGDS expression in macrophages following LPS treatment, and suggest that PU.1 participates in innate immunity through the production of L-PGDS and PGD2.

Original languageEnglish (US)
Pages (from-to)L771-L779
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume296
Issue number5
DOIs
StatePublished - May 2009
Externally publishedYes

Keywords

  • Gene regulation
  • Inflammation
  • Prostaglandin
  • Transcription factors

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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