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This Article Full Text Full Text (PDF) All Versions of this Article: 296/5/L771    most recent 90320.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Joo, M. Articles by Christman, J. W. Search for Related Content PubMed PubMed Citation Articles by Joo, M. Articles by Christman, J. W.

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

¹Division of Applied Medicine, School of Oriental Medicine, Pusan National University, Busan, Korea; ²Division of Allergy, Pulmonary, and Critical Care Medicine, ³Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee; and ⁴Section of Pulmonary, Critical Care, and Sleep Medicine, University of Illinois and the Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois

Submitted 21 May 2008 ; accepted in final form 18 January 2009

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-B-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.

prostaglandin; gene regulation; transcription factors; inflammation