HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mazzi, P. Articles by Dusi, S. Search for Related Content PubMed PubMed Citation Articles by Mazzi, P. Articles by Dusi, S. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB L-SERINE

IFN- Induces gp91^phox Expression in Human Monocytes via Protein Kinase C-Dependent Phosphorylation of PU.1¹

Paola Mazzi^*, Marta Donini^*, Daniela Margotto^*, Frans Wientjes and Stefano Dusi^2,*

^* Department of Pathology, Section of General Pathology, University of Verona, Verona, Italy; and Department of Medicine, University College London, The Rayne Institute, London, United Kingdom

We previously reported that the stimulation of human blood monocytes with IFN- induces the binding of PU.1 to the gp91^phox promoter and the consequent expression of gp91^phox. In this study, we show that the effect of IFN- is reproduced by the serine phosphatase inhibitor, okadaic acid, and this suggests that serine kinases could be involved in gp91^phox expression. We also show that IFN- induces the serine/threonine phosphorylation of PU.1 in cultured monocytes. This phosphorylation, as well as the IFN--induced PU.1 binding and gp91^phox protein synthesis, is slightly affected by the casein kinase II inhibitor, daidzein, but is abrogated by the protein kinase C (PKC) - and - inhibitor, Go6976, and by synthetic peptides with sequences based on the endogenous pseudosubstrate region of the classical PKC and isoforms. In contrast, peptides reproducing the pseudosubstrate region of PKC were without effect. Moreover, we found that the treatment of monocytes with IFN- induces the nuclear translocation and the activation of PKC and I, but not of PKC II, and that the IFN--induced phosphorylation of PU.1 was greatly reduced by LY333531, a selective inhibitor of PKC isoforms. Finally, nuclear run-on assays demonstrated that while the PKC inhibitors, Go6976 and LY333531, decrease the IFN--induced gp91^phox transcription, the serine phosphatase inhibitor, okadaic acid, enhances the gp91^phox gene transcription. Our results indicate that in cultured monocytes, IFN- induces the binding of PU.1 to the gp91^phox promoter and the expression of gp91^phox by phosphorylation of PU.1 via activation of PKC and/or I.

This article has been cited by other articles:

				R. Vasko, M. Koziolek, M. Ikehata, M. P. Rastaldi, K. Jung, H. Schmid, M. Kretzler, G. A. Muller, and F. Strutz Role of basic fibroblast growth factor (FGF-2) in diabetic nephropathy and mechanisms of its induction by hyperglycemia in human renal fibroblasts Am J Physiol Renal Physiol, June 1, 2009; 296(6): F1452 - F1463. [Abstract] [Full Text] [PDF]

				K. E. Van Zandt, F. B. Sow, W. C. Florence, B. S. Zwilling, A. R. Satoskar, L. S. Schlesinger, and W. P. Lafuse The iron export protein ferroportin 1 is differentially expressed in mouse macrophage populations and is present in the mycobacterial-containing phagosome J. Leukoc. Biol., September 1, 2008; 84(3): 689 - 700. [Abstract] [Full Text] [PDF]

				L. Pearn, J. Fisher, A. K. Burnett, and R. L. Darley The role of PKC and PDK1 in monocyte lineage specification by Ras Blood, May 15, 2007; 109(10): 4461 - 4469. [Abstract] [Full Text] [PDF]

				J. Zou, A. Carrington, B. Collet, J. M. Dijkstra, Y. Yoshiura, N. Bols, and C. Secombes Identification and Bioactivities of IFN-{gamma} in Rainbow Trout Oncorhynchus mykiss: The First Th1-Type Cytokine Characterized Functionally in Fish J. Immunol., August 15, 2005; 175(4): 2484 - 2494. [Abstract] [Full Text] [PDF]

				H. Zhong, A. Takeda, R. Nazari, H. Shio, G. Blobel, and N. R. Yaseen Carrier-independent Nuclear Import of the Transcription Factor PU.1 via RanGTP-stimulated Binding to Nup153 J. Biol. Chem., March 18, 2005; 280(11): 10675 - 10682. [Abstract] [Full Text] [PDF]