This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jenkins, B. J.
Right arrow Articles by Ernst, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jenkins, B. J.
Right arrow Articles by Ernst, M.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, February 2004, p. 1453-1463, Vol. 24, No. 4
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.4.1453-1463.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Imbalanced gp130-Dependent Signaling in Macrophages Alters Macrophage Colony-Stimulating Factor Responsiveness via Regulation of c-fms Expression

Brendan J. Jenkins,1* Dianne Grail,1 Melissa Inglese,1 Cathy Quilici,1 Steven Bozinovski,2 Peter Wong,3 and Matthias Ernst1

Ludwig Institute for Cancer Research, Colon Molecular and Cell Biology Laboratory,1 The Walter and Eliza Hall Institute for Medical Research,3 Pharmacology Department, University of Melbourne, Parkville, Victoria, Australia2

Received 21 May 2003/ Returned for modification 30 July 2003/ Accepted 7 November 2003

The mechanisms by which interleukin-6 (IL-6) family cytokines, which utilize the common receptor signaling subunit gp130, influence monocyte/macrophage development remain unclear. Here we have utilized macrophages devoid of either gp130-dependent STAT1/3 (gp130{Delta}STAT/{Delta}STAT) or extracellular signal-regulated kinases 1 and 2 (ERK1/2) mitogen-activated protein (MAP) kinase (gp130Y757F/Y757F) activation to assess the individual contribution of each pathway to macrophage formation. While the inhibition by IL-6 of macrophage colony-stimulating factor (M-CSF)-induced colony formation observed in gp130wt/wt mice was abolished in gp130{Delta}STAT/{Delta}STAT mice, inhibition of macrophage colony formation was enhanced in gp130Y757F/Y757F mice. In gp130{Delta}STAT/{Delta}STAT bone marrow-derived macrophages (BMMs), both IL-6- and M-CSF-induced ERK1/2 tyrosine phosphorylation was enhanced. By contrast, tyrosine phosphorylation of ERK1/2 in response to M-CSF was reduced in gp130Y757F/Y757F BMMs, and the pattern of ERK1/2 activation in gp130 mutant BMMs correlated with their opposing responsiveness to M-CSF-induced proliferation. When compared to the level of expression in gp130wt/wt BMMs, c-fms expression was elevated in gp130{Delta}STAT/{Delta}STAT BMMs but reduced in gp130Y757F/Y757F BMMs. Finally, an ERK1/2 inhibitor suppressed M-CSF-induced BMM proliferation, and this result corresponded to a reduction in c-fms expression. Collectively, these results provide a functional and causal correlation between gp130-dependent ERK MAP kinase signaling and c-fms gene activation, a finding that provides a potential mechanism underlying the inhibition of M-CSF-dependent macrophage development by IL-6 family cytokines in mice.


* Corresponding author. Mailing address: Ludwig Institute for Cancer Research, Colon Molecular and Cell Biology Laboratory, P. O. Box 2008, Royal Melbourne Hospital, Victoria 3050, Australia. Phone: 61 3 9341 3155. Fax: 61 3 9341 3104. E-mail: Brendan.Jenkins{at}ludwig.edu.au.


Molecular and Cellular Biology, February 2004, p. 1453-1463, Vol. 24, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.4.1453-1463.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Hams, E., Colmont, C. S., Dioszeghy, V., Hammond, V. J., Fielding, C. A., Williams, A. S., Tanaka, M., Miyajima, A., Taylor, P. R., Topley, N., Jones, S. A. (2008). Oncostatin M Receptor-{beta} Signaling Limits Monocytic Cell Recruitment in Acute Inflammation. J. Immunol. 181: 2174-2180 [Abstract] [Full Text]  
  • Horan, K. A., Watanabe, K.-i., Kong, A. M., Bailey, C. G., Rasko, J. E. J., Sasaki, T., Mitchell, C. A. (2007). Regulation of Fc{gamma}R-stimulated phagocytosis by the 72-kDa inositol polyphosphate 5-phosphatase: SHIP1, but not the 72-kDa 5-phosphatase, regulates complement receptor 3 mediated phagocytosis by differential recruitment of these 5-phosphatases to the phagocytic cup. Blood 110: 4480-4491 [Abstract] [Full Text]  
  • Jenkins, B. J., Roberts, A. W., Greenhill, C. J., Najdovska, M., Lundgren-May, T., Robb, L., Grail, D., Ernst, M. (2007). Pathologic consequences of STAT3 hyperactivation by IL-6 and IL-11 during hematopoiesis and lymphopoiesis. Blood 109: 2380-2388 [Abstract] [Full Text]  
  • Jones, S. A. (2005). Directing Transition from Innate to Acquired Immunity: Defining a Role for IL-6. J. Immunol. 175: 3463-3468 [Abstract] [Full Text]  
  • Fielding, C. A., McLoughlin, R. M., Colmont, C. S., Kovaleva, M., Harris, D. A., Rose-John, S., Topley, N., Jones, S. A. (2005). Viral IL-6 Blocks Neutrophil Infiltration during Acute Inflammation. J. Immunol. 175: 4024-4029 [Abstract] [Full Text]  
  • McLoughlin, R. M., Jenkins, B. J., Grail, D., Williams, A. S., Fielding, C. A., Parker, C. R., Ernst, M., Topley, N., Jones, S. A. (2005). IL-6 trans-signaling via STAT3 directs T cell infiltration in acute inflammation. Proc. Natl. Acad. Sci. USA 102: 9589-9594 [Abstract] [Full Text]  
  • Jenkins, B. J., Roberts, A. W., Najdovska, M., Grail, D., Ernst, M. (2005). The threshold of gp130-dependent STAT3 signaling is critical for normal regulation of hematopoiesis. Blood 105: 3512-3520 [Abstract] [Full Text]