Article Text

PDF
OP0252 Modulation of pro-inflammatory response of monocytes by glucocorticoids
  1. K.J. Barczyk1,
  2. Y. Fleischer1,
  3. J. Ehrchen2,
  4. J. Roth1
  1. 1Institute of Immunology
  2. 2Dept. of Dermatology, University Hospital Münster, Muenster, Germany

Abstract

Background Active resolution of inflammation is a previously unrecognized process essential for tissue homeostasis1. Monocytes and macrophages are the central component of the immune system critical not only for initiation and maintenance of the immune response but also for the resolution of inflammation. Glucocorticoids (GC) are still the most widely used anti-inflammatory agents acting on many targets in a cell-specific manner, including monocytes and macrophages2. We previously demonstrated that the treatment of monocytes with GC does not suppress monocytes functions, but rather induces specific differentiation of cells with anti-inflammatory phenotype3,4. Nevertheless the mechanism of GC action on monocytes during inflammation is currently not well defined.

Objectives The aim of our studies was to investigate the effects of GC on pro-inflammatory monocytes.

Methods GC-, LPS- and GC-LPS-induced gene expression patterns in monocytes were analysed by microarray technology. The results were independently confirmed by real-time PCR. Protein expression and activation was analysed by Western Blot and Flow Cytometry. Monocyte functions pivotal for innate immunity – migration, chemotaxis, phagocytosis, killing, oxidative burst – were assessed.

Results As expected, treatment of LPS-stimulated monocytes with GC resulted in inhibited expression of many of pro-inflammatory factors. Nevertheless, many of them have not been described to be regulated by GC in monocytes so far. Surprisingly, we have found that GC-LPS treatment of monocytes led also to synergistical up-regulation of many genes, which are not induced by GC or LPS alone. Moreover, we observed additive effects of GC and LPS on expression of many anti-inflammatory genes which was much more pronounced compared to monocytes stimulated with GC alone. Analysis of specific functions of monocytes have shown that GC-LPS treatment inhibited specifically monocyte adherence, but enhanced spontaneous migration, chemotaxis, phagocytosis and killing of pathogens, and engulfment of apoptotic cells as well as the ability to produce anti-inflammatory lipid mediators.

Conclusions Our results demonstrate that GC do not simply suppress LPS-mediated activation of monocytes, but rather induce their re-programming toward a specific anti-inflammatory phenotype involved in resolution of inflammation. Interestingly, this anti-inflammatory phenotype is not associated with reduced but rather with enhanced anti-microbial activity. Unravelling specific GC-actions on monocytes may thus define novel pathways allowing anti-inflammatory therapy without enhanced risk for severe infections.

  1. Serhan et al. FASEB J. 2007, 21:325-332.

  2. Buttgereit et al. Arthritis Rheum. 2004, 50:3408-3417.

  3. Ehrchen et al. Blood 2007, 109:1265-1274.

  4. Barczyk et al. Blood 2010, 116: 446-455.

Disclosure of Interest None Declared

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.