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Lipopolysaccharide and platelet-activating factor stimulate expression of platelet-activating factor acetylhydrolase via distinct signaling pathways

Inflammation Research volume 60, pages 735–744 (2011)Cite this article

Abstract

Objectives

This study was designed to investigate and characterize the ability of platelet-activating factor (PAF) to induce the expression of platelet-activating factor acetylhydrolase (PAF-AH).

Methods

Ribonuclease protection assays and quantitative real-time PCR were used to investigate the ability of lipopolysaccharide (LPS) and PAF to regulate PAF-AH mRNA expression in human monocyte–macrophage 6 (MM6) cells. Pharmacological inhibitors of mitogen activated protein kinases (MAPK) and PAF receptor antagonists were used to investigate the mechanism of regulation of PAF-AH.

Results

PAF-AH mRNA levels were increased upon exposure to LPS or PAF in a dose-dependent manner. LPS elicited a more potent and rapid increase in PAF-AH expression than the PAF-stimulated response. However, when administered concomitantly, PAF augmented the LPS-stimulated response. LPS-stimulated PAF-AH expression was susceptible to partial inhibition by a p38 MAPK inhibitor and PAF receptor antagonists. PAF-induced up-regulation of PAF-AH levels was solely mediated via the PAF receptor and was p38 MAPK-independent.

Conclusion

The proinflammatory mediators, LPS and PAF, increased levels of PAF-AH mRNA via distinct signaling pathways.

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Acknowledgments

We would like to express our sincere gratitude to Merle S. Olson, University of Texas Health Science Center, who donated much of the equipment to our laboratory to conduct this research. We would like to thank Ziming Cheng for technical help with the RPA assays and Drs. Gillian Galbraith and Barbara St Pierre Schneider for critically reading the manuscript. This work was supported by grants from the National Institutes of Health (HL66130) and the American Heart Association (0465061) to KMH.

Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Biomedical Sciences, University of Nevada Las Vegas School of Dental Medicine, 1001 Shadow Lane, Las Vegas, Nevada, 89106, USA

    Katherine M. Howard, Marcia Ditmyer & Nipa Patel

  2. Department of Chemistry, University of Nevada Las Vegas School of Dental Medicine, 1001 Shadow Lane, Las Vegas, Nevada, 89106, USA

    Mohammed Abdel-al

Authors
  1. Katherine M. Howard
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  2. Mohammed Abdel-al
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  3. Marcia Ditmyer
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  4. Nipa Patel
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Correspondence to Katherine M. Howard.

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Responsible Editor: Liwu Li.

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Howard, K.M., Abdel-al, M., Ditmyer, M. et al. Lipopolysaccharide and platelet-activating factor stimulate expression of platelet-activating factor acetylhydrolase via distinct signaling pathways. Inflamm. Res. 60, 735–744 (2011). https://doi.org/10.1007/s00011-011-0326-5

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  • DOI: https://doi.org/10.1007/s00011-011-0326-5

Keywords

  • PAF acetylhydrolase
  • Regulation
  • Lipopolysaccharide
  • Mitogen activated protein kinase
  • PAF receptor

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