Lipopolysaccharide administration in vivo induces differential expression of cAMP-specific phosphodiesterase 4B mRNA splice variants in the mouse brain
J. Neurosci. Res.. 2011-07-11; 89(11): 1761-1772
DOI: 10.1002/jnr.22707
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Many inflammatory processes involve cAMP. Pharmacological manipulation of cAMP
levels using specific phosphodiesterase (PDE) inhibitors provokes an
antiinflammatory response. The aim of this study was to investigate changes in
the pattern and levels of expression of mRNAs coding for the cAMP-specific PDE4
family and subfamilies in mouse brain during the immediate acute immune response
provoked by an intraperitoneal injection of lipopolysaccharide (LPS). PDE4B, and
furthermore the splice variants PDE4B2 and PDE4B3, were the only mRNAs that
showed altered expression. Whereas PDE4B2 presented increased expression at both
3 and 8 hr postinjection, PDE4B3 mRNA showed decreased expression that reached a
minimum 8 hr postinjection. PDE4B2 mRNA upregulation was observed mainly in
endothelial and macrophage/neutrophil cell populations in the leptomeninges, and
the downregulation of PDE4B3 was observed mainly in oligodendrocytes throughout
the brain. Our results clearly illustrate the distinctive anatomical distribution
and cellular localization of the PDE4Bs during neuroinflammation and emphasize
the importance of PDE4B splice-variant-specific inhibitors as therapeutic tools.
Copyright © 2011 Wiley-Liss, Inc.