Other PDE4 isoforms expressed in macrophages (PDE4A and PDE4D) were not involved in the regulation of this response.
The generation of mice deficient in PDE4A, PDE4B, and PDE4D has been described previously.
Macrophages are known to express three PDE4 isoforms (PDE4A, 4B, and 4D) under a basal or LPS-stimulated condition.
[sup] Ablation of PDE4A or PDE4D has little or no effect on the CCL3 release.
Recently, authors suggested a relative selectivity of imperatorin as inhibitor within the PDE4 family, mainly for PDE4A
and PDE4B (Ivey et al., 2008; Pantel et al., 2011); this may be a mechanism responsible for the vasorelaxant effect induced by imperatorin; further work will be needed to establish this possibility.
Although PDE4A and PDE4D were significantly increased in the OVA+iBp rats, PDE4A did not increase in the OVA or iBprats, while simultaneous exposure to OVA and intramuscular iBpenhanced the PDE4A expression.
However, in the lungs of allergic rats, expression of the PDE4A and PDE4D genes, but not the PDE4B gene, was upregulated, suggesting that the expression of these genes might be induced by a mechanism(s) distinct from those cAMP or LPS mechanisms.
PDE4A is involved in the inflammatory process in airways .
Christensen et al., "Suppression of human inflammatory cell function by subtypeselective PDE4 inhibitors correlates with inhibition of PDE4A and PDE4B," The British Journal of Pharmacology, vol.
Among the PDE families, the PDE4 family, which includes four isoforms named PDE4A, -4B, -4C, and -4D, specifically hydrolyzes cAMP [10, 11].
Anti-PDE4 antibodies were purchased from Abcam (PDE4A: cat#: ab14607; PDE4B: cat#: ab14611; PDE4C: cat#: ab97356; PDE4D: cat#: ab14613, Abcam, Inc., Cambridge, MA, USA).
Immunoblotting for PDE4A, -4B, -4C, -4D and for [beta]-actin was carried out with whole cell lysates obtained from the cells pretreated with either PGE or indomethacin for 24 hrs.