sup][17],[21],[22] The PDE4A and PDE4B null mice have been backcrossed from the mixed 129/Ola x C57Bl/6 to the pure C57BL/6 background for at least 12 generations, whereas the PDE4D mice were kept in the mixed background because the PDE4D null mice become embryonic lethal when the null allele is transferred to the pure C57Bl/6 background.
01), exerting 62% decrease compared to the PDE4B [sup]+/+ macrophages.
sup][5] To determine whether these signal pathways mediate the effect of PDE4 inhibitors or PDE4B ablation on CCL3 production, mouse peritoneal macrophages were stimulated with LPS in the presence of the cAMP analog dibutyryl-cAMP (db-cAMP), the Epac activator 8-pCPT-2′-O-Me-cAMP or the PKA activator 6-Bnz-cAMP.
Of the three proteins identified, TNF-a regulation by PDE4B has been studied extensively, [sup][12],[13],[14],[15],[16] whereas the information on CCL3 and IL-1Ra regulation by PDE4 subtypes remains largely unclear.
These results resemble our previous findings that of the three PDE4 subtypes, only PDE4B ablation suppresses LPS-induced TNF-a production, [sup][18] suggesting that the expression of both TNF-a and CCL3 in macrophages is triggered by the same TLR signal pathways and modulated by PDE4B or cAMP signaling in a similar fashion.
Like its impact on TNF-a production, ablation or inactivation of PDE4B also suppressed LPS-induced CCL3 production in macrophages.
