Mediators of Inflammation

Mediators of Inflammation / 1996 / Article

Open Access

Volume 5 |Article ID 129686 | https://doi.org/10.1155/S0962935196000580

A. Hichami, E. Boichot, N. Germain, E. Berdyshev, O. Coqueret, V. Lagente, "Phosphodiesterase 4 inhibitors and db-cAMP inhibit TNF-α release from human mononuclear cells. Effects of cAMP and cGMP-dependent protein kinase inhibitors", Mediators of Inflammation, vol. 5, Article ID 129686, 4 pages, 1996. https://doi.org/10.1155/S0962935196000580

Phosphodiesterase 4 inhibitors and db-cAMP inhibit TNF-α release from human mononuclear cells. Effects of cAMP and cGMP-dependent protein kinase inhibitors

Abstract

We investigated the effects of specific inhibitors of cAMP-dependent protein kinase (PKA) and cGMP-dependent protein kinase (PKG) on the inhibitory activity of phosphodiesterase (PDE) type 4 inhibitors and of the cell permeable analogue of cAMP, db-cAMP on LPS-induced TNF-α release from human mononuclear cells. Incubation from 30 min of mononuclear cells with dbcAMP (10−5 to 10−3 M), rolipram (10−9 M to 10−5 M) or Ro 20-1724 (10−9 M to 10−5 M) significantly inhibited LPS-induced TNF-α release. When mononuclear cells were preincubated for 30 min with the selective PKA inhibitor, H89 (10−4 M), but not with the selective PKG inhibitor, Rp-8-pCPT-cGMPs (10−4 M), a significant reduction of the inhibitory effect of db-cAMP was noted. Thirty min incubation of mononuclear cells with Rp-8-pCPT-cGMPs induced a significant reduction of the inhibitory activities of both rolipram and Ro 20-1724 (10−9 to 10−5 M) on LPS-induced TNF-α release, whereas H89 elicited a moderate, but significant inhibition. The present data indicate that db-cAMP inhibits TNF-α release from human mononuclear cells through a PKA-dependent mechanism. In contrast, PDE 4 inhibitors elicit their in vitro anti-inflammatory activities via a PKG-dependent rather than PKA-dependent activation.

Copyright © 1996 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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