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Interleukin-10 does not mediate the inhibitory effect of PDE-4 inhibitors and other cAMP-elevating drugs on lipopolysaccharide-induced tumors necrosis factor-alpha generation from human peripheral blood monocytes.
Cell Biochem Biophys 1998; 29(1-2):179-201CB

Abstract

Lipopolysaccharide (LPS)-induced liver injury in mice and LPS-induced tumor necrosis factor-alpha (TNF-alpha) generation by murine macrophages and hepatocytes are suppressed markedly by agents that elevate intracellular cAMP. Phosphodiesterase (PDE)-4 inhibitors, beta 2-adrenoceptor agonists, and E-series prostaglandins also attenuate the induction of the TNF-alpha gene in human monocytes in response to bacterial LPS. The mechanism of action of cAMP is unclear, but in the mouse, is believed to involve the generation of this anti-inflammatory cytokine, interleukin-10 (IL-10). In this article, we describe the results of studies designed to determine the extent to which IL-10 contributes to the suppression of TNF-alpha generation from LPS-stimulated human monocytes evoked by 8-bromo cyclic AMP (8-Br-cAMP), rolipram, salbutamol, and prostaglandin E2 (PGE2). LPS evoked a time- and concentration-dependent generation of TNF-alpha (t1/2 = 4.5 h; EC50 = 273 pg/mL), which was inhibited by exogenous human recombinant (h) IL-10 (IC50 = 124 pg/mL), and by rolipram (EC50 = 420 nM), 8-Br-cAMP (EC50 = 77 (microM), PGE2 (EC50 = 15 nM) and salbutamol (EC50 = 20 nM). In addition, 8-Br-cAMP, PGE2; and salbutamol (but not rolipram) augmented significantly LPS-induced IL-10 production (two-to-fivefold) under identical experimental conditions. Pretreatment of monocytes with an anti-IL-10 monoclonal antibody (MAb) that abolished the inhibitory action of a maximally effective concentration of exogenous hrIL-10, failed to attenuate the inhibitory effect of rolipram, PGE2, salbutamol, and 8-Br-cAMP. Anti-IL-10 was similarly inactive when the number of monocytes seeded was increased from 0.5 to 4 x 10(6)/mL or when measurements were made at 42 h post-LPS, a time when the concentration of IL-10 released was maximal. Collectively, these data suggest that in contrast to murine hepatocytes and macrophages, IL-10 does not mediate the inhibitory effect of cAMP-elevating drugs on TNF-alpha generation from human monocytes. Although the reason for this discrepancy is unclear, we suggest that the influence of cAMP on the transcriptional regulation of the TNF-alpha gene differs between species or when monocytes have differentiated into macrophages.

Authors+Show Affiliations

Imperial College School of Medicine, National Heart and Lung Institute, London.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9631245

Citation

Seldon, P M., et al. "Interleukin-10 Does Not Mediate the Inhibitory Effect of PDE-4 Inhibitors and Other cAMP-elevating Drugs On Lipopolysaccharide-induced Tumors Necrosis Factor-alpha Generation From Human Peripheral Blood Monocytes." Cell Biochemistry and Biophysics, vol. 29, no. 1-2, 1998, pp. 179-201.
Seldon PM, Barnes PJ, Giembycz MA. Interleukin-10 does not mediate the inhibitory effect of PDE-4 inhibitors and other cAMP-elevating drugs on lipopolysaccharide-induced tumors necrosis factor-alpha generation from human peripheral blood monocytes. Cell Biochem Biophys. 1998;29(1-2):179-201.
Seldon, P. M., Barnes, P. J., & Giembycz, M. A. (1998). Interleukin-10 does not mediate the inhibitory effect of PDE-4 inhibitors and other cAMP-elevating drugs on lipopolysaccharide-induced tumors necrosis factor-alpha generation from human peripheral blood monocytes. Cell Biochemistry and Biophysics, 29(1-2), pp. 179-201.
Seldon PM, Barnes PJ, Giembycz MA. Interleukin-10 Does Not Mediate the Inhibitory Effect of PDE-4 Inhibitors and Other cAMP-elevating Drugs On Lipopolysaccharide-induced Tumors Necrosis Factor-alpha Generation From Human Peripheral Blood Monocytes. Cell Biochem Biophys. 1998;29(1-2):179-201. PubMed PMID: 9631245.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interleukin-10 does not mediate the inhibitory effect of PDE-4 inhibitors and other cAMP-elevating drugs on lipopolysaccharide-induced tumors necrosis factor-alpha generation from human peripheral blood monocytes. AU - Seldon,P M, AU - Barnes,P J, AU - Giembycz,M A, PY - 1998/6/19/pubmed PY - 1998/6/19/medline PY - 1998/6/19/entrez SP - 179 EP - 201 JF - Cell biochemistry and biophysics JO - Cell Biochem. Biophys. VL - 29 IS - 1-2 N2 - Lipopolysaccharide (LPS)-induced liver injury in mice and LPS-induced tumor necrosis factor-alpha (TNF-alpha) generation by murine macrophages and hepatocytes are suppressed markedly by agents that elevate intracellular cAMP. Phosphodiesterase (PDE)-4 inhibitors, beta 2-adrenoceptor agonists, and E-series prostaglandins also attenuate the induction of the TNF-alpha gene in human monocytes in response to bacterial LPS. The mechanism of action of cAMP is unclear, but in the mouse, is believed to involve the generation of this anti-inflammatory cytokine, interleukin-10 (IL-10). In this article, we describe the results of studies designed to determine the extent to which IL-10 contributes to the suppression of TNF-alpha generation from LPS-stimulated human monocytes evoked by 8-bromo cyclic AMP (8-Br-cAMP), rolipram, salbutamol, and prostaglandin E2 (PGE2). LPS evoked a time- and concentration-dependent generation of TNF-alpha (t1/2 = 4.5 h; EC50 = 273 pg/mL), which was inhibited by exogenous human recombinant (h) IL-10 (IC50 = 124 pg/mL), and by rolipram (EC50 = 420 nM), 8-Br-cAMP (EC50 = 77 (microM), PGE2 (EC50 = 15 nM) and salbutamol (EC50 = 20 nM). In addition, 8-Br-cAMP, PGE2; and salbutamol (but not rolipram) augmented significantly LPS-induced IL-10 production (two-to-fivefold) under identical experimental conditions. Pretreatment of monocytes with an anti-IL-10 monoclonal antibody (MAb) that abolished the inhibitory action of a maximally effective concentration of exogenous hrIL-10, failed to attenuate the inhibitory effect of rolipram, PGE2, salbutamol, and 8-Br-cAMP. Anti-IL-10 was similarly inactive when the number of monocytes seeded was increased from 0.5 to 4 x 10(6)/mL or when measurements were made at 42 h post-LPS, a time when the concentration of IL-10 released was maximal. Collectively, these data suggest that in contrast to murine hepatocytes and macrophages, IL-10 does not mediate the inhibitory effect of cAMP-elevating drugs on TNF-alpha generation from human monocytes. Although the reason for this discrepancy is unclear, we suggest that the influence of cAMP on the transcriptional regulation of the TNF-alpha gene differs between species or when monocytes have differentiated into macrophages. SN - 1085-9195 UR - https://www.unboundmedicine.com/medline/citation/9631245/Interleukin_10_does_not_mediate_the_inhibitory_effect_of_PDE_4_inhibitors_and_other_cAMP_elevating_drugs_on_lipopolysaccharide_induced_tumors_necrosis_factor_alpha_generation_from_human_peripheral_blood_monocytes_ L2 - https://dx.doi.org/10.1007/BF02737835 DB - PRIME DP - Unbound Medicine ER -