Captopril-impaired production of tumor necrosis factor-alpha-induced interleukin-1beta in human monocytes is associated with altered intracellular distribution of nuclear factor-kappaB.
We evaluated the effects of the angiotensin-converting enzyme (ACE) inhibitor captopril on pathways for monocyte production of interleukin (IL)-1beta in vitro. Human monocytes were treated with captopril and stimulated with tumor necrosis factor (TNF)-alpha or lipopolysaccharide. Captopril caused a dose-dependent reduction of TNF-alpha induced IL-1beta. LPS-induced IL-1beta generation was not reduced by the ACE inhibitor. Pro-IL-1beta concentrations followed the same pattern as that for mature IL-1beta when monocytes were preincubated with captopril. Also, IL-1beta mRNA concentrations were reduced by captopril pretreatment in parallel with IL-1beta. We sought to determine whether captopril affected the nuclear factor (NF)-kappaB complex in monocytic cells. We found that the translocation of the p-65 component of NF-kappaB to the nucleus was inhibited by captopril. Thus captopril reduced TNF-alpha-induced IL-1beta and IL-1betamRNA synthesis in monocytes, in vitro, probably through interference with NF-kappaB activation of the IL-1beta gene. These results support the hypothesis that captopril has immunomodulating properties.
Andersson
Patrik
P
Center for Inflammatory and Hematology Research, Karolinska Institutet, Stockholm, Sweden.
Cederholm
Tommy
T
Johansson
Anne-Sofie
AS
Palmblad
Jan
J
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics* / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D020298:U937 Cells
D000806:Angiotensin-Converting Enzyme Inhibitors; D000970:Antineoplastic Agents; D007375:Interleukin-1; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D002216:Captopril