Interleukin-11 attenuates human vascular smooth muscle cell proliferation.
Interleukin (IL)-11 is a growth factor for megakaryocytes, osteoclasts, and intestinal mucosa. IL-11 is also an anti-inflammatory agent, mediating many of its effects by inhibition of the transcriptional activator nuclear factor (NF)-kappa B. The purposes of this study were to examine the effects of IL-11 on human vascular smooth muscle cell (VSMC) proliferation and NF-kappa B activity. VSMC were cultured from human transplant donor aortas, stimulated with basic fibroblastic growth factor (bFGF), and treated with IL-11. VSMC stimulated with bFGF demonstrated an increase in cell number by direct cell counting and mitochondrial activity. IL-11 caused a concentration-dependent decrease in bFGF-induced VSMC proliferation. Furthermore, IL-11 attenuated bFGF-induced increases in cytoplasmic and intranuclear unbound NF-kappa B p65. Similarly, IL-11 attenuated VSMC expression of two NF-kappa B-dependent cytokines, IL-8 and IL-6. Stimulated VSMC did not secrete IL-11, suggesting that endogenous IL-11 did not account for our observations. In conclusion, IL-11 inhibits human VSMC proliferation in vitro and is associated with suppression of NF-kappa B.
Zimmerman
Michael A
MA
Division of Cardiothoracic Surgery, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Selzman
Craig H
CH
Reznikov
Leonid L
LL
Raeburn
Christopher D
CD
Barsness
Katherine
K
McIntyre
Robert C
RC
Hamiel
Christine R
CR
Harken
Alden H
AH
D001011:Aorta; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000032:analysis / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D051996:Transcription Factor RelA
D017370:Interleukin-11; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D051996:Transcription Factor RelA; D016222:Fibroblast Growth Factor 2