TY - JOUR
T1 - An IκB-α mutant inhibits cytokine gene expression and proliferation in human vascular smooth muscle cells
AU - Wang, Zhongbiao
AU - Castresana, Manuel R.
AU - Detmer, Kristina
AU - Newman, Walter H.
N1 - Funding Information:
This work was supported by grants from the MedCen Foundation, the Clinical Research Center of the Medical Center of Central Georgia. The authors acknowledge the expert technical assistance of Parrish Mitchell.
PY - 2002
Y1 - 2002
N2 - Background. Inflammatory reaction and intimal proliferation of smooth muscle cells are characteristics of vascular stenotic lesions. Nuclear factor κB (NF-κB) is involved in regulation of inflammation and cell survival in a variety of cell types. We tested a hypothesis that selective inhibition of NF-κB by expression of a mutated, nondegradable inhibitor of NF-κB, IκB-αM, would inhibit proinflammatory cytokine expression and proliferation in human vascular smooth muscle cell. Materials and methods. Smooth muscle cells were cultured from internal mammary artery and infected with recombinant adenovirus vectors. Results. Adenoviral expression of IκB-αM inhibited diverse signal-triggered cellular IκB-α degradation, subsequent NF-κB activation, and transactivation of proinflammatory cytokine genes. Expression of IκB-αM in low-density VSMC led to a 60% reduction in serum-stimulated cell growth and a 10% increment in apoptotic incidence but was without effect in high-density cultures. Coexpression of NF-κB p65 attenuated apoptosis in low-density cells induced by IκB-αM. Therefore, the susceptibility to apoptosis induction in the low-density cells correlated with lower constitutive NF-κB activity. The induction of apoptosis by IκB-αM and the rescue by NF-κB p65 might be explained by mutual control of NF-κB p65 and IκB-αM access to the nucleus. Conclusion. Our results suggest that expression of nondegradable IκB-α might have therapeutic potential in both vascular inflammatory reaction and smooth muscle cell proliferation.
AB - Background. Inflammatory reaction and intimal proliferation of smooth muscle cells are characteristics of vascular stenotic lesions. Nuclear factor κB (NF-κB) is involved in regulation of inflammation and cell survival in a variety of cell types. We tested a hypothesis that selective inhibition of NF-κB by expression of a mutated, nondegradable inhibitor of NF-κB, IκB-αM, would inhibit proinflammatory cytokine expression and proliferation in human vascular smooth muscle cell. Materials and methods. Smooth muscle cells were cultured from internal mammary artery and infected with recombinant adenovirus vectors. Results. Adenoviral expression of IκB-αM inhibited diverse signal-triggered cellular IκB-α degradation, subsequent NF-κB activation, and transactivation of proinflammatory cytokine genes. Expression of IκB-αM in low-density VSMC led to a 60% reduction in serum-stimulated cell growth and a 10% increment in apoptotic incidence but was without effect in high-density cultures. Coexpression of NF-κB p65 attenuated apoptosis in low-density cells induced by IκB-αM. Therefore, the susceptibility to apoptosis induction in the low-density cells correlated with lower constitutive NF-κB activity. The induction of apoptosis by IκB-αM and the rescue by NF-κB p65 might be explained by mutual control of NF-κB p65 and IκB-αM access to the nucleus. Conclusion. Our results suggest that expression of nondegradable IκB-α might have therapeutic potential in both vascular inflammatory reaction and smooth muscle cell proliferation.
KW - Apoptosis
KW - Cell growth
KW - Cytokine gene expression
KW - Nuclear factor-κB
KW - Vascular smooth muscle cells
KW - Viral-mediated gene transfer
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U2 - 10.1006/jsre.2001.6320
DO - 10.1006/jsre.2001.6320
M3 - Article
C2 - 11796019
AN - SCOPUS:0036024969
SN - 0022-4804
VL - 102
SP - 198
EP - 206
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 2
ER -