Biomedical Engineering Reference
In-Depth Information
SVEC 4-10
SVEC 4-10
MLE-12
MLE-12
- +++++ - +++++
- -+-----+---
---+-----+--
- +++++ - +++++
HIMF (20nM)
nM)
LY294002 (10
M)
- -+-----+---
SB203580 (5
M)
---+-----+--
U0126 (5
M)
- ---+ -- ---+ -
- ---+ -- ---+ -
- ---- +- ---- +
M)
PD098099 (5
M)
- ---- +- ---- +
P-Akt Ser473
P-Akt Ser473
P-Akt Thr308
P-Akt Thr308
Akt
Akt
Fig. 5
HIMF stimulates Akt phosphorylation via PI3K activation. SVEC 4-10 and MLE-12 cells
were treated with HIMF and the Akt phosphorylation was examined with specii c antibodies for
Ser473 and h r308. h e results showed that HIMF-stimulated Akt phosphorylation is inhibited
by PI3K inhibitor LY294002, especially at h
r308. Reprint from Tong
et al.
(2006), with
permission.
dominant-negative mutant of PI-3K, into SVEC 4-10 and MLE-12 cells, abolished
HIMF-induced phosphorylation of IKK and IκBα and reduced the transcriptional
activities for NF-κB and VCAM-1
(Figs. 6 and 7)
, and the subsequent NF-
κB activation. h ese observations suggest that PI-3K/Akt pathway functions
upstream of NF-κB in responding to HIMF signals. Together, these data suggest
that the PI-3K/Akt pathway is involved in HIMF-mediated NF-κB activation and
the subsequent VCAM-1 production.
Applications to Other Areas of Health and Disease
h e signaling transduction pathways of PI3K and NF-κB play critical roles in
adhesion molecule gene expression, especially in leukocyte extravasation induced
by cytokine and inl ammatory agents. h e ubiquitous expression and coexistence of
the PI3K and NF-κB signaling pathways in both inl ammatory cells and in vascular
endothelial cells determines the potential interaction and crosstalk between the
two pathways in these cells and ensures there are coordinated responses to facilitate
precise migration of specialized leukocytes into the inl ammatory sites. Adhesion
molecule upregulation is not only an important process in inl ammatory response,
but also a crucial step for cardiovascular diseases and cancer. To fully understand
the molecular mechanisms of adhesion molecule expression under the controls of
the PI3K/Akt-NF-κB signaling will certainly be advantageous for the prevention
and treatment of these diseases in the future.
