Figure 4.
Figure 4. rhMIF induces MN ICAM-1 up-regulation via Src kinase, PI3K, and NFκB. (A) To investigate the signaling cascades involved in ICAM-1 up-regulation by rhMIF, we performed cell-surface ELISAs using chemical signaling inhibitors. rhMIF-increased ICAM-1 expression was significantly inhibited by an Src inhibitor, PP2, a PI3K inhibitor, LY, and a NFκB inhibitor, PDTC, (*P < .05) but not by a Jak2 inhibitor, AG-490, suggesting that rhMIF induces ICAM-1 expression in MNs via Src, PI3K, and NFκB. rhMIF induced a 3-fold increase in MN ICAM-1 expression compared with NS. (B) rhMIF-induced ICAM-1 expression was significantly decreased by antisense ODNs of Src, PI3K, and NFκB compared with MNs transfected with sense ODNs of Src, PI3K, and NFκB in 8 to 12 hours (*P < .05). Panel B shows the percentage of inhibition in ICAM-1 expression by antisense ODNs of Src, PI3K, and NFκB compared with corresponding sense ODNs. Data represent the mean of 3 individual experiments (n) ± SEM. *P < .05 was considered significant.

rhMIF induces MN ICAM-1 up-regulation via Src kinase, PI3K, and NFκB. (A) To investigate the signaling cascades involved in ICAM-1 up-regulation by rhMIF, we performed cell-surface ELISAs using chemical signaling inhibitors. rhMIF-increased ICAM-1 expression was significantly inhibited by an Src inhibitor, PP2, a PI3K inhibitor, LY, and a NFκB inhibitor, PDTC, (*P < .05) but not by a Jak2 inhibitor, AG-490, suggesting that rhMIF induces ICAM-1 expression in MNs via Src, PI3K, and NFκB. rhMIF induced a 3-fold increase in MN ICAM-1 expression compared with NS. (B) rhMIF-induced ICAM-1 expression was significantly decreased by antisense ODNs of Src, PI3K, and NFκB compared with MNs transfected with sense ODNs of Src, PI3K, and NFκB in 8 to 12 hours (*P < .05). Panel B shows the percentage of inhibition in ICAM-1 expression by antisense ODNs of Src, PI3K, and NFκB compared with corresponding sense ODNs. Data represent the mean of 3 individual experiments (n) ± SEM. *P < .05 was considered significant.

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