Figure 10.

Anti-dsDNA antibodies induce IL-6 secretion in HMC. (A) IL-6 transcript in HMC incubated with SFM, control IgG, or six different human polyclonal anti-dsDNA antibodies as assessed by real-time PCR. *P < 0.01 for anti-dsDNA Ab versus SFM or control IgG for same time point. (B) IL-6 secretion in HMC incubated with SFM, control IgG, and anti-dsDNA antibodies (encompasses anti-dsDNA antibodies that localize to the cytoplasm [gray circle] and nucleus [black circle]). The horizontal line in each group represents the mean IL-6 secretion. **P < 0.001 for SFM or control IgG versus anti-DNA Ab. (C) IL-6 secretion in HMC incubated with SFM (white bars), control IgG (gray bars), and anti-dsDNA antibodies (black bars) in the presence or absence of specific inhibitors to PKC, ERK, p38 MAPK, JNK, and PI3K. *P < 0.01 for anti-dsDNA antibody versus SFM or control IgG for the same group; #P < 0.05 or §P < 0.01 for with versus without inhibitor. (D) IL-6 secretion from HMC incubated with anti-dsDNA antibodies with (black bars) or without (white bars) prior crosslinking of cell surface annexin II or annexin II antibody (gray bars). Crosslinking of cell surface annexin II with annexin II Ab, but not control Ab (marked white bars), enhanced the subsequent induction of IL-6 by anti-dsDNA antibodies. The data are presented as the means ± SD. **P < 0.001, anti-dsDNA Ab alone, annexin II Ab alone, or control Ab versus cross-linking with annexin II Ab. The horizontal axis denotes the time of incubation with anti-dsDNA antibodies.