The signalling pathway for BCG-induced interleukin-6 production in human bladder cancer cells

Area of Science:

• Oncology
• Immunology
• Cell Biology

Background:

• Intravesical bacillus Calmette-Guerin (BCG) is a primary treatment for superficial bladder cancer, showing a 60-70% response rate.
• BCG is known to induce cytokine production, such as interleukin-6 (IL-6), in vivo and in vitro, but the underlying signaling pathways remain largely unknown.

Purpose of the Study:

• To investigate the effect of BCG on cyclic adenosine monophosphate (cAMP) production in human bladder cancer cells.
• To elucidate the role of cAMP in regulating IL-6 expression following BCG treatment in the MGH cell line.

Main Methods:

• MGH human bladder cancer cells were exposed to BCG.
• Measurements of IL-6 gene expression and cAMP production were performed.
• The effects of inhibitors (antifibronectin antibody, SQ22536, H7, HA1004) on BCG-induced responses were analyzed.

Main Results:

• BCG exposure led to a time- and dose-dependent increase in both IL-6 gene expression (2.5-3-fold) and cAMP production (8-10-fold) in MGH cells.
• BCG-induced cAMP production was significantly inhibited by antifibronectin antibody and SQ22536.
• Inhibition of cAMP production with SQ22536 markedly reduced IL-6 expression, and cAMP-dependent kinase inhibitors (H7, HA1004) also suppressed BCG-induced IL-6 expression.

Conclusions:

• BCG treatment stimulates cAMP production in human bladder cancer cells.
• The findings suggest that BCG may regulate IL-6 expression, at least partially, through a cAMP-dependent signaling pathway.