Pheophorbide a: A photosensitizer with immunostimulating activities on mouse macrophage RAW 264.7 cells in the absence of irradiation

Pheophorbide a (Pa) has been proposed to be a potential photosensitizer for the photodynamic therapy of human cancer. However, the immunomodulatory effect of Pa, in the absence of irradiation, has not yet been investigated. The present study revealed that Pa possessed immunostimulating effect on a murine macrophages cell line RAW 264.7. Pa could significantly stimulate the growth of RAW 264.7 cells with the maximum effect at 1.0 μM after 24, 48 and 72 h of treatment (all p < 0.05). Besides, intracellular mitogen activated protein kinases (MAPK) including extracellular signal-regulated kinase (ERK) and p38 MAPK were activated by Pa treatment in a dose-dependent manner. The activation of ERK and p38 MAPK was found to be related to the Pa-induced intracellular reactive oxygen species. Furthermore, Pa could significantly induce the release of interleukine-6 and tumour necrosis factor-α, and enhance the phagocytic activity of RAW 264.7 cells (all p < 0.05). The present work is the first report to demonstrate the potential immunomodulatory effect of Pa on macrophages, apart from its well-studied anti-tumour activity.