A new study published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) indicates that substance P (SP) stimulates human mast cells to secrete vascular endothelial growth factor (VEGF) and that this action is augmented by interleukin (IL)-33.
Substance P-positive nerve ﬁbers are denser in psoriatic lesions and have an increased number of mast cell contacts as compared with normal skin.
In correlation, SP-positive nerve ﬁbers and mast cell contacts are also increased by acute stress in mice, and psoriasis is known to worsen with acute stress. Psoriatic plaques also contain increased levels of VEGF compared with normal skin, and VEGF is a major proangiogenic factor involved in many inﬂammatory diseases.
In the PNAS study Theoharides et al. report that IL-33, the newest inﬂammatory member of the IL-1 cytokine family, augments the SP-induced VEGF mRNA expression and VEGF protein secretion in both leukemic and normal human mast cells, but cannot induce VEGF secretion without SP presence.
The authors conclude that the interactions among SP, IL-33, and mast cells may be important in inﬂammatory diseases where there is excessive angiogenesis, such as psoriasis. In this respect, they also discuss that the ability of IL-33 to augment the effect of SP on inducing mast cell release of VEGF is of particular interest, as angiogenesis is at the core of psoriasis pathogenesis.
Thus, SP, IL-33 and mast cells may also represent novel therapeutic targets in this condition.