SP and IL-33 together markedly enhance TNF synthesis and secretion from human mast cells mediated by the interaction of their receptors

Authors: Alexandra Taracanova, Mihail Alevizos, Anna Karagkouni, Zuiy Weng, Errol R. Norwitz, Pio Conti, Susan E. Leeman, Theoharis C. Theoharides - Proceedings of the National Academy of Sciences, PNAS 2017 cited by 128

Significance Inflammatory responses are often characterized by elevated levels of cytokines, but the complex interplay among peptides and cytokines is not often considered. Here, we report that the cytokine IL-33, administered in combination with the proinflammatory peptide substance P (SP), causes a marked increase in tumor necrosis factor synthesis and secretion from cultured human mast cells. These responses are mediated via the activation of the SP receptor NK-1 and the IL-33 receptor ST2 and can be inhibited by the natural flavonoid methoxyluteolin. Our findings reveal interactions that increase the understanding of inflammation and offer new directions for the development of antiinflammatory drugs.