IL-33 augments substance P–induced VEGF secretion from human mast cells and is increased in psoriatic skin
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- 16 February 2010
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 107 (9), 4448-4453
- https://doi.org/10.1073/pnas.1000803107
Abstract
The peptide substance P (SP) has been implicated in inflammatory conditions, such as psoriasis, where mast cells and VEGF are increased. A relationship between SP and VEGF has not been well studied, nor has any interaction with the proinflammatory cytokines, especially IL-33. Here we report that SP (0.1–10 μM) induces gene expression and secretion of VEGF from human LAD2 mast cells and human umbilical core blood-derived cultured mast cells (hCBMCs). This effect is significantly increased by coadministration of IL-33 (5–100 ng/mL) in both cell types. The effect of SP on VEGF release is inhibited by treatment with the NK-1 receptor antagonist 733,060. SP rapidly increases cytosolic calcium, and so does IL-33 to a smaller extent; the addition of IL-33 augments the calcium increase. SP-induced VEGF production involves calcium-dependent PKC isoforms, as well as the ERK and JNK MAPKs. Gene expression of IL-33 and histidine decarboxylase (HDC), an indicator of mast cell presence/activation, is significantly increased in affected and unaffected (at least 15 cm away from the lesion) psoriatic skin, as compared with normal control skin. Immunohistochemistry indicates that IL-33 is associated with endothelial cells in both the unaffected and affected sites, but is stronger and also associated with immune cells in the affected site. These results imply that functional interactions among SP, IL-33, and mast cells leading to VEGF release contribute to inflammatory conditions, such as the psoriasis, a nonallergic hyperproliferative skin inflammatory disorder with a neurogenic component.Keywords
This publication has 83 references indexed in Scilit:
- PsoriasisNew England Journal of Medicine, 2009
- The cytokine interleukin-33 mediates anaphylactic shockProceedings of the National Academy of Sciences of the United States of America, 2009
- Angiogenesis drives psoriasis pathogenesisInternational Journal of Experimental Pathology, 2009
- The IL-1-Like Cytokine IL-33 Is Constitutively Expressed in the Nucleus of Endothelial Cells and Epithelial Cells In Vivo: A Novel 'Alarmin'?PLOS ONE, 2008
- IL-33 exacerbates antigen-induced arthritis by activating mast cellsProceedings of the National Academy of Sciences of the United States of America, 2008
- PsoriasisNew England Journal of Medicine, 2005
- Presence of NK1receptors on a mucosal-like mast cell line, RBL-2H3 cellsCanadian Journal of Physiology and Pharmacology, 1998
- QUANTITATIVE HISTOCHEMICAL ANALYSIS OF MAST CELLS AND SENSORY NERVES IN PSORIATIC SKINThe Journal of Pathology, 1996
- Neuropeptides and general neuronal marker in psoriasis an immunohistochemical studyClinical and Experimental Dermatology, 1995
- Stress, symmetry, and psoriasis: Possible role of neuropeptidesJournal of the American Academy of Dermatology, 1986