Background: Platelet-derived growth factor (PDGF) is a potent stimulator of growth and motility of vascular smooth muscle cells (VSMCs). Abnormalities of PDGF/PDGF receptor (PDGFR) are thought to contribute to vascular diseases and malignancy. We previously showed that a carotenoid, lycopene, can directly bind to PDGF and affect its related functions in VSMCs. In this study we examined the effect of the other naturally occurring carotenoid, lutein, on PDGF signaling and migration in VSMCs. Methods: Western blotting was performed to examine PDGF and H₂O₂ signaling. Flowcytometry was used to determine PDGF binding to VSMCs. Fluorescence microscopy was performed to examine intracellular ROS production. Modified Boyden chamber system (Transwell apparatus) was used for migration assay. Results: Lutein reduced PDGF signaling, including phosphorylation of PDGFR-β and its downstream protein kinases/enzymes such as phospholipase C-γ, Akt, and mitogen-activated protein kinases (MAPKs). Although lutein possesses a similar structure to lycopene, it was striking that lutein inhibited PDGF signaling through a different way from lycopene in VSMCs. Unlike lycopene, lutein not only interacted with (bound to) PDGF but also interfered with cellular components. This was evidenced that preincubation of PDGF with lutein and treatment of VSMCs with lutein followed by removing of lutein compromised PDGF-induced signaling. Lutein reduced PDGF-induced intracellular reactive oxygen species (ROS) production and attenuated ROS- (H₂O₂-) induced ERK1/2 and p38 MAPK activation. A further analysis indicated lutein could inhibit a higher concentration of H₂O₂-induced PDGFR signaling, which is known to act through an oxidative inhibition of protein tyrosine phosphatase. Finally, we showed that lutein functionally inhibited PDGF-induced VSMC migration, whereas its stereo-isomer zeaxanthin did not, revealing a special action of lutein on VSMCs. Conclusions: Our study reveals a differential action mechanism of lutein from other reported caroteinoids and suggests a possible beneficial effect of lutein but not zeaxanthin on prevention of vascular diseases.

Interleukin-33 (IL-33) could play an important role in the pathogenesis of angiostrongylosis. However, the role of IL-33/ST2 pathway in this parasitic infection is uncertain. C57BL/six mice were each infected with 35 Angiostrongylus cantonensis larvae. One group of mice received an intraperitoneal injection of anti-ST2 monoclonal antibody (mAb; 50 μg) 3 days postinfection and subsequent booster shots of the same dose at 5-day intervals. Blood samples from each group were collected every week for assays. The level of IL-5 significantly decreased in the mAb-treated group, and the infiltration of eosinophils in the meninges was also significantly reduced. The IL-33/ST2 axis may play a crucial role in the pathogenesis of angiostrongylosis and the results of this study could be useful for the development of strategies to reduce the neurological damage caused by this parasitic infection.

The purpose of this study is to clarify the role of IL-33 in the immune response to angiostrongyliasis, especially in terms of antibody production and isotype switching. In our experiment, C57BL/6 mice were each infected with 35 infectious larvae and were divided into groups that received an intraperitoneal injection of IL-33, anti-IL-33 monoclonal antibody (mAb), or anti-ST2 mAb 3 days post-infection (dpi) and were subsequently administered booster shots at 5-day intervals with the same dose. Serum samples from each group were collected weekly for ELISA assays. The levels of total IgG, IgG1, and IgG3 were significantly increased in A. cantonensis-infected mice that were treated with IL-33, and the levels decreased significantly in infected groups treated with anti-IL-33 or anti-ST2 mAb. These results suggest that IL-33 may play a critical role in the pathogenesis of human angiostrongyliasis and could be useful for understanding protective immunity against this parasitic infection.

This study aimed to investigate the role of interleukin (IL)‐25 in the pathogenesis of angiostrongylosis. We used ICR mice as non‐permissive hosts, divided them into groups and experimentally infected them with infective larvae of the Angiostrongylus cantonensis . Two groups of infected mice were injected intraperitoneally with either mouse IL‐25 or an anti‐IL‐25 monoclonal antibody (mAb) at 3 days post‐infection (dpi), followed by booster injections at the same dose every 5 days. Serum samples and brain tissues were collected weekly from each group for immunological and pathological examinations. The IL‐25‐treated group exhibited significant increases in eosinophil percentages and levels of immunoglobulin E (IgE), as well as in the levels of IL‐5 and IL‐13. The severity of eosinophilic meningitis was exacerbated in the IL‐25‐treated group 21 dpi. These results suggest that IL‐25 may enhance eosinophil‐associated inflammation in mice infected with A. cantonensis .