Impact of environmental nitrogen pollution on pollen allergy: A scoping review.

The current rise in the prevalence of allergies to aeroallergens is incompletely understood and attributed to interactions with environmental changes and lifestyle changes. Environmental nitrogen pollution might be a potential driver of this increasing prevalence. While the ecological impact of excessive nitrogen pollution has been widely studied and is relatively well understood, its indirect effect on human allergies is not well documented. Nitrogen pollution can affect the environment in various ways, including air, soil, and water. We aim to provide a literature overview of the nitrogen-driven impact on plant communities, plant productivity, and pollen properties and how they lead to changes in allergy burden. We included original articles investigating the associations between nitrogen pollution, pollen, and allergy, published in international peer-reviewed journals between 2001 and 2022. Our scoping review found that the majority of studies focus on atmospheric nitrogen pollution and its impact on pollen and pollen allergens, causing allergy symptoms. These studies often examine the impact of multiple atmospheric pollutants and not just nitrogen, making it difficult to determine the specific impact of nitrogen pollution. There is some evidence that atmospheric nitrogen pollution affects pollen allergy by increasing atmospheric pollen levels, altering pollen structure, altering allergen structure and release, and causing increased allergenic reactivity. Limited research has been conducted on the impact of soil and aqueous nitrogen pollution on pollen allergenic reactivity. Further research is needed to fill the current knowledge gap about the impact of nitrogen pollution on pollen and their related allergic disease burden.

The Chemokine-Based Peptide, CXCL9(74-103), Inhibits Angiogenesis by Blocking Heparan Sulfate Proteoglycan-Mediated Signaling of Multiple Endothelial Growth Factors.

Growth factors such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and epidermal growth factor (EGF) are important angiogenesis-mediating factors. They exert their effects not only through their respective receptor tyrosine kinases (RTKs), but they also require molecular pairing with heparan sulfate proteoglycans (HSPGs). Angiogenic growth factors and their signaling pathways are commonly targeted in current anti-angiogenic cancer therapies but have unfortunately insufficient impact on patient survival. Considering their obvious role in pathological angiogenesis, HS-targeting drugs have become an appealing new strategy. Therefore, we aimed to reduce angiogenesis through interference with growth factor-HS binding and downstream signaling using a CXCL9-derived peptide with a high affinity for glycosaminoglycans (GAGs), CXCL9(74-103). We showed that CXCL9(74-103) reduced EGF-, VEGF165- and FGF-2-mediated angiogenic processes in vitro, such as endothelial cell proliferation, chemotaxis, adhesion and sprouting, without exerting cell toxicity. CXCL9(74-103) interfered with growth factor signaling in diverse ways, e.g., by diminishing VEGF165 binding to HS and by direct association with FGF-2. The dependency of CXCL9(74-103) on HS for binding to HMVECs and for exerting its anti-angiogenic activity was also demonstrated. In vivo, CXCL9(74-103) attenuated neovascularization in the Matrigel plug assay, the corneal cauterization assay and in MDA-MB-231 breast cancer xenografts. Additionally, CXCL9(74-103) reduced vascular leakage in the retina of diabetic rats. In contrast, CXCL9(86-103), a peptide with low GAG affinity, showed no overall anti-angiogenic activity. Altogether, our results indicate that CXCL9(74-103) reduces angiogenesis by interfering with multiple HS-dependent growth factor signaling pathways.