The in vitro Effects of Advanced Glycation End Products on Basophil Functions

Abstract

Background: Basophils are thought to play pivotal roles in the pathogenesis of allergic reactions, but their roles in inflammation associated with systemic abnormalities such as metabolic disorders remain largely unknown. Advanced glycation end products (AGEs) are potentially important substances produced in high-glucose disease conditions. In this in vitro study, we investigated whether the biological functions of human basophils can be influenced by AGEs. Methods: We analyzed the effects of AGEs on various functions and markers of human basophils, including CD11b expression, apoptosis, degranulation, and cytokine production. Results: Flow cytometric analysis indicated that the level of the receptor for AGEs (RAGE) on the surface of freshly isolated basophils was very low but was clearly upregulated by IL-3. Apoptosis of basophils was induced by high concentrations of glycated albumin. Although glycated albumin failed to affect the level of surface CD11b expression or to trigger degranulation or production of IL-4 and IL-13 in basophils, it dose-dependently induced IL-6 and IL-8 secretion. Conclusions: AGEs seem to act on human basophils; they suppress the cells’ longevity but elicit secretion of inflammatory cytokines. Through these biological changes, basophils might play some roles in inflammatory conditions associated with metabolic disorders presenting elevated levels of AGEs.

Modulation of cell proliferation, survival and gene expression by RAGE and TLR signaling in cells of the innate and adaptive immune response: role of p38 MAPK and NF-KB

“…Activation of RAGE is associated with increased cell survival of eosinophils stimulated with S100B, a RAGE ligand, over a period of 48 hours, which is similar to our findings in the same experimental period 5 . The role of RAGE activation in increased cell survival is also suggested by a report of a positive correlation between the expression of RAGE and cell viability in neoplastic pancreatic cells 8 . Inhibition of p38 MAPK did not modulate apoptosis of T lymphocytes and monocytes in the presence and absence of RAGE and TLR4 agonists, and similar findings are reported in literature in T lymphocytes and monocytes 30 .…”

“…However, the experimental period was 5 days, as opposed to 1, 2 and 3 days in our study. Lower concentrations of AGE-BSA (1, 10 and 100 ug/mL) are not capable of inducing apoptosis in human basophils, which was only observed with high concentrations (1,000 ug/mL) at 48 h 8 . Activation of RAGE is associated with increased cell survival of eosinophils stimulated with S100B, a RAGE ligand, over a period of 48 hours, which is similar to our findings in the same experimental period 5 .…”

Effect of high glucose, Porphyromonas gingivalis lipopolysaccharide and advanced glycation end‐products on production of interleukin‐6/‐8 by gingival fibroblasts

“…In animals, it has been shown that dietary AGE-BSA results in elevation of IL-6 in their blood serum (33). AGEs also induced IL-6 and IL-8 secretion from human basophil cells (34) and from osteoarthritis chondrocytes by the activation of nuclear factor-jB (NF-jB) (35). Consistent with these previous reports, we observed that the incubation of HGFs with 200 lg/mL of AGEs (33) could significantly increase their production of IL-6.…”

The false alarm hypothesis: Food allergy is associated with high dietary advanced glycation end-products and proglycating dietary sugars that mimic alarmins

“…RAGE is highly expressed on DCs, macrophages, T lymphocytes, and B cells, as well as mast cells and basophils. 32,[46][47][48][49] AGEs binding to the RAGE receptor activate mast cells and induce exocytosis of histamine and generation of oxidative stress products in a dose-dependent mechanism (within 20 seconds). 49 T-cell activation and proliferation is dependent on RAGE activation, 25 and DCs require RAGE signaling for migration to lymph nodes in response to an antigen.…”