PM2.5 Exposure Induced Autophagy Activation via the ROS/AMPK/mTOR/ULK1 Signaling Axis in Macrophages

Abstract

RATIONALE: Previously we have shown increased A Proliferation-Inducing Ligand (APRIL) and B-cell Activation Factor (BAFF) concentrations in colostrum are associated with protection against allergic disease. APRIL and BAFF, together with IL-10 and TGFb, are known to induce T-cell independent (TI) IgA class switch recombination (CSR) in Bcells. Our goal was to assess whether human milk containing these cytokines, would induce CSR in cord blood B-cells. METHODS: B-cells were isolated from cord blood mononuclear cells (CBMCs) by IgD selection and were then cultured for 3-7 days with treatments: culture medium containing human milk or combination of APRIL and TGFb1. Cells were then analyzed by flow cytometry for detection of IgA1 and IgA2 positive B-cells. RESULTS: B-cell CSR assay protocols were established. IgA B-cells were readily detectable following the assay protocol, using APRIL and TGFb1 stimulation as positive controls. Using the protocol we noted a robust IgA class switching following stimulation using sterile filtered human milk. CONCLUSIONS: We have established a protocol that will allow more detailed assessment of several cytokines in human milk class switch recombination. Future experiments will characterize in detail which cytokines affect CSR and IgA production to elicit the role of human milk in protection against onset of allergic disease.

Micro- and Nanosized Substances Cause Different Autophagy-Related Responses

“…Metal nanomaterials have the potential to induce dermal and respiratory allergies [ 166 ]. PM2.5 induces autophagy markers, such as Beclin 1, ULK-1, and LC3 [ 167 , 168 ], and results in developmental toxicity in zebrafish embryos [ 169 ], autophagy-mediated cell death in human bronchial epithelium cells [ 170 ], and cardiac dysfunction [ 171 ]. PM2.5 may represent a significant risk factor for the development of Alzheimer’s disease [ 172 ].…”