Date of Completion
2015
Thesis Type
College of Arts and Science Honors
Department
Biology
First Advisor
Vikas Anathy
Second Advisor
Christopher Landry
Keywords
mitochondria, ER, asthma, house dust mite, ER-mito interactions, mitochondrial fission
Abstract
Rationale: Airway epithelial cells (AECs) are critical regulators of inflammatory, immune and injury responses to allergens that contribute to asthma pathogenesis. The response of AECs to allergens requires an integrated-complex, extracellular receptors and intracellular organelle interaction to achieve secretion of pro-inflammatory cytokines and chemokines. Endoplasmic reticulum (ER) and mitochondria interactions have previously been shown to induce mitochondrial fission. Mitochondrial fission may be a key parameter allergen induced airway inflammation in asthma. However, ER-mitochondria interactions, mitochondrial fission, and subsequent production and secretion of cytokines and chemokines in response to House Dust Mite (HDM) are not well understood.
Objective: Here we will assess the ability of HDM to induce ER-mitochondrial interactions and subsequent mitochondrial fission in human bronchiolar epithelial (HBE) cells. We will also investigate the impact on cytokine production downstream of mitochondrial fission in HBE cells treated with HDM.
Methods: ER-mitochondrial interactions were quantified using confocal and epifluorescence microscopy. Cytokine/chemokine profiles were determined by enzyme linked immunosorbant assay (ELISA) using HBE cells treated with HDM.
Measurements and Main Results: Using epifluorescence and confocal microscopy we show that ER-mitochondrial contacts are increased in response to HDM treatment, as well as HDM-induced mitochondrial fission increased in HBE cells. Inhibition of DRP1, a protein essential for mitochondrial fission, decreases HDM induced ER-mitochondrial interaction. In addition, HDM-induced pro-inflammatory cytokines were decreased in HBE cells where mitochondrial fission is inhibited.
Conclusion: HDM induces ER-Mitochondrial interactions that promote mitochondrial fission and subsequent production of pro-inflammatory cytokines.
Recommended Citation
Cahoon, Jonathon M. and Anathy, Vikas, "Endoplasmic Reticulum - Mitochondrial Interactions in House Dust Mite Induced Inflammation" (2015). UVM College of Arts and Sciences College Honors Theses. 12.
https://scholarworks.uvm.edu/castheses/12