Protein Disulfide Isomerases Regulate IgE-Mediated Mast Cell Responses and Their Inhibition Confers Protective Effects During Food Allergy.
| Autor: | Krajewski D; Department of Pharmaceutical and Administrative Sciences, College of Pharmacy and Health Sciences, Western New England University, Springfield, MA, United States., Polukort SH; Department of Pharmaceutical and Administrative Sciences, College of Pharmacy and Health Sciences, Western New England University, Springfield, MA, United States., Gelzinis J; Department of Pharmaceutical and Administrative Sciences, College of Pharmacy and Health Sciences, Western New England University, Springfield, MA, United States., Rovatti J; Department of Pharmaceutical and Administrative Sciences, College of Pharmacy and Health Sciences, Western New England University, Springfield, MA, United States., Kaczenski E; Department of Pharmaceutical and Administrative Sciences, College of Pharmacy and Health Sciences, Western New England University, Springfield, MA, United States., Galinski C; Department of Pharmaceutical and Administrative Sciences, College of Pharmacy and Health Sciences, Western New England University, Springfield, MA, United States., Pantos M; Department of Pharmaceutical and Administrative Sciences, College of Pharmacy and Health Sciences, Western New England University, Springfield, MA, United States., Shah NN; Pioneer Valley Life Sciences Institute, Baystate Medical Center, Springfield, MA, United States.; Department of Veterinary and Animal Sciences, University of Massachusetts at Amherst, Amherst, MA, United States., Schneider SS; Pioneer Valley Life Sciences Institute, Baystate Medical Center, Springfield, MA, United States.; Department of Veterinary and Animal Sciences, University of Massachusetts at Amherst, Amherst, MA, United States., Kennedy DR; Department of Pharmaceutical and Administrative Sciences, College of Pharmacy and Health Sciences, Western New England University, Springfield, MA, United States., Mathias CB; Department of Pharmaceutical and Administrative Sciences, College of Pharmacy and Health Sciences, Western New England University, Springfield, MA, United States.; Department of Veterinary and Animal Sciences, University of Massachusetts at Amherst, Amherst, MA, United States. |
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| Jazyk: | angličtina |
| Zdroj: | Frontiers in immunology [Front Immunol] 2020 Dec 22; Vol. 11, pp. 606837. Date of Electronic Publication: 2020 Dec 22 (Print Publication: 2020). |
| DOI: | 10.3389/fimmu.2020.606837 |
| Abstrakt: | The thiol isomerase, protein disulfide isomerase (PDI), plays important intracellular roles during protein folding, maintaining cellular function and viability. Recent studies suggest novel roles for extracellular cell surface PDI in enhancing cellular activation and promoting their function. Moreover, a number of food-derived substances have been shown to regulate cellular PDI activity and alter disease progression. We hypothesized that PDI may have similar roles during mast cell-mediated allergic responses and examined its effects on IgE-induced mast cell activity during cell culture and food allergy. Mast cells were activated via IgE and antigen and the effects of PDI inhibition on mast cell activation were assessed. The effects of PDI blockade in vivo were examined by treating mice with the irreversible PDI inhibitor, PACMA-31, in an ovalbumin-induced model of food allergy. The role of dietary PDI modulators was investigated using various dietary compounds including curcumin and quercetin-3-rutinoside (rutin). PDI expression was observed on resting mast cell surfaces, intracellularly, and in the intestines of allergic mice. Furthermore, enhanced secretion of extracellular PDI was observed on mast cell membranes during IgE and antigen activation. Insulin turbidimetric assays demonstrated that curcumin is a potent PDI inhibitor and pre-treatment of mast cells with curcumin or established PDI inhibitors such as bacitracin, rutin or PACMA-31, resulted in the suppression of IgE-mediated activation and the secretion of various cytokines. This was accompanied by decreased mast cell proliferation, FcεRI expression, and mast cell degranulation. Similarly, treatment of allergic BALB/c mice with PACMA-31 attenuated the development of food allergy resulting in decreased allergic diarrhea, mast cell activation, and fewer intestinal mast cells. The production of T Competing Interests: CBM and DRK are authors on a patent application submitted by Western New England University regarding the role of thiol isomerases in mast cell activation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2020 Krajewski, Polukort, Gelzinis, Rovatti, Kaczenski, Galinski, Pantos, Shah, Schneider, Kennedy and Mathias.) |
| Databáze: | MEDLINE |
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