Espinal, Alexis and Epperly, Michael W. and Mukherjee, Amitava and Fisher, Renee and Shields, Donna and Wang, Hong and Huq, M. Saiful and Hamade, Diala Fatima and Vlad, Anda M. and Coffman, Lan and Buckanovich, Ronald and Yu, Jian and Leibowitz, Brian J. and van Pijkeren, Jan-Peter and Patel, Ravi B. and Stolz, Donna and Watkins, Simon and Ejaz, Asim and Greenberger, Joel S.
(2022)
Intestinal Radiation Protection and Mitigation by Second-Generation Probiotic Lactobacillus-reuteri Engineered to Deliver Interleukin-22.
International Journal of Molecular Sciences, 23 (10).
p. 5616.
ISSN 1422-0067
Abstract
1) Background: The systemic administration of therapeutic agents to the intestine including cytokines, such as Interleukin-22 (IL-22), is compromised by damage to the microvasculature 24 hrs after total body irradiation (TBI). At that time, there is significant death of intestinal microvascular endothelial cells and destruction of the lamina propria, which limits drug delivery through the circulation, thus reducing the capacity of therapeutics to stabilize the numbers of Lgr5+ intestinal crypt stem cells and their progeny, and improve survival. By its direct action on intestinal stem cells and their villus regeneration capacity, IL-22 is both an ionizing irradiation protector and mitigator. (2) Methods: To improve delivery of IL-22 to the irradiated intestine, we gavaged Lactobacillus-reuteri as a platform for the second-generation probiotic Lactobacillus-reuteri-Interleukin-22 (LR-IL-22). (3) Results: There was effective radiation mitigation by gavage of LR-IL-22 at 24 h after intestinal irradiation. Multiple biomarkers of radiation damage to the intestine, immune system and bone marrow were improved by LR-IL-22 compared to the gavage of control LR or intraperitoneal injection of IL-22 protein. (4) Conclusions: Oral administration of LR-IL-22 is an effective protector and mitigator of intestinal irradiation damage.
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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID |
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Espinal, Alexis | ame96@pitt.edu | ame96 | | Epperly, Michael W. | epperly@pitt.edu | epperly | | Mukherjee, Amitava | amm223@pitt.edu | amm223 | 0000-0001-5603-5147 | Fisher, Renee | rlr45@pitt.edu | rlr45 | | Shields, Donna | shieldsd@pitt.edu | shieldsd | | Wang, Hong | how8@pitt.edu | how8 | | Huq, M. Saiful | msh34@pitt.edu | msh34 | | Hamade, Diala Fatima | | | | Vlad, Anda M. | anvst12@pitt.edu | anvst12 | | Coffman, Lan | lgc14@pitt.edu | lgc14 | | Buckanovich, Ronald | rjb101@pitt.edu | rjb101 | | Yu, Jian | jiy3@pitt.edu | jiy3 | 0000-0002-4021-1000 | Leibowitz, Brian J. | bjl40@pitt.edu | bjl40 | | van Pijkeren, Jan-Peter | | | | Patel, Ravi B. | rbp27@pitt.edu | rbp27 | | Stolz, Donna | donna.stolz@pitt.edu | donna.stolz | | Watkins, Simon | swatkins@pitt.edu | swatkins | | Ejaz, Asim | asa118@pitt.edu | asa118 | | Greenberger, Joel S. | joelg@pitt.edu | joelg | 0000-0003-2271-7566 |
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Centers: |
Other Centers, Institutes, Offices, or Units > Hillman Cancer Center |
Date: |
17 May 2022 |
Date Type: |
Publication |
Journal or Publication Title: |
International Journal of Molecular Sciences |
Volume: |
23 |
Number: |
10 |
Publisher: |
MDPI AG |
Page Range: |
p. 5616 |
DOI or Unique Handle: |
10.3390/ijms23105616 |
Schools and Programs: |
School of Public Health > Biostatistics |
Refereed: |
Yes |
Uncontrolled Keywords: |
ionizing irradiation, whole abdomen irradiation, radioprotection, radiation mitigation, Lactobacillus reuteri-IL-22 |
ISSN: |
1422-0067 |
Official URL: |
http://dx.doi.org/10.3390/ijms23105616 |
Funders: |
National Institute of Allergy and Infectious Diseases |
Article Type: |
Research Article |
Date Deposited: |
06 Jun 2022 15:39 |
Last Modified: |
06 Jun 2022 15:39 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/43058 |
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