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Cannabinoid-2 receptor signaling in vesicant induced lung injury

Award Number: R21ES033007
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/18/2021
PERIOD OF PERFORMANCE END DATE: 06/30/2024

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Cannabinoid-2 receptor signaling in vesicant induced lung injury - Sulfur mustard (SM), a vesicant that is one of the most lethal chemical warfare agents, remains as a great threat in modern times. Exposure to SM and its mono-functional analog 2-chloroethyl ethyl sulfide (CEES) induces deleterious effects on the lung. Oxidative stress and uncontrolled inflammation are considered as the major mechanisms of SM toxicity on the lung. Currently, there are no effective medical countermeasures to mitigate the vesicant induced lung damage. Therefore, it is essential to expand our understanding of the molecular mechanisms and to identify effective measures, including pharmacological interventions, to alleviate the inflammation and oxidative stress induced by SM. Cannabinoid-2 receptors (CB2R), expressed mainly in the immune cells, have shown promising anti-inflammatory and anti-injury potential without any adverse psychotic effects. Our preliminary findings indicated a significant reduction of CEES- induced acute lung injury and immune cell infiltration by pharmacological activation of CB2R, while the genetic deletion of CB2R worsened the lung injury. Moreover, CB2R ligands show marked functional selectivity, suggesting CB2R can be a good target for developing counter measures to CEES. Given these promising indications, this project aims to further investigate how CB2R activation attenuates CEES-induced acute lung injury, using pharmacological activation and genetic deletion approach in the following specific aims: 1) To determine the extent to which CB2R regulates the CEES-induced acute lung injury, inflammatory response, and oxidative stress. 2) To delineate the mechanism of the protective role of CB2R in CEES-induced lung injury, inflammatory response, and oxidative stress. These efforts will reveal a novel mechanism of endocannabinoid signaling through CB2R in CEES-induced lung injury and would assist in translational strategies for the development of therapeutic agent against vesicant-induced lung damage.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = -$8,011 )
2025	2022	OLD DOMINION UNIVERSITY	735 FAIRFAX AVE STE 909	NORFOLK	VA	23507	NORFOLK CITY	USA	Environmental Health	000	2	1/3/2025	NON-COMPETING CONTINUATION	-$8,011
														Subtotal = -$8,011

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	EASTERN VIRGINIA MEDICAL SCHOOL	735 FAIRFAX AVE STE 909C	NORFOLK	VA	23507	NORFOLK CITY	USA	Environmental Health	000	2	6/12/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $191,283 )
2022	2022	EASTERN VIRGINIA MEDICAL SCHOOL	735 FAIRFAX AVE STE 909C	NORFOLK	VA	23507	NORFOLK CITY	USA	Environmental Health	000	2	8/10/2022	NON-COMPETING CONTINUATION	$191,283
														Subtotal = $191,283

Issue Date FY: 2021 ( Subtotal = $241,315 )
2021	2021	EASTERN VIRGINIA MEDICAL SCHOOL	358 MOWBRAY ARCH STE 305	NORFOLK	VA	23507	NORFOLK CITY	USA	Environmental Health	000	1	8/17/2021	NEW	$241,315
														Subtotal = $241,315

Grand Total All Awards = $424,587

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Cannabinoid-2 receptor signaling in vesicant induced lung injury

Award Number: R21ES033007

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/18/2021

PERIOD OF PERFORMANCE END DATE: 06/30/2024

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