New insights into DEHP-induced inflammatory injury in chicken spleen: ROS/TLR4/MyD88 pathway and apoptosis/necroptosis-M1 polarization crosstalk

The environmental endocrine disruptor di(2-ethylhexyl) phthalate (DEHP) is a plasticiser used in large quantities in plastics and is hazardous to the health of humans and various animals. DEHP can be immunotoxic to the spleen through oxidative stress. Still, the role of splenic macrophage polarizati...

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Main Authors: Yue Xu, Xiandan Zhang, Guangxing Li, Rong Guo, Hong Zhang, Bolin Zhao, Xiaoyu Zhao, Kaiting Chen, Xiaodan Huang
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Poultry Science
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Online Access:http://www.sciencedirect.com/science/article/pii/S003257912500313X
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author Yue Xu
Xiandan Zhang
Guangxing Li
Rong Guo
Hong Zhang
Bolin Zhao
Xiaoyu Zhao
Kaiting Chen
Xiaodan Huang
author_facet Yue Xu
Xiandan Zhang
Guangxing Li
Rong Guo
Hong Zhang
Bolin Zhao
Xiaoyu Zhao
Kaiting Chen
Xiaodan Huang
author_sort Yue Xu
collection DOAJ
description The environmental endocrine disruptor di(2-ethylhexyl) phthalate (DEHP) is a plasticiser used in large quantities in plastics and is hazardous to the health of humans and various animals. DEHP can be immunotoxic to the spleen through oxidative stress. Still, the role of splenic macrophage polarization in lymphocyte apoptosis and necroptosis, whether they interact with each other, and the mechanism of the effect on splenic inflammatory injury are unknown. In this study, based on the construction of a time-and dose-dependent model of DEHP-exposed chicken spleen, chicken lymphoma cell (MSB-1) and chicken macrophage (HD11) models were established to investigate the mechanism of apoptosis/necroptosis-M1 polarization crosstalk in DEHP-induced toxicity in chicken spleen injury. The results showed that DEHP exposure activated the ROS/TLR4/MyD88 pathway, up-regulated the expression of chemokines, induced macrophage M1 polarization, caused apoptosis and necroptosis in lymphocytes and inflicted inflammatory damage to the spleen, however, these effects could be alleviated by NAC. DEHP exposure of the HD11/MSB-1 cell co-culture system showed that M1 polarization promoted apoptosis and necroptosis and vice versa. In conclusion, DEHP exposure is involved in mediating the crosstalk between apoptosis/necroptosis and M1 polarization through the activation of the ROS/TLR4/MyD88 pathway, which in turn exacerbates inflammatory injury in the chicken spleen.
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spelling doaj-art-e49ce6548533403a8ff3e1cc69ef13b92025-08-20T03:07:50ZengElsevierPoultry Science0032-57912025-06-01104610507410.1016/j.psj.2025.105074New insights into DEHP-induced inflammatory injury in chicken spleen: ROS/TLR4/MyD88 pathway and apoptosis/necroptosis-M1 polarization crosstalkYue Xu0Xiandan Zhang1Guangxing Li2Rong Guo3Hong Zhang4Bolin Zhao5Xiaoyu Zhao6Kaiting Chen7Xiaodan Huang8College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR ChinaShandong Vocational Animal Science and Veterinary College, PR ChinaLiaoning Petmate Biotechnology Co, PR ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China; Corresponding author. Xiaodan Huang, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China.The environmental endocrine disruptor di(2-ethylhexyl) phthalate (DEHP) is a plasticiser used in large quantities in plastics and is hazardous to the health of humans and various animals. DEHP can be immunotoxic to the spleen through oxidative stress. Still, the role of splenic macrophage polarization in lymphocyte apoptosis and necroptosis, whether they interact with each other, and the mechanism of the effect on splenic inflammatory injury are unknown. In this study, based on the construction of a time-and dose-dependent model of DEHP-exposed chicken spleen, chicken lymphoma cell (MSB-1) and chicken macrophage (HD11) models were established to investigate the mechanism of apoptosis/necroptosis-M1 polarization crosstalk in DEHP-induced toxicity in chicken spleen injury. The results showed that DEHP exposure activated the ROS/TLR4/MyD88 pathway, up-regulated the expression of chemokines, induced macrophage M1 polarization, caused apoptosis and necroptosis in lymphocytes and inflicted inflammatory damage to the spleen, however, these effects could be alleviated by NAC. DEHP exposure of the HD11/MSB-1 cell co-culture system showed that M1 polarization promoted apoptosis and necroptosis and vice versa. In conclusion, DEHP exposure is involved in mediating the crosstalk between apoptosis/necroptosis and M1 polarization through the activation of the ROS/TLR4/MyD88 pathway, which in turn exacerbates inflammatory injury in the chicken spleen.http://www.sciencedirect.com/science/article/pii/S003257912500313XDi-(2-ethylhexyl) phthalateSpleen inflammationROS/TLR4/MyD88 pathwayApoptosis/necroptosis-M1 polarization crosstalkChicken
spellingShingle Yue Xu
Xiandan Zhang
Guangxing Li
Rong Guo
Hong Zhang
Bolin Zhao
Xiaoyu Zhao
Kaiting Chen
Xiaodan Huang
New insights into DEHP-induced inflammatory injury in chicken spleen: ROS/TLR4/MyD88 pathway and apoptosis/necroptosis-M1 polarization crosstalk
Poultry Science
Di-(2-ethylhexyl) phthalate
Spleen inflammation
ROS/TLR4/MyD88 pathway
Apoptosis/necroptosis-M1 polarization crosstalk
Chicken
title New insights into DEHP-induced inflammatory injury in chicken spleen: ROS/TLR4/MyD88 pathway and apoptosis/necroptosis-M1 polarization crosstalk
title_full New insights into DEHP-induced inflammatory injury in chicken spleen: ROS/TLR4/MyD88 pathway and apoptosis/necroptosis-M1 polarization crosstalk
title_fullStr New insights into DEHP-induced inflammatory injury in chicken spleen: ROS/TLR4/MyD88 pathway and apoptosis/necroptosis-M1 polarization crosstalk
title_full_unstemmed New insights into DEHP-induced inflammatory injury in chicken spleen: ROS/TLR4/MyD88 pathway and apoptosis/necroptosis-M1 polarization crosstalk
title_short New insights into DEHP-induced inflammatory injury in chicken spleen: ROS/TLR4/MyD88 pathway and apoptosis/necroptosis-M1 polarization crosstalk
title_sort new insights into dehp induced inflammatory injury in chicken spleen ros tlr4 myd88 pathway and apoptosis necroptosis m1 polarization crosstalk
topic Di-(2-ethylhexyl) phthalate
Spleen inflammation
ROS/TLR4/MyD88 pathway
Apoptosis/necroptosis-M1 polarization crosstalk
Chicken
url http://www.sciencedirect.com/science/article/pii/S003257912500313X
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