Abstract |
The pathogenesis of inflammatory bowel diseases (IBD) is complex, and dysregulated immune responses play a pivotal role in its occurrence and development. Our previous studies indicated that CD30L may participate in monocyte-mediated inflammation in patients with UC through the activation of circulating monocytes. However, it remains unclear how CD30L participates in monocyte-mediated inflammation in IBD by activation of circulating monocytes. In this study, we observed an increase in the expression of CD30L and chemokine receptor type 2 (CCR2) on circulating monocytes and pro-inflammatory monocytes in the colon lamina propria in mice with dextran sulfate sodium salt (DSS)-induced colitis. Moreover, there was a positive correlation between the expression levels of CCR2 and CD30L (r = 0.8817, p = 0.0480) in monocytes. In Cd30l-/- mice with DSS-induced colitis, the percentage and absolute number of circulating monocytes and pro-inflammatory monocytes decreased with the downregulation of CCR2. Stimulation via CD30L by immobilized anti-CD30L mAb suppressed the expression of pNF-κB p65, pIκBα, p65 and CCR2 and up-regulated the expression of IκBα in the sorted pro-inflammatory monocytes in Cd30l-/- mice with DSS-induced colitis. The mRNA levels of Ccr2 in the sorted pro-inflammatory monocytes were significantly down-regulated with the presence of immobilized RM153 and inhibitors of NF-κB (BAY 11-7082) in WT mice with DSS-induced colitis. Our results suggested that CD30L could promote the inflammatory response by inducing the homing and differentiation of monocytes via the chemokine ligand 2 (CCL2)/CCR2 axis and NF-κB signaling pathway in mice with colitis. These findings provide a novel target for monocyte-based immunotherapy against IBD.
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Authors | Chenxue Mei, Fanxiang Meng, Xiao Wang, Siqi Yan, Qianqian Zheng, Xiaoqing Zhang, Wenda Fu, Junxiu Xue, Shengyi Wang, Yan He, Xun Sun, Xuefeng Jiang, Yuanyuan Wang |
Journal | International immunopharmacology
(Int Immunopharmacol)
Vol. 110
Pg. 108934
(Sep 2022)
ISSN: 1878-1705 [Electronic] Netherlands |
PMID | 35834956
(Publication Type: Journal Article)
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Copyright | Copyright © 2022. Published by Elsevier B.V. |
Chemical References |
- CD30 Ligand
- Ccr2 protein, mouse
- Chemokines
- Ki-1 Antigen
- Ligands
- NF-kappa B
- Receptors, CCR2
- Receptors, Chemokine
- Tnfsf8 protein, mouse
- Dextran Sulfate
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Topics |
- Animals
- CD30 Ligand
(metabolism)
- Chemokines
(metabolism)
- Colitis
(metabolism, pathology)
- Dextran Sulfate
- Disease Models, Animal
- Inflammation
(metabolism)
- Inflammatory Bowel Diseases
- Ki-1 Antigen
- Ligands
- Mice
- Mice, Inbred C57BL
- Monocytes
(metabolism)
- NF-kappa B
(metabolism)
- Receptors, CCR2
(genetics, metabolism)
- Receptors, Chemokine
(metabolism)
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