CD30L is involved in the regulation of the inflammatory response through inducing homing and differentiation of monocytes via CCL2/CCR2 axis and NF-κB pathway in mice with colitis.
Int Immunopharmacol
; 110: 108934, 2022 Sep.
Article
in En
| MEDLINE
| ID: mdl-35834956
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Monocytes
/
Inflammatory Bowel Diseases
/
Colitis
/
CD30 Ligand
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Int Immunopharmacol
Journal subject:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Year:
2022
Document type:
Article