IntroductionIndole-3-carbinol (I3C) is found in cruciferous vegetables and used as a dietary supplement.It is known to act as a ligand for aryl hydrocarbon receptor (AhR).In the current study, we investigated the role of AhR and the ability of I3C to attenuate LPS-induced Acute Respiratory Distress Syndrome (ARDS).
MethodsTo that end, we induced ARDS in wild-type C57BL/6 mice, Ccr2gfp/gfp KI/KO mice (mice deficient in the CCR2 receptor), and LyZcreAhRfl/fl mice (mice deficient in the AhR on myeloid linage cells).Additionally, mice were treated with I3C (65 mg/kg) or vehicle to investigate its efficacy to treat ARDS.ResultsI3C decreased the neutrophils expressing CXCR2, a receptor associated with neutrophil recruitment in the lungs.
In addition, annie brocoli dvd LPS-exposed mice treated with I3C revealed downregulation of CCR2+ monocytes in the lungs and lowered CCL2 (MCP-1) protein levels in serum and bronchoalveolar lavage fluid.Loss of CCR2 on monocytes blocked the recruitment of CXCR2+ neutrophils and decreased the total number of immune cells in the lungs during ARDS.In addition, loss of the AhR on myeloid linage cells ablated I3C-mediated attenuation of CXCR2+ neutrophils and CCR2+ monocytes in the lungs from ARDS animals.
Interestingly, scRNASeq showed that shades eq 07m in macrophage/monocyte cell clusters of LPS-exposed mice, I3C reduced the expression of CXCL2 and CXCL3, which bind to CXCR2 and are involved in neutrophil recruitment to the disease site.DiscussionThese findings suggest that CCR2+ monocytes are involved in the migration and recruitment of CXCR2+ neutrophils during ARDS, and the AhR ligand, I3C, can suppress ARDS through the regulation of immune cell trafficking.