Dynamic changes of peritoneal macrophages and subpopulations during ulcerative colitis to metastasis of colorectal carcinoma in a mouse model.

Abstract

OBJECTIVE AND DESIGN:

Patients with ulcerative colitis have increased risk of colorectal carcinoma, but little is known about how peritoneal macrophages are involved in ulcerative colitis-associated carcinogenesis. We investigated the alteration of peritoneal macrophages and M1/M2 subpopulations during ulcerative colitis-associated carcinogenesis.

MATERIALS AND METHODS:

Expression and functional changes in peritoneal macrophages and M1/M2 subpopulations were investigated by histopathology, flow cytometry, immunofluorescence, cytokines expression by ELISA and QRT-PCR in an azoxymethane (AOM)- and dextran sodium sulfate (DSS)-induced chemical colitis-associated carcinoma mouse model using male Crj:CD-1 (ICR) mice.

RESULTS:

Striking evidence observed in histopathology, flow cytometry, cytokine detection, and gene expression analysis all revealed that inflammation-associated cytokines (IL-1β, IL-10, IL-12, IL-6, TNF-α) and migration/invasion-associated factors (G-CSF, GM-CSF, CXCR4, VEGF, TGF-β, ICAM-1) induced by peritoneal M2 macrophages increased significantly during the progression from inflammatory hyperplasia to carcinoma and metastasis. Similar functional changes occurred during peritoneal metastasis in M1 macrophages without changed polarization.

CONCLUSIONS:

These results suggested that peritoneal M2 macrophages played a critical role in ulcerative colitis-associated carcinogenesis, including unbalanced pro-inflammatory and anti-inflammatory axis and enhanced expression of migration/invasion-associated factors. Furthermore, functional changes of M1 macrophages occurred without changed polarization during carcinogenesis and metastasis.

• Authors: Wei Wang, Xiayu Li, Danwei Zheng, Decai Zhang, Shuo Huang, Xuemei Zhang, Feiyan Ai, Xiaoyan Wang, Jian Ma, Wei Xiong, Yanhong Zhou, Guiyuan Li, Shourong Shen
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 62 Issue 7 Pg. 669-80 (Jul 2013) ISSN: 1420-908X [Electronic] Switzerland
• PMID: 23625042 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CXCR4 protein, mouse
• Cytokines
• Icam1 protein, mouse
• Receptors, CXCR4
• Transforming Growth Factor beta
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, mouse
• Intercellular Adhesion Molecule-1
• Granulocyte Colony-Stimulating Factor
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Animals
• Colitis, Ulcerative (genetics, immunology)
• Colorectal Neoplasms (genetics, immunology, pathology)
• Cytokines (genetics, immunology)
• Disease Models, Animal
• Granulocyte Colony-Stimulating Factor (genetics)
• Granulocyte-Macrophage Colony-Stimulating Factor (genetics)
• Intercellular Adhesion Molecule-1 (genetics)
• Macrophages, Peritoneal (cytology, immunology)
• Male
• Mice
• Mice, Inbred ICR
• Peritoneal Neoplasms (genetics, immunology, secondary)
• Receptors, CXCR4 (genetics)
• Transforming Growth Factor beta (genetics)
• Vascular Endothelial Growth Factor A (genetics)