Impact of tumor-derived CCL2 on T cell effector function

Vitiello, Peter F.; Shainheit, Mara G.; Allison, E.; Adler, Evan; Kurt, Robert A.

doi:10.1016/j.imlet.2003.12.009

Cited by 34 publications

(24 citation statements)

References 21 publications

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“…The observation that live P. gingivalis is a weak inducer of RANTES, MCP-1, and IFN-␥ may lead to relatively small inflammatory infiltrate and less intensive antigen-specific immune responses (16,47). These reduced immune responses can result in an exaggerated growth of previously constrained subgingival bacteria in the early infection stages.…”

Section: Vol 73 2005 Cytokine Profiling Of Macrophages 939mentioning

confidence: 99%

Cytokine Profiling of Macrophages Exposed toPorphyromonas gingivalis, Its Lipopolysaccharide, or Its FimA Protein

et al. 2005

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To characterize the roles of Porphyromonas gingivalis and its components in the disease processes, we investigated the cytokine profile induced by live P. gingivalis, its lipopolysaccharides (LPS), and its major fimbrial protein, fimbrillin (FimA). Using cytokine antibody arrays, we found that P. gingivalis LPS and FimA induced a similar profile of cytokine expression when exposed to mouse peritoneal macrophages but that this profile differed significantly in response to live P. gingivalis. In vitro, mouse peritoneal macrophages were stimulated to produce interleukin-6 (IL-6), granulocyte colony-stimulating factor, and lymphotactin by live P. gingivalis, but not by P. gingivalis LPS or FimA, while RANTES, gamma interferon, IL-17, vascular cell adhesion molecule 1 (VCAM-1), and vascular endothelial growth factor were induced by P. gingivalis LPS or FimA, but not by live P. gingivalis. In vivo, IL-6 mRNA was strongly induced only by live P. gingivalis while monocyte chemoattractant protein 1 mRNA was strongly induced only by P. gingivalis LPS and FimA in mouse calvarial scalp, further confirming the differences of cytokine profile induced in vitro. Cytokine antibody arrays using toll-like receptor 2 (TLR2)-and TLR4-deficient macrophages revealed that most of the cytokines induced by P. gingivalis LPS or FimA signal through TLR2, while most of cytokines induced by live P. gingivalis signal through both TLR2 and TLR4. Interestingly, the activation of TLR2 by live P. gingivalis inhibited the release of RANTES, VCAM-1, and IL-1␣ from mouse peritoneal macrophages. A tumor necrosis factor alpha enzyme-linked immunosorbent assay further confirmed that P. gingivalis LPS and FimA activate mouse peritoneal macrophages via TLR2. These results indicate that host immune cells sense live P. gingivalis and its components differently, which translates into the expression of different inflammatory cytokine profiles.

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Section: Vol 73 2005 Cytokine Profiling Of Macrophages 939mentioning

confidence: 99%

Cytokine Profiling of Macrophages Exposed toPorphyromonas gingivalis, Its Lipopolysaccharide, or Its FimA Protein

et al. 2005

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“…For instance, CCL2 has been shown to recruit monocytes to tumors [40,41]. However, we previously investigated tumorderived CCL2 expression and reported that it does not contribute to immunogenicity of the 4T1 tumor or macrophage effector function [42,43].…”

Section: Discussionmentioning

confidence: 96%

Tumor-derived CCL5 does not contribute to breast cancer progression

Jayasinghe

Golden

Nair

et al. 2007

Breast Cancer Res Treat

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Besides functioning as a chemotactic factor, CCL5 has been associated with progression of disease in women with breast cancer, immune modulation and metastasis. Here we asked whether CCL5 produced by tumor cells contributed to growth or metastasis of breast cancer. For this purpose, we used two murine mammary carcinomas, the 4T1 tumor which is metastatic and constitutively expresses CCL5, and the 168 tumor which is not metastatic and does not constitutively express CCL5. RNA interference was used to inhibit CCL5 expression from the 4T1 tumor, and a CCL5 transgene was used to express CCL5 by the 168 tumor. Six different clones of 4T1 that exhibited stable reduction in CCL5 expression, and three different clones of 168 that exhibited stable CCL5 expression were compared to the parental tumors and vector transfected controls. Significantly, in both models, tumor-derived CCL5 expression did not correlate with MHC expression, growth rate, or metastatic ability of the tumors. These results show that tumor-derived CCL5 expression alone does not make a significant contribution to breast cancer progression.

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“…At the initial interaction with macrophages, P. gingivalis induced chemokines (e.g., MCP-1, MIP-1␤, and PARC) involved in macrophage and neutrophil recruitment and in the antigen-specific T helper cell type 1 immune response (14,47). However, this immune response may be suppressed after 24 h of exposure to P. gingivalis, since those chemokines, along with DMC/CCL22 and NAP-2, were dramatically reduced or disappeared completely after that time ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Identification of Proteins Differentially Expressed in Human Monocytes Exposed toPorphyromonas gingivalisand Its Purified Components by High-Throughput Immunoblotting

Zhou

Amar

2006

Infect Immun

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To characterize the roles of Porphyromonas gingivalis and its components in disease processes, we investigated the cytokine profiles induced by live P. gingivalis, its lipopolysaccharide (LPS), and its major fimbrial protein, fimbrillin (FimA). A cytokine antibody array revealed that human monocyte-derived macrophages were induced to produce chemokines (e.g., monocyte chemoattractant protein 1, macrophage inflammatory protein 1␤ [MIP-1␤], and MIP-3␣) as early as 1 h after exposure to P. gingivalis, with production declining after 24 h of exposure. As expected, an extensive repertoire of inflammatory mediators increased subsequent to infection, most predominantly tumor necrosis factor alpha (TNF-␣), interleukin 1␤ (IL-1␤), IL-6, IL-10, and granulocyte-macrophage colony-stimulating factor. The induction of cytokines by P. gingivalis was not triggered simply by bacterial cell surface components, since purified P. gingivalis LPS and FimA induced similar patterns of cytokines, while the pattern of cytokines induced by live P. gingivalis was significantly different, indicating that the host defense system senses live bacteria differently than it does the cell surface components LPS and FimA. To further understand the mechanisms by which live P. gingivalis and its components exert their effects, we used a high-throughput immunoblot screening approach , and other fundamental cellular processes (e.g., clathrin heavy-chain polypeptide, culreticulin, and Ras-associated protein RAB27A) was found to be modulated differentially by P. gingivalis, LPS, and FimA. These differential changes are interpreted as preferential signal pathway activation in host immune/inflammatory responses to P. gingivalis infection.

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Impact of tumor-derived CCL2 on T cell effector function

Cited by 34 publications

References 21 publications

Cytokine Profiling of Macrophages Exposed toPorphyromonas gingivalis, Its Lipopolysaccharide, or Its FimA Protein

Cytokine Profiling of Macrophages Exposed toPorphyromonas gingivalis, Its Lipopolysaccharide, or Its FimA Protein

Tumor-derived CCL5 does not contribute to breast cancer progression

Identification of Proteins Differentially Expressed in Human Monocytes Exposed toPorphyromonas gingivalisand Its Purified Components by High-Throughput Immunoblotting

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