Angiogenic activity of human CC chemokine CCL15 in vitro and in vivo

Hwang, Jung-Su; Kim, Chan Woo; Son, Kyung-No; Han, Kunsoo; Lee, Kyung Hee; Kleinman, Hynda K.; Ko, Jesang; Na, Doe Sun; Kwon, Byoung S.; Gho, Yong Song; Kim, Jiyoung

doi:10.1016/j.febslet.2004.06.023

Cited by 72 publications

(53 citation statements)

References 26 publications

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“…Consistent with this upregulation of fibrogenic factors, the SPRY1 gene, an antagonist of FGFs, was significantly reduced in Th22 cells. A potential role for Th22 in remodeling or repair of the epithelial barrier is further supported by the chemokine expression pattern characterized by CCL7, involved in tissue fibrosis (39), and CCL15 and possibly CCL23 splice variant 2, both implicated in angiogenesis (40,41). We note that results with CCL23 splice variant 1 contradicted this finding ( Figure 4C), but earlier publications did not clarify which isoform was detected.…”

Section: Figurecontrasting

confidence: 56%

Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling

et al. 2009

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Th subsets are defined according to their production of lineage-indicating cytokines and functions. In this study, we have identified a subset of human Th cells that infiltrates the epidermis in individuals with inflammatory skin disorders and is characterized by the secretion of IL-22 and TNF-α, but not IFN-γ, IL-4, or IL-17. In analogy to the Th17 subset, cells with this cytokine profile have been named the Th22 subset. Th22 clones derived from patients with psoriasis were stable in culture and exhibited a transcriptome profile clearly separate from those of Th1, Th2, and Th17 cells; it included genes encoding proteins involved in tissue remodeling, such as FGFs, and chemokines involved in angiogenesis and fibrosis. Primary human keratinocytes exposed to Th22 supernatants expressed a transcriptome response profile that included genes involved in innate immune pathways and the induction and modulation of adaptive immunity. These proinflammatory Th22 responses were synergistically dependent on IL-22 and TNF-α. Furthermore, Th22 supernatants enhanced wound healing in an in vitro injury model, which was exclusively dependent on IL-22. In conclusion, the human Th22 subset may represent a separate T cell subset with a distinct identity with respect to gene expression and function, present within the epidermal layer in inflammatory skin diseases. Future strategies directed against the Th22 subset may be of value in chronic inflammatory skin disorders.

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Section: Figurecontrasting

confidence: 56%

Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling

et al. 2009

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“…Concomitant down-regulation of the Mn chemoattractants CCL2 and CCL8 and of their receptors CCR2 and CCR5 (2) was in fact observed in response to hypoxia. Similarly, we found down-regulation of CCL15, a chemoattractant for neutrophils, monocytes, and lymphocytes (76), and CCL23, a chemokine mediating resting T cell and Mn chemotaxis (77), and of their common receptor CCR1. Collectively, these data indicate that a dynamic change in chemokine/receptor expression profile occurs in Mn within hypoxic tissues.…”

Section: Discussionmentioning

confidence: 76%

Hypoxia Modifies the Transcriptome of Primary Human Monocytes: Modulation of Novel Immune-Related Genes and Identification Of CC-Chemokine Ligand 20 as a New Hypoxia-Inducible Gene

Bosco

Puppo

Santangelo

et al. 2006

The Journal of Immunology

182

219

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Peripheral blood monocytes migrate to and accumulate in hypoxic areas of inflammatory and tumor lesions. To characterize the molecular bases underlying monocyte functions within a hypoxic microenvironment, we investigated the transcriptional profile induced by hypoxia in primary human monocytes using high-density oligonucleotide microarrays. Profound changes in the gene expression pattern were detected following 16 h exposure to 1% O2, with 536 and 677 sequences showing at least a 1.5-fold increase and decrease, respectively. Validation of this analysis was provided by quantitative RT-PCR confirmation of expression differences of selected genes. Among modulated genes, 74 were known hypoxia-responsive genes, whereas the majority were new genes whose responsiveness to hypoxia had not been previously described. The hypoxic transcriptome was characterized by the modulation of a significant cluster of genes with immunological relevance. These included scavenger receptors (CD163, STAB1, C1qR1, MSR1, MARCO, TLR7), immunoregulatory, costimulatory, and adhesion molecules (CD32, CD64, CD69, CD89, CMRF-35H, ITGB5, LAIR1, LIR9), chemokines/cytokines and receptors (CCL23, CCL15, CCL8, CCR1, CCR2, RDC1, IL-23A, IL-6ST). Furthermore, we provided conclusive evidence of hypoxic induction of CCL20, a chemoattractant for immature dendritic cells, activated/memory T lymphocytes, and naive B cells. CCL20 mRNA up-regulation was paralleled by increased protein expression and secretion. This study represents the first transcriptome analysis of hypoxic primary human monocytes, which provides novel insights into monocyte functional behavior within ischemic/hypoxic tissues. CCL20 up-regulation by hypoxia may constitute an important mechanism to promote recruitment of specific leukocyte subsets at pathological sites and may have implications for the pathogenesis of chronic inflammatory diseases.

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“…One milliliter control medium (DMEM 5% FCS) containing recombinant human growth factors or cytokines MIP-1d, MIP-3a, IGFBP-2, or PDGF-BB (20 ng/mL, all from Peprotech), angiogenin (Novoprotein) (100 ng/mL), inhibitor PD98059 (50 mM), or conditioned medium were added in the lower compartment. Neutralizing antibodies against human MIP1d (R&D Systems) (10 mg/mL) [47] and MIP-3a (Peprotech) (10 mg/mL) [48] as well as control IgG were used. After 18 h of migration, cells were fixed with methanol at -20°C for 2 min.…”

Section: Cell Migration Assaysmentioning

confidence: 99%

Inflammatory Chemokines MIP-1δ and MIP-3α Are Involved in the Migration of Multipotent Mesenchymal Stromal Cells Induced by Hepatoma Cells

Lejmi

Perriraz

Clément³

et al. 2015

Stem Cells and Development

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In vivo, bone marrow-derived multipotent mesenchymal stromal cells (MSC) have been identified at sites of tumors, suggesting that specific signals mobilize and activate MSC to migrate to areas surrounding tumors. The signals and migratory mechanisms that guide MSC are not well understood. Here, we investigated the migration of human MSC induced by conditioned medium of Huh-7 hepatoma cells (Huh-7 CM). Using a transwell migration system, we showed that human MSC migration was increased in the presence of Huh-7 CM. Using a human cytokine antibody array, we detected increased levels of MIP-1d and MIP-3a in Huh-7 CM. Recombinant chemokines MIP-1d and MIP-3a induced MSC migration. Anti-MIP-1d and anti-MIP-3a antibodies added to Huh-7 CM decreased MSC migration, further suggesting that MIP-1d and MIP-3a were implicated in the Huh-7 CM-induced MSC migration. By real-time polymerase chain reaction, we observed an absence of chemokine receptors CCR2 and CXCR2 and low expression of CCR1, CCR5, and CCR6 in MSC. Expression of these chemokine receptors was not regulated by Huh-7 CM. Furthermore, matrix metalloproteinase 1 (MMP-1) expression was strongly increased in MSC after incubation with Huh-7 CM, suggesting that MSC migration depends on MMP-1 activity. The signaling pathway MAPK/ERK was activated by Huh-7 CM but its inhibition by PD98059 did not impair Huh-7 CM-induced MSC migration. Further, long-term incubation of MSC with MIP-1d increased a-smooth muscle actin expression, suggesting its implication in the Huh-7 CM-induced evolvement of MSC into myofibroblasts. In conclusion, we report that two inflammatory cytokines, MIP-1d and MIP-3a, are able to increase MSC migration in vitro. These cytokines might be responsible for migration and evolvement of MSC into myofibroblasts around tumors.

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Angiogenic activity of human CC chemokine CCL15 in vitro and in vivo

Cited by 72 publications

References 26 publications

Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling

Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling

Hypoxia Modifies the Transcriptome of Primary Human Monocytes: Modulation of Novel Immune-Related Genes and Identification Of CC-Chemokine Ligand 20 as a New Hypoxia-Inducible Gene

Inflammatory Chemokines MIP-1δ and MIP-3α Are Involved in the Migration of Multipotent Mesenchymal Stromal Cells Induced by Hepatoma Cells

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