The Healing Skin Wound: A Novel Site of Action of the Chemokine C10

Kaesler, Susanne; Regenbogen, Johannes; Durka, Silke; Goppelt, Andreas; Werner, Sabine

doi:10.1006/cyto.2001.0981

Cited by 16 publications

(14 citation statements)

References 23 publications

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“…In order to determine any detrimental effects on wound healing, wounding was performed as previously described (47,48). We inflicted a circular wound 3 mm in diameter with a dermal punch (Miltex Inc.) on the upper backs of BALB/c mice (n = 4), 10 days after the last of 3 immunizations at 1-week intervals, and measured the time until complete wound closure.…”

Section: Discussionmentioning

confidence: 99%

Targeting tumor-associated fibroblasts improves cancer chemotherapy by increasing intratumoral drug uptake

Loeffler

Krüger²,

Niethammer³

et al. 2006

Journal of Clinical Investigation

558

422

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Tumor-associated fibroblasts are key regulators of tumorigenesis. In contrast to tumor cells, which are genetically unstable and mutate frequently, the presence of genetically more stable fibroblasts in the tumor-stromal compartment makes them an optimal target for cancer immunotherapy. These cells are also the primary source of collagen type I, which contributes to decreased chemotherapeutic drug uptake in tumors and plays a significant role in regulating tumor sensitivity to a variety of chemotherapies. To specifically kill tumor-associated fibroblasts, we constructed an oral DNA vaccine targeting fibroblast activation protein (FAP), which is specifically overexpressed by fibroblasts in the tumor stroma. Through CD8 + T cell-mediated killing of tumor-associated fibroblasts, our vaccine successfully suppressed primary tumor cell growth and metastasis of multidrug-resistant murine colon and breast carcinoma. Furthermore, tumor tissue of FAP-vaccinated mice revealed markedly decreased collagen type I expression and up to 70% greater uptake of chemotherapeutic drugs. Most importantly, pFap-vaccinated mice treated with chemotherapy showed a 3-fold prolongation in lifespan and marked suppression of tumor growth, with 50% of the animals completely rejecting a tumor cell challenge. This strategy opens a new venue for the combination of immuno-and chemotherapies.

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Section: Discussionmentioning

confidence: 99%

Targeting tumor-associated fibroblasts improves cancer chemotherapy by increasing intratumoral drug uptake

Loeffler

Krüger²,

Niethammer³

et al. 2006

Journal of Clinical Investigation

558

422

View full text Add to dashboard Cite

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“…In the only published study of CCL9/MIP-1␥ function in vivo, the chemokine was implicated in CD11b ϩ dendritic cell recruitment to murine Peyer's patches (58). In vivo studies of the function of CCL6/C10 focus on mRNA and protein induction in murine inflammation models; in some models, the induction occurs early and is required for leukocyte recruitment (57,59,60), whereas in other models, CCL6/C10 is induced late and is required for resolution of inflammation (56,61). In addition, in these models only the full-length chemokine was detected, because the polyclonal anti-C10 antiserum used did not recognize N-terminally truncated forms (9), presumably due to the high density of charged amino acids in the N-terminal domain.…”

Section: Discussionmentioning

confidence: 99%

Proteolytic Activation of Alternative CCR1 Ligands in Inflammation

Berahovich

Miao

Wang

et al. 2005

The Journal of Immunology

154

126

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Although chemokines CCL3/MIP-1α and CCL5/RANTES are considered to be primary CCR1 ligands in inflammatory responses, alternative CCR1 ligands have also been described. Indeed, four such chemokines, CCL6/C10/MIP-related protein-1, CCL9/MIP-1γ/MIP-related protein-2, CCL15/MIP-1δ/hemofiltrate CC chemokine-2/leukotactin-1, and CCL23/CKβ8/myeloid progenitor inhibitory factor-1, are unique in possessing a separately encoded N-terminal domain of 16–20 residues and two additional precisely positioned cysteines that form a third disulfide bridge. In vitro, these four chemokines are weak CCR1 agonists, but potency can be increased up to 1000-fold by engineered or expression-associated N-terminal truncations. We examined the ability of proinflammatory proteases, human cell supernatants, or physiological fluids to perform N-terminal truncations of these chemokines and thereby activate their functions. Remarkably, most of the proteases and fluids removed the N-terminal domains from all four chemokines, but were relatively unable to cleave the truncated forms further. The truncated chemokines exhibited up to 1000-fold increases in CCR1-mediated signaling and chemotaxis assays in vitro. In addition, N-terminally truncated CCL15/MIP-1δ and CCL23/CKβ8, but not CCL3/MIP-1α or CCL5/RANTES, were detected at relatively high levels in synovial fluids from rheumatoid arthritis patients. These data suggest that alternative CCR1 ligands are converted into potent chemoattractants by proteases released during inflammatory responses in vivo.

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“…23 Monocytes differentiate into macrophages once within the wound and play an essential role in the removal of debris and dead cells, as antigen-presenting cells, and as secretors of additional growth factors. A study by Kaesler et al 37 demonstrated that injury induced the expression of chemokine CCL-6 (C10), which is a potent chemoattractant for macrophages and may contribute to strong macrophage influx observed in cutaneous wound healing. There are differences between monocytes and macrophages within the fetal and adult wounds, with a decrease in the number and persistence of these cell types, as well as macrophages in their active and mature forms in fetal wounds.…”

Section: The Inflammatory Stage Of Wound Healingmentioning

confidence: 99%