Interferon-γ inhibits collagen phagocytosis in human fibroblasts by inducing subcortical actin assembly and reducing ability of β1 integrin to bind to collagen

Takaki, Takashi; Kobayashi, Mariko; Okubo, Kazutoshi; Takahashi, Naoyuki; Okamatsu, Yoshimasa; Mochizuki, Susumu; Yamamoto, Masahide; Hasegawa, Kohji

doi:10.1007/s00011-006-5088-0

Cited by 3 publications

(4 citation statements)

References 28 publications

(34 reference statements)

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“…Previously, Tabe et al indicated that ILK/Akt are involved in a proximal signaling pathway critical for the survival of leukemic cells within the BM microenvironment (10). Moreover, it has also been reported that exposure of human fibroblasts to IFN-γ induces a subcortical actin assembly and subsequently reduces the affinity activity of β1 integrin during its engagement with collagen (11). These results have revealed that there may be a correlation between IFN-γ and β1 integrin.…”

Section: Introductionmentioning

confidence: 99%

Adenovirus-mediated delivery of the human IFN-γ gene potentiates the cytotoxicity of daunorubicin against leukemic cells through downregulation of the α4β1 integrin/ILK/apoptosis pathway

Zhang

Wang

et al. 2013

Oncology Letters

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The recurrence of acute myeloid leukemia (AML) is primarily attributed to drug resistance and minimal residual disease. In addition, adhesion of hematopoietic tumor cells to bone marrow extracellular matrix via β1 integrins (α4β1 and α5β1) is crucial in this process. In the current study, the viability and antiapoptotic ability of U937 cells exposed to daunorubicin (DNR) were shown to be enhanced when cocultured with the mesenchymal stem cells (MSCs) or MSCs transduced with a recombinant adeno-LacZ vector (MSCs-LacZ), followed by upregulation of the adhesion rate of leukemic cells. Notably, cell viability, antiapoptotic and adhesive ability were reversed when U937 cells were cocultured with the MSCs transduced with a recombinant adeno-IFN-γ vector (MSCs-IFN-γ). Transwell assay showed that cell-cell contact is essential for the protective effects of unmodified MSC and the antitumor effects of IFN-γ-expressing MSCs. Western blot analysis and caspase activity assay results indicated that the α4β1 integrin/ILK/apoptosis pathway contributes to the combination effects of DNR and MSCs-IFN-γ, which was further confirmed by the results of the α4β1 integrin siRNA experiments. Thus, gene-modified MSCs expressing IFN-γ may enhance the cytotoxicity of DNR against leukemic cells through downregulation of the α4β1 pathway and may present a novel promising therapeutic strategy for AML.

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Section: Introductionmentioning

confidence: 99%

Adenovirus-mediated delivery of the human IFN-γ gene potentiates the cytotoxicity of daunorubicin against leukemic cells through downregulation of the α4β1 integrin/ILK/apoptosis pathway

Zhang

Wang

et al. 2013

Oncology Letters

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“…In particular, the intracellular collagen degradation is prevalent in connective tissues with a rapid turnover of collagen, including gingival tissue (21). Furthermore, inflammatory cytokines such as tumor necrosis factor‐α and interferon‐γ decrease collagen phagocytosis by gingival fibroblasts (5, 27), suggesting that the inhibition by these inflammatory cytokines of fibroblast collagen phagocytosis contributes to collagen overgrowth in inflamed gingival tissue. However, little is known about the regulatory effect of LPS from periodontopathogens on collagen phagocytosis by fibroblasts and the associated regulatory mechanisms.…”

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confidence: 99%

“…Typical HGF populations isolated from the tissues of each of the three volunteers were designated as HGF‐1, ‐2, and ‐3. Collagen phagocytic activity in HGF was determined using an assay for internalization of collagen‐coated beads, following the previously published method (27). Similar to the findings of previous studies (5, 27), when HGF were incubated with collagen‐coated beads for 3 h in medium with 0.5% bovine serum albumin (BSA), the percentage of cells that contained ingested beads was increased (mean 22.3%) (data not shown).…”

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“…Since the binding of collagen is an early and potentially rate‐limiting step in collagen phagocytosis by fibroblasts, we further examined the effect of A. actinomycetemcomitans LPS on the binding of collagen‐coated beads to HGF, according to the previously described method (27). Similar to our previous findings (27), the number of collagen‐coated beads bound to the cell layer was increased 1 h after adding beads to the culture (data not shown). As expected, the increased bead binding was weakly, but significantly, enhanced by pretreatment with LPS at concentrations above 100 ng/ml for 72 h (vs. control; mean 1.3‐fold increase at 100 ng/ml, 1.4‐fold increase at 1000 ng/ml) (Fig.…”

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confidence: 99%

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Actinobacillus actinomycetemcomitans lipopolysaccharide stimulates collagen phagocytosis by human gingival fibroblasts

Takahashi

Kobayashi

Takaki

et al. 2008

Oral Microbiology and Immunology

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These results suggest that A. actinomycetemcomitans LPS disturbs the homeostasis of collagen metabolism within gingival tissue by facilitating collagen phagocytosis by gingival fibroblasts, and serum sCD14 and LBP positively regulate the action of LPS. In addition, the PI3K/Akt signaling is thought to partially mediate the LPS/LBP-stimulated collagen phagocytic pathway, which may be dependent on actin cytoskeletal rearrangement.

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Cell mediated ECM-degradation as an emerging tool for anti-fibrotic strategy

Zhao,

Sun,

Lyu

et al. 2023

Cell Regen

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Investigation into the role of cells with respect to extracellular matrix (ECM) remodeling is still in its infancy. Particularly, ECM degradation is an indispensable process during the recovery from fibrosis. Cells with ECM degradation ability due to the secretion of various matrix metalloproteinases (MMPs) have emerged as novel contributors to the treatment of fibrotic diseases. In this review, we focus on the ECM degradation ability of cells associated with the repertoire of MMPs that facilitate the attenuation of fibrosis through the inhibition of ECM deposition. Besides, innovative approaches to engineering and characterizing cells with degradation ability, as well as elucidating the mechanism of the ECM degradation, are also illustrated. Studies conducted to date on the use of cell-based degradation for therapeutic purposes to combat fibrosis are summarized. Finally, we discuss the therapeutic potential of cells with high degradation ability, hoping to bridge the gap between benchside research and bedside applications in treating fibrotic diseases.

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Interferon-γ inhibits collagen phagocytosis in human fibroblasts by inducing subcortical actin assembly and reducing ability of β1 integrin to bind to collagen

Cited by 3 publications

References 28 publications

Adenovirus-mediated delivery of the human IFN-γ gene potentiates the cytotoxicity of daunorubicin against leukemic cells through downregulation of the α4β1 integrin/ILK/apoptosis pathway

Adenovirus-mediated delivery of the human IFN-γ gene potentiates the cytotoxicity of daunorubicin against leukemic cells through downregulation of the α4β1 integrin/ILK/apoptosis pathway

Actinobacillus actinomycetemcomitans lipopolysaccharide stimulates collagen phagocytosis by human gingival fibroblasts

Cell mediated ECM-degradation as an emerging tool for anti-fibrotic strategy

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