In Vivo Interstitial Migration of Primitive Macrophages Mediated by JNK-Matrix Metalloproteinase 13 Signaling in Response to Acute Injury

Zhang, Yong; Bai, Xuetao; Zhu, Kunfu; Jin, Y.; Deng, Min; Han, Le; Fu, Yanfang; Chen, Yi; Zhu, Jiang; Look, A. Thomas; Kanki, John P.; Zhu, Chen; Chen, Sai‐Juan; Liu, Ting Xi

doi:10.4049/jimmunol.181.3.2155

Cited by 88 publications

(101 citation statements)

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“…As described in our previous reports (9,12), transgenic zebrafish embryo (TG:zlyz-EGFP) with tail transection was applied to evaluate the effect of natural products on zebrafish leukocyte migration. The natural product library was supplied by the Kunming Institute of Botany, Chinese Academy of Sciences.…”

Section: Plasmid Constructionmentioning

confidence: 99%

“…The primary Abs in this study are specific for HSP90a, HSP90b, HSP70, His-tag, p-AKT, AKT, p-p38, p38, p-ERK, and ERK (Cell signaling Technology). Extraction of whole zebrafish embryo protein was described in our previous work (9).…”

Section: Western Blot Analysismentioning

confidence: 99%

“…Recently, the zebrafish model has been used to analyze the dynamic course of leukocyte chemotactic migration in vivo, which facilitates novel insights into certain inflammatory diseases that involve leukocytes. Thus, zebrafish is an ideal model organism to study the biological behavior of leukocytes through live imaging techniques (8)(9)(10)(11). We previously constructed a transgenic zebrafish line TG:zlyz-enhanced GFP (EGFP) for tracking leukocyte migration in response to acute injury in vivo (9).…”

mentioning

confidence: 99%

“…Thus, zebrafish is an ideal model organism to study the biological behavior of leukocytes through live imaging techniques (8)(9)(10)(11). We previously constructed a transgenic zebrafish line TG:zlyz-enhanced GFP (EGFP) for tracking leukocyte migration in response to acute injury in vivo (9). In TG:zlyz-EGFP embryos, EGFP + cells mainly represented primitive macrophages before 36 h postfertilization (hpf), whereas in the later stage after 48 hpf of embryos, the EGFP + cells contained monocytes/macrophages and neutrophils, both of which are called "leukocytes" and play an important role in innate immunity (9,12).…”

mentioning

confidence: 99%

“…We previously constructed a transgenic zebrafish line TG:zlyz-enhanced GFP (EGFP) for tracking leukocyte migration in response to acute injury in vivo (9). In TG:zlyz-EGFP embryos, EGFP + cells mainly represented primitive macrophages before 36 h postfertilization (hpf), whereas in the later stage after 48 hpf of embryos, the EGFP + cells contained monocytes/macrophages and neutrophils, both of which are called "leukocytes" and play an important role in innate immunity (9,12). Thus, we refer these EGFP + cells in the TG:zlyz-EGFP embryos (at 3 d postfertilization [dpf]) as leukocytes and use this zebrafish model to identify drug leads that inhibit interstitial leukocyte migration (12,13 Heat shock protein (HSP)90 is a highly conserved molecular chaperone that regulates diverse physiological and pathological processes.…”

mentioning

confidence: 99%

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Vibsanin B Preferentially Targets HSP90β, Inhibits Interstitial Leukocyte Migration, and Ameliorates Experimental Autoimmune Encephalomyelitis

Deng

Shao

et al. 2015

The Journal of Immunology

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Interstitial leukocyte migration plays a critical role in inflammation and offers a therapeutic target for treating inflammation-associated diseases such as multiple sclerosis. Identifying small molecules to inhibit undesired leukocyte migration provides promise for the treatment of these disorders. In this study, we identified vibsanin B, a novel macrocyclic diterpenoid isolated from Viburnum odoratissimum Ker-Gawl, that inhibited zebrafish interstitial leukocyte migration using a transgenic zebrafish line (TG:zlyz–enhanced GFP). We found that vibsanin B preferentially binds to heat shock protein (HSP)90β. At the molecular level, inactivation of HSP90 can mimic vibsanin B’s effect of inhibiting interstitial leukocyte migration. Furthermore, we demonstrated that vibsanin B ameliorates experimental autoimmune encephalomyelitis in mice with pathological manifestation of decreased leukocyte infiltration into their CNS. In summary, vibsanin B is a novel lead compound that preferentially targets HSP90β and inhibits interstitial leukocyte migration, offering a promising drug lead for treating inflammation-associated diseases.

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Section: Plasmid Constructionmentioning

confidence: 99%

Section: Western Blot Analysismentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Vibsanin B Preferentially Targets HSP90β, Inhibits Interstitial Leukocyte Migration, and Ameliorates Experimental Autoimmune Encephalomyelitis

Deng

Shao

et al. 2015

The Journal of Immunology

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Upregulation of Runt‐Related Transcription Factor‐2 Through CCAAT Enhancer Binding Protein‐β Signaling Pathway in Microglial BV‐2 Cells Exposed to ATP

Nakazato

Takarada

Ikeno

et al. 2015

Journal Cellular Physiology

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We have shown constitutive expression of the master regulator of osteoblastogenesis, runt-related transcription factor-2 (Runx2), by microglia cells outside bone. Here, we attempted to evaluate the pathological significance of Runx2 in microglial BV-2 cells exposed to ATP at a high concentration. Marked upregulation of Runx2 transcript and protein expression was seen in cells exposed to 1 mM ATP for a period longer than 30 min without inducing cytotoxicity. The Runx2 upregulation by ATP was prevented by extracellular and intracellular Ca(2+) chelators, while thapsigargin upregulated Runx2 expression alone without affecting the upregulation by ATP. A calmodulin antagonist prevented the upregulation by ATP, with calcineurin inhibitors being ineffective. Although ATP markedly increased nuclear levels of nuclear factor of activated T cell-2 (NFAT2), Runx2 promoter activity was not simulated by the introduction of either NFAT1 or NFAT2, but facilitated by that of CCAAT enhancer binding protein-α (C/EBPα), C/EBPβ and nuclear factor (erythroid-derived 2)-like-2 (Nrf2). Exposure to ATP up-regulated C/EBPβ and Nrf2, but not C/EBPα, expression, in addition to increasing nuclear levels of respective corresponding proteins. Runx2 upregulation by ATP was deteriorated by knockdown of C/EBPβ but not by that of Nrf2, however, while exposure to ATP up-regulated matrix metalloproteinase-13 (Mmp13) expression in a Runx2-dependent manner. Overexpression of Runx2 up-regulated Mmp13 expression with promoted incorporation of fluorescent beads into BV-2 cells without ATP. These results suggest that extracellular ATP up-regulates Runx2 expression through activation of the C/EBPβ signaling in a calmodulin-dependent manner to play a pivotal role in phagocytosis in microglial BV-2 cells.

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Neutrophil Motility In Vivo Using Zebrafish

Mathias

Walters

Huttenlocher

2009

Methods in Molecular Biology

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Zebrafish have emerged as a powerful model organism to study neutrophil chemotaxis and inflammation in vivo. Studies of neutrophil chemotaxis in animal models have previously been hampered both by the limited number of specimens available for analysis and by the need for invasive procedures to perform intravital microscopy. Due to the transparency and cell permeability of zebrafish embryos these limitations are circumvented, and the zebrafish system is amenable to both live time-lapse imaging of neutrophil chemotaxis and for screening of the effects of chemical compounds on the inflammatory response in vivo. Here, we describe methods to analyze neutrophil-directed migration toward wounds using both fixed embryos by myeloperoxidase activity assay, and live embryos by time-lapse microscopy. Further, methods are described for the evaluation of the effects of chemical compounds on neutrophil motility and the innate immune responses in zebrafish embryos.

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In Vivo Interstitial Migration of Primitive Macrophages Mediated by JNK-Matrix Metalloproteinase 13 Signaling in Response to Acute Injury

Abstract: MaterialSupplementary http://www.jimmunol.org/content/suppl/2008/07/18/181.3.2155.DC1

Cited by 88 publications

References 58 publications

Vibsanin B Preferentially Targets HSP90β, Inhibits Interstitial Leukocyte Migration, and Ameliorates Experimental Autoimmune Encephalomyelitis

Vibsanin B Preferentially Targets HSP90β, Inhibits Interstitial Leukocyte Migration, and Ameliorates Experimental Autoimmune Encephalomyelitis

Upregulation of Runt‐Related Transcription Factor‐2 Through CCAAT Enhancer Binding Protein‐β Signaling Pathway in Microglial BV‐2 Cells Exposed to ATP

Neutrophil Motility In Vivo Using Zebrafish

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