IP-10 induces dissociation of newly formed blood vessels

Bodnar, Richard J.; Yates, Cecelia C.; Rodgers, Margaret E.; Du, Xiaoping; Wells, Alan

doi:10.1242/jcs.048793

Cited by 129 publications

(147 citation statements)

References 40 publications

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“…Although underlying mechanisms are unclear, similar effects of CXCL10 are observed in brain neuronal culture and endothelial cells in a mechanism involving CXCR3-mediated caspase 3 activation. 64,65 Leukocyte recruitment is a response to tissue injury and infection and contributes to the development and resolution of many infectious diseases. Leukocyte imaging has been used for three decades as the gold standard for the imaging and diagnosis of most infections in the immunocompetent population.…”

Section: Discussionmentioning

confidence: 99%

Critical Role of the CXCL10/C-X-C Chemokine Receptor 3 Axis in Promoting Leukocyte Recruitment and Neuronal Injury during Traumatic Optic Neuropathy Induced by Optic Nerve Crush

Liu

Zhu

et al. 2017

The American Journal of Pathology

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Traumatic optic neuropathy (TON) is an acute injury of the optic nerve secondary to trauma. Loss of retinal ganglion cells (RGCs) is a key pathological process in TON, yet mechanisms responsible for RGC death remain unclear. In a mouse model of TON, real-time noninvasive imaging revealed a dramatic increase in leukocyte rolling and adhesion in veins near the optic nerve (ON) head at 9 hours after ON injury. Although RGC dysfunction and loss were not detected at 24 hours after injury, massive leukocyte infiltration was observed in the superficial retina. These cells were identified as T cells, microglia/monocytes, and neutrophils but not B cells. CXCL10 is a chemokine that recruits leukocytes after binding to its receptor C-X-C chemokine receptor (CXCR) 3. The levels of CXCL10 and CXCR3 were markedly elevated in TON, and up-regulation of CXCL10 was mediated by STAT1/3. Deleting CXCR3 in leukocytes significantly reduced leukocyte recruitment, and prevented RGC death at 7 days after ON injury. Treatment with CXCR3 antagonist attenuated TON-induced RGC dysfunction and cell loss. In vitro co-culture of primary RGCs with leukocytes resulted in increased RGC apoptosis, which was exaggerated in the presence of CXCL10. These results indicate that leukocyte recruitment in retinal vessels near the ON head is an early event in TON and the CXCL10/CXCR3 axis has a critical role in recruiting leukocytes and inducing RGC death. (Am J Pathol 2017, 187: 352e365; http://dx

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Section: Discussionmentioning

confidence: 99%

Critical Role of the CXCL10/C-X-C Chemokine Receptor 3 Axis in Promoting Leukocyte Recruitment and Neuronal Injury during Traumatic Optic Neuropathy Induced by Optic Nerve Crush

Liu

Zhu

et al. 2017

The American Journal of Pathology

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“…Indeed, EC-mitigating mechanisms do activate during wound resolution, including those mediated by intracellular negative feedback against growth factor stimulation [e.g., Sprouty (63)], ECM remodeling processes that generate matrix-derived antiangiogenic peptides and secreted extracellular factors that promote EC apoptosis [reviewed in (62)]. Antiangiogenic factors include interferon ␥-induced protein 10 (CXCL10) (9) and matricellular proteins such as thrombospondins (36) (Fig. 8B).…”

Section: Discussionmentioning

confidence: 99%

Pigment epithelium-derived factor as a multifunctional regulator of wound healing

Wietecha

Król

Michalczyk

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Wietecha MS, Król MJ, Michalczyk ER, Chen L, Gettins PG, DiPietro LA. Pigment epithelium-derived factor as a multifunctional regulator of wound healing. Am J Physiol Heart Circ Physiol 309: H812-H826, 2015. First published July 10, 2015; doi:10.1152/ajpheart.00153.2015.-During dermal wound repair, hypoxia-driven proliferation results in dense but highly permeable, disorganized microvascular networks, similar to those in solid tumors. Concurrently, activated dermal fibroblasts generate an angiopermissive, provisional extracellular matrix (ECM). Unlike cancers, wounds naturally resolve via blood vessel regression and ECM maturation, which are essential for reestablishing tissue homeostasis. Mechanisms guiding wound resolution are poorly understood; one candidate regulator is pigment epithelium-derived factor (PEDF), a secreted glycoprotein. PEDF is a potent antiangiogenic in models of pathological angiogenesis and a promising cancer and cardiovascular disease therapeutic, but little is known about its physiological function. To examine the roles of PEDF in physiological wound repair, we used a reproducible model of excisional skin wound healing in BALB/c mice. We show that PEDF is abundant in unwounded and healing skin, is produced primarily by dermal fibroblasts, binds to resident microvascular endothelial cells, and accumulates in dermal ECM and epidermis. PEDF transcript and protein levels were low during the inflammatory and proliferative phases of healing but increased in quantity and colocalization with microvasculature during wound resolution. Local antibody inhibition of endogenous PEDF delayed vessel regression and collagen maturation during the remodeling phase. Treatment of wounds with intradermal injections of exogenous, recombinant PEDF inhibited nascent angiogenesis by repressing endothelial proliferation, promoted vascular integrity and function, and increased collagen maturity. These results demonstrate that PEDF contributes to the resolution of healing wounds by causing regression of immature blood vessels and stimulating maturation of the vascular microenvironment, thus promoting a return to tissue homeostasis after injury.

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“…Previous studies using CXCR3-deficient or IP-10-deficient mice found reduced levels of tissue-infiltrated T cells in several disease models, including inflammation and transplantation. 32,33 In addition, in vitro studies have shown that CXCR3 ligands can promote the adhesion of lymphoblasts to human endothelial cells. IL-6-triggered STAT3 phosphorylation is an important upstream signal for IP-10 production by macrophages.…”

Section: Discussionmentioning

confidence: 99%

CXCL10/IP-10 Is a Biomarker and Mediator for Kawasaki Disease

Kuo

Chang

et al. 2015

Circulation Research

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Rationale: Kawasaki disease (KD), an acute febrile vasculitis, is the most common cause of acquired heart disease in childhood; however, diagnosing KD can be difficult. Objective: To identify unique proteomic biomarkers that can be used to facilitate earlier diagnosis of KD. Methods and Results: We enrolled 214 children with fever and clinical features suggestive of KD. Of those, only 100 were diagnosed with KD. Their plasma samples were globally analyzed for cytokines, chemokines, and cell adhesion molecules using an unbiased, large-scale, quantitative protein array. This study was conducted in 3 stages: discovery, replication, and blinded validation. During the discovery phase (n [KD]=37; n [control]=20), the expression of interleukin-17F, sCD40L, E-selectin, CCL23 (myeloid progenitor inhibitory factor 1), and CXCL10 (IFN-γ-inducible protein 10 [IP-10]) were upregulated during the acute phase in patients with KD when compared with that in the controls. A notable increase was observed in the IP-10 levels (KD, 3037±226.7 pg/mL; control, 672±130.4 pg/mL; P =4.1×10 –11 ). Receiver-operating characteristic analysis of the combined discovery and replication data (n [KD]=77; n [control]=77) showed that the IP-10 level had high area under the curve values (0.94 [95% confidence interval, 0.9055–0.9778]; sensitivity, 100%; and specificity, 77%). With 1318 pg/mL as the optimal cutoff, the blinded validation study confirmed that the IP-10 levels were a good predictor of KD. With intravenous immunoglobulin treatment, the IP-10 levels returned to normal. The downstream receptor of IP-10, CXCR3, was activated in the T cells of patients with acute KD. Conclusions: IP-10 may be used as a biomarker to facilitate KD diagnosis, and it may provide clues about the pathogenesis of KD.

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IP-10 induces dissociation of newly formed blood vessels

Cited by 129 publications

References 40 publications

Critical Role of the CXCL10/C-X-C Chemokine Receptor 3 Axis in Promoting Leukocyte Recruitment and Neuronal Injury during Traumatic Optic Neuropathy Induced by Optic Nerve Crush

Critical Role of the CXCL10/C-X-C Chemokine Receptor 3 Axis in Promoting Leukocyte Recruitment and Neuronal Injury during Traumatic Optic Neuropathy Induced by Optic Nerve Crush

Pigment epithelium-derived factor as a multifunctional regulator of wound healing

CXCL10/IP-10 Is a Biomarker and Mediator for Kawasaki Disease

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