Human airway epithelial cells produce IP-10 (CXCL10) in vitro and in vivo upon rhinovirus infection

Spurrell, Jason; Wiehler, Shahina; Zaheer, Raza S.; Sanders, Scherer P.; Proud, David

doi:10.1152/ajplung.00397.2004

Cited by 253 publications

(322 citation statements)

References 38 publications

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“…In our studies of TON, sterile inflammation occurs in the absence of live pathogens, and we found that CXCL10 up-regulation is associated with STAT1 and STAT3 activation and its production is significantly attenuated by blocking STAT1 and STAT3 activation with Stattic. In contrast, NF-kB, a proinflammatory transcription factor regulating CXCL10 expression after viral infection, 51,52 does not participate in axonal injury-induced CXCL10 expression. To our knowledge, this is the first report that provides evidence suggesting that STAT1 and STAT3 appear to regulate CXCL10 level during sterile inflammation.…”

Section: Discussionmentioning

confidence: 85%

“…Sequence analysis revealed that the CXCL10 promoter region contains transcription factor binding sites for AP-1, NF-kB, interferon regulatory factor, and STAT. 51,52 Because activation of NF-kB has an essential role in inflammatory reactions and has been shown to induce CXCL10 expression during virus infection, 51 Quantitative PCR analysis of CXCR3 mRNA expression in control or injured retinas at 3, 6, 12, and 24 hours after TON. E: Representative images of CXCR3 immunostaining in retinal frozen sections from control and TON-performed eyes at 24 hours after TON.…”

Section: Up-regulation Of Cxcl10 In Ton Is Mediated By Statmentioning

confidence: 99%

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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: 85%

Section: Up-regulation Of Cxcl10 In Ton Is Mediated By Statmentioning

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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“…The anatomical compartment chosen for this recruitment assay is the airways, as both IP-10 and I-TAC, as well as other chemokines, have been shown to be expressed by bronchial epithelial cells especially during various inflammatory diseases, such as tuberculosis , chronic obstructive pulmonary disease (COPD) (Saetta et al, 2002), and rhinovirus infections (Spurrell et al, 2005), resulting in the recruitment of CXCR3 + lymphocytes into the airways. By instilling I-TAC or IP-10 directly into the airways, this assay models the natural environment in which these chemokines are normally expressed during inflammatory processes.…”

Section: Discussionmentioning

confidence: 99%

Development of a novel chemokine-mediated in vivo T cell recruitment assay

Campanella

Medoff

Manice

et al. 2008

Journal of Immunological Methods

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Trafficking of leukocytes to sites of inflammation is an important step in the establishment of an immune response. Chemokines are critical regulators of leukocyte trafficking and are widely studied molecules for their important role in disease and for their potential as new therapeutic targets. The ability of chemokines to induce leukocyte recruitment has been mainly measured by in vitro chemotaxis assays, which lack many components of the complex biological process of leukocyte migration and therefore provide incomplete information about chemokine function in vivo. In vivo assays to study the activity of chemokines to induce leukocyte recruitment have been difficult to establish. We describe here the development of a robust in vivo recruitment assay for CD8 + and CD4 + T lymphocytes induced by the CXCR3 ligands IP-10 (CXCL10) and I-TAC (CXCL11). For this assay, in vitro activated T lymphocytes were adoptively transferred into the peritoneum of naïve mice. Homing of these transferred T lymphocytes into the airways was measured following intratracheal instillation of chemokines. High recruitment indices were achieved that were dependent on chemokine concentration and CXCR3 expression on the transferred lymphocytes. Recruitment was also inhibited by antibodies to the chemokine. The assay models the natural condition of chemokine-mediated lymphocyte migration into the airways as chemokines are expressed in the airways during inflammation. The nature of this model allows flexibility to study wildtype and mutant chemokines and chemokine receptors and the ability to evaluate chemokine antagonists and antibodies in vivo. This assay will therefore help elucidate a deeper understanding of the chemokine system in vivo.

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“…5A) (34). Data are expressed as fold difference, as little and no significant difference was observed in baseline levels observed between each construct when nonstimulated (data not shown).…”

Section: Essential Elements In the Human Cxcl10 Promoter Region In Rementioning

confidence: 99%

TNF and IFN Synergistically Enhance Transcriptional Activation of CXCL10 in Human Airway Smooth Muscle Cells via STAT-1, NF- B, and the Transcriptional Coactivator CREB-binding Protein

Clarke

Clifford

Jindarat

et al. 2010

Journal of Biological Chemistry

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Asthmatic airway smooth muscle (ASM) expresses interferon-␥-inducible protein-10 (CXCL10), a chemokine known to mediate mast cell migration into ASM bundles that has been reported in the airways of asthmatic patients. CXCL10 is elevated in patients suffering from viral exacerbations of asthma and in patients with chronic obstructive pulmonary disease (COPD), diseases in which corticosteroids are largely ineffective. IFN␥ and TNF␣ synergistically induce CXCL10 release from human ASM cells in a steroid-insensitive manner, via an as yet undefined mechanism. We report that TNF␣ activates the classical NF-B (nuclear factor B) pathway, whereas IFN␥ activates JAK2/STAT-1␣ and that inhibition of the JAK/STAT pathway is more effective in abrogating CXCL10 release than the steroid fluticasone. The synergy observed with TNF␣ and IFN␥ together, however, did not lie at the level of NF-B activation, STAT-1␣ phosphorylation, or in vivo binding of these transcription factors to the CXCL10 promoter. Stimulation of human ASM cells with TNF␣ and IFN␥ induced histone H4 but not histone H3 acetylation at the CXCL10 promoter, although no synergism was observed when both cytokines were combined. We show, however, that TNF␣ and IFN␥ exert a synergistic effect on the recruitment of CREB-binding protein (CBP) to the CXCL10, which is accompanied by increased RNA polymerase II. Our results provide evidence that synergism between TNF␣ and IFN␥ lies at the level of coactivator recruitment in human ASM and suggest that inhibition of JAK/STAT signaling may be of therapeutic benefit in steroid-resistant airway disease.Lung diseases such as asthma and COPD 2 cause significant morbidity and mortality in Western societies. 5-10% of the asthmatic population are unresponsive to corticosteroids, the mainstay for asthma therapy, and patients with COPD are treated ineffectively with steroids. Additionally, viral exacerbations of asthma are a major cause of morbidity and mortality associated with asthma and are relatively unresponsive to steroids (1, 2).CXCL10, a member of the CXC chemokine subfamily, is a potent chemoattractant for mast cells and T lymphocytes, cells implicated in the pathophysiology of asthma and COPD. CXCL10 is elevated in the airways of asthmatic patients and has been implicated in mast cell migration to the ASM bundles (3). CXCL10 also is elevated in the bronchial mucosa and broncho alveolar lavage (BAL) fluid of subjects with moderate/severe asthma, which is largely steroid-resistant (4). Enhanced CXCL10 secretion also has been demonstrated in COPD (5-7), and more recently, it has been reported that serum CXCL10 levels are increased to a greater extent in asthmatics with acute virus-induced asthma compared with nonvirus-induced acute asthma, and increased levels are predictive of virus-induced asthma exacerbations (8). CXCL10 is released in response to IFN␥ or TNF␣ from a number of inflammatory cell types (6, 9 -12), and several reports also have shown that TNF␣ and IFN␥ synergistically enhance CXCL10 release (13-16). Given the he...

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Human airway epithelial cells produce IP-10 (CXCL10) in vitro and in vivo upon rhinovirus infection

Cited by 253 publications

References 38 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

Development of a novel chemokine-mediated in vivo T cell recruitment assay

TNF and IFN Synergistically Enhance Transcriptional Activation of CXCL10 in Human Airway Smooth Muscle Cells via STAT-1, NF- B, and the Transcriptional Coactivator CREB-binding Protein

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