Synergy of IL-27 and TNF-α in Regulating CXCL10 Expression in Lung Fibroblasts

Dong, Shanshan; Zhang, Xuemei; He, Yujuan; Xu, Fang; Li, Dairong; Xu, Wenchun; Wang, Hong; Yin, Yibing; Cao, Ju

doi:10.1165/rcmb.2012-0340oc

Cited by 44 publications

(35 citation statements)

References 45 publications

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“…Intriguingly, IL-27 has been reported to act synergistically with other cytokines, particularly TNF-α, such that synergistic effects with IL-13 may not be surprising. 20,45,46 As expected, IL-27 stimulated CXCL9 secretion, while IL-13 (at low or high dose) had no impact on CXCL9. However, when epithelial cells were treated with IL-13 at low dose (1 ng/ml) and IL-27 added, there was a surprising synergistic increase in CXCL9 mRNA and protein.…”

Section: Discussionsupporting

confidence: 69%

IL-27 and type 2 immunity in asthmatic patients: Association with severity, CXCL9, and signal transducer and activator of transcription signaling

Xie

Mustovich

Jiang

et al. 2015

Journal of Allergy and Clinical Immunology

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Background Severe asthma may involve both innate and Type-2 cytokine associated adaptive immunity. While IL-27 has been reported to potentiate Th1 responses (including the chemokine CXCL9) and suppress Th2 responses, its function in asthma is unknown. Objective Evaluate IL-27 expression in human asthma, alone and in combination with Type-2 immunity to determine the relationship to disease severity and CXCL9 expression. Model these interactions in vitro in human bronchial epithelial cells (HBEC). Methods Bronchoalveolar lavage (BAL) cells from 87 participants were evaluated for IL-27 mRNA and protein, alone and in association with epithelial CCL26 (a marker of Type-2 activation) in relation to asthma severity and CXCL9 mRNA. HBECs cultured in air liquid interface (ALI) and stimulated with IL-27 (1–100 ng/ml) with/without IL-13 (1 ng/ml) were evaluated for CXCL9 expression by qRT-PCR and ELISA. Phosphorylated and total STAT1/3 were detected by western blot. siRNA knockdown of STAT1 or STAT3 was performed. Results BAL cell IL-27 mRNA and protein were increased in asthma. Patients with evidence for Type-2 pathway activation had higher IL-27 expression (p=0.02). Combined IL-27 and CCL26 expression associated with more severe asthma and higher CXCL9 expression (p=0.004, 0.007 respectively), while IL-27 alone was associated with milder disease. In vitro, IL-13 augmented IL-27 induced CXCL9 expression which appeared to be due to augmented STAT1 activation and reduced STAT3 activation. Conclusions IL-27, in combination with a Type-2/CCL26 signature identifies a more severe asthma phenotype, perhaps through combined effects of IL-27 and IL-13 on STAT signaling. Understanding these interactions could lead to new targets for asthma therapy.

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Section: Discussionsupporting

confidence: 69%

IL-27 and type 2 immunity in asthmatic patients: Association with severity, CXCL9, and signal transducer and activator of transcription signaling

Xie

Mustovich

Jiang

et al. 2015

Journal of Allergy and Clinical Immunology

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“…However, further characterization of the lungs for mRNA expression of cytokine or chemokines showed (ζ+)NP administration upregulated genes for two chemokines, CCL2 and CXCL10, responsible for leukocyte recruitment (36, 38). We also detected an increase in total CD11c + DCs in the lung following cationic NP administration, likely corresponding to the upregulation of these chemokines.…”

Section: Discussionmentioning

confidence: 99%

Nanoparticle surface charge impacts distribution, uptake and lymph node trafficking by pulmonary antigen-presenting cells

Fromen

Rahhal

Robbins

et al. 2016

Nanomedicine: Nanotechnology, Biology and Medicine

124

125

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Engineered nanoparticles have the potential to expand the breadth of pulmonary therapeutics, especially as respiratory vaccines. Notably, cationic nanoparticles have been demonstrated to produce superior local immune responses following pulmonary delivery; however, the cellular mechanisms of this increased response remains unknown. To this end, we systematically investigated the cellular response of lung APCS following pulmonary instillation of anionic and cationic charged nanoparticles. While nanoparticles of both surface charges were capable of trafficking to the draining lymph node and were readily internalized by alveolar macrophages, both CD11b and CD103 lung dendritic cell (DC) subtypes preferentially associated with cationic nanoparticles. Instillation of cationic nanoparticles resulted in the upregulation of Ccl2 and Cxc10, which likely contributes to the recruitment of CD11b DCs to the lung. In total, these cellular mechanisms explain the increased efficacy of cationic formulations as a pulmonary vaccine carrier and provide critical benchmarks in the design of pulmonary vaccine nanoparticles.

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“…Qiu et al reported that IL-27 could enhance CXCL10 production in TNF-α-treated human coronary artery endothelial cells [37]. Dong et al also reported that IL-27 increased CXCL10 expression in TNF-α-stimulated human lung fibroblasts [38]. Judging from our report and previous reports, we think both IL-27 and TNF-αpromote accumulation of Th1 cells in periodontal lesion by inducing CXCR3 ligands production to epithelial cells, endothelial cells, and fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

IL-27 Modulates Chemokine Production in TNF-α -Stimulated Human Oral Epithelial Cells

Hosokawa

Ozaki

et al. 2017

Cell Physiol Biochem

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Background/Aims: Interleukin-27 (IL-27) is a cytokine which belongs to the IL-12 family. However, the role of IL-27 in the pathogenesis of periodontal disease is uncertain. The aim of this study was to examine the effect of IL-27 on chemokine production in TNF-α-stimulated human oral epithelial cells (TR146). Methods: We measured chemokine production in TR146 by ELISA. We used western blot analysis to detect the phosphorylation levels of signal transduction molecules, including STAT1 and STAT3 in TR146. We used inhibitors to examine the role of STAT1 and STAT3 activation. Results: IL-27 increased CXCR3 ligands production in TNF-α-stimulated TR146. Meanwhile, IL-27 suppressed IL-8 and CCL20 production induced by TNF-α. STAT1 phosphorylation level in IL-27 and TNF-α-stimulated TR146 was enhanced in comparison to TNF-α-stimulated TR146. STAT3 phosphorylation level in IL-27-treated TR146 did not change by TNF-α. Both STAT1 inhibitor and STAT3 inhibitor decreased CXCR3 ligands production. STAT1 inhibitor overrode the inhibitory effect of IL-27 on IL-8 and CCL20 production in TNF-α-stimulated TR146. Meanwhile, STAT3 inhibitor did not modulate IL-8 and CCL20 production. Conclusion: IL-27 might control leukocyte migration in periodontal lesion by modulating chemokine production from epithelial cells.

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Synergy of IL-27 and TNF-α in Regulating CXCL10 Expression in Lung Fibroblasts

Cited by 44 publications

References 45 publications

IL-27 and type 2 immunity in asthmatic patients: Association with severity, CXCL9, and signal transducer and activator of transcription signaling

IL-27 and type 2 immunity in asthmatic patients: Association with severity, CXCL9, and signal transducer and activator of transcription signaling

Nanoparticle surface charge impacts distribution, uptake and lymph node trafficking by pulmonary antigen-presenting cells

IL-27 Modulates Chemokine Production in TNF-α -Stimulated Human Oral Epithelial Cells

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