SUMF2 interacts with interleukin‐13 and inhibits interleukin‐13 secretion in bronchial smooth muscle cells

Liang, Hongyan; Li, Zhengjun; Li, Xue; Jiang, Xiaofeng; Liu, Fang

doi:10.1002/jcb.22336

Cited by 9 publications

(8 citation statements)

References 24 publications

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“…Production of IL-13 and infiltration of IL-13-postive cells in the submucosal region of the airway has been associated with AHR (34,35). In addition to T H 2 lymphocytes, IL-13 is secreted by many cell types in the asthmatic airway, including macrophages (36), mast cells (37), airway smooth muscle cells (38), and airway epithelial cells (39). Our histologic examination of endobronchial biopsy airway tissue sections from these patients indicated the presence of inflammatory cells that may be capable of producing IL-13 and stimulating airway fibroblast invasion.…”

Section: Discussionmentioning

confidence: 91%

Airway Fibroblasts in Asthma Manifest an Invasive Phenotype

Ingram

Huggins

Church

et al. 2011

Am J Respir Crit Care Med

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Rationale: Invasive cell phenotypes have been demonstrated in malignant transformation, but not in other diseases, such as asthma. Cellular invasiveness is thought to be mediated by transforming growth factor (TGF)-b1 and matrix metalloproteinases (MMPs). IL-13 is a key T H 2 cytokine that directs many features of airway remodeling through TGF-b1 and MMPs. Objectives: We hypothesized that, in human asthma, IL-13 stimulates increased airway fibroblast invasiveness via TGF-b1 and MMPs in asthma compared with normal controls. Methods: Fibroblasts were cultured from endobronchial biopsies in 20 subjects with mild asthma (FEV 1 : 90 6 3.6% pred) and 17 normal control subjects (FEV 1 : 102 6 2.9% pred) who underwent bronchoscopy. Airway fibroblast invasiveness was investigated using Matrigel chambers. IL-13 or IL-13 with TGF-b1 neutralizing antibody or pan-MMP inhibitor (GM6001) was added to the lower chamber as a chemoattractant. Flow cytometry and immunohistochemistry were performed in a subset of subjects to evaluate IL-13 receptor levels. Measurements and Main Results: IL-13 significantly stimulated invasion in asthmatic airway fibroblasts, compared with normal control subjects. Inhibitors of both TGF-b1 and MMPs blocked IL-13-induced invasion in asthma, but had no effect in normal control subjects. At baseline, in airway tissue, IL-13 receptors were expressed in significantly higher levels in asthma, compared with normal control subjects. In airway fibroblasts, baseline IL-13Ra2 was reduced in asthma compared with normal control subjects. Conclusions: IL-13 potentiates airway fibroblast invasion through a mechanism involving TGF-b1 and MMPs. IL-13 receptor subunits are differentially expressed in asthma. These effects may result in IL-13-directed airway remodeling in asthma.

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Section: Discussionmentioning

confidence: 91%

Airway Fibroblasts in Asthma Manifest an Invasive Phenotype

Ingram

Huggins

Church

et al. 2011

Am J Respir Crit Care Med

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“…At deep RNASeq in GENE study samples, expression of sulfatase modifying factor 2 (SUMF2) was regulated by LPS in blood and PBMCs and was identified in the eQTL analysis in multiple tissues. SUMF2 interacts with interleukin-13 (IL-13), a cytokine associated with allergic inflammation, and its expression in lymphocytes was shown to inhibit secretion of IL-13 (34). IL-13 promotes activation of alternative M2 monocyte/macrophages, thereby inhibiting pro-inflammatory cytokines and chemokines (35).…”

Section: Discussionmentioning

confidence: 99%

Integrative genomics identifies 7p11.2 as a novel locus for fever and clinical stress response in humans

Ferguson

Meyer

et al. 2014

Human Molecular Genetics

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Fever predicts clinical outcomes in sepsis, trauma and during cardiovascular stress, yet the genetic determinants are poorly understood. We used an integrative genomics approach to identify novel genomic determinants of the febrile response to experimental endotoxemia. We highlight multiple integrated lines of evidence establishing the clinical relevance of this novel fever locus. Through genome-wide association study (GWAS) of evoked endotoxemia (lipopolysaccharide (LPS) 1 ng/kg IV) in healthy subjects of European ancestry we discovered a locus on chr7p11.2 significantly associated with the peak febrile response to LPS (top single nucleotide polymorphism (SNP) rs7805622, P = 2.4 × 10 −12 ), as well as with temperature fluctuation over time. We replicated this association in a smaller independent LPS study (rs7805622, P = 0.03). In clinical translation, this locus was also associated with temperature and mortality in critically ill patients with trauma or severe sepsis. The top GWAS SNPs are not located within protein-coding genes, but have significant cis-expression quantitative trait loci (eQTL) associations with expression of a cluster of genes ∼400 kb upstream, several of which (SUMF2, CCT6A, GBAS) are regulated by LPS in vivo in blood cells. LPS-and cold-treatment of adipose stromal cells in vitro suggest genotype-specific modulation of eQTL candidate genes (PSPH). Several eQTL genes were up-regulated in brown and white adipose following cold exposure in mice, highlighting a potential role in thermogenesis. Thus, through genomic interrogation of experimental endotoxemia, we identified and replicated a novel fever locus on chr7p11.2 that modulates clinical responses in trauma and sepsis, and highlight integrated in vivo and in vitro evidence for possible novel cis candidate genes conserved across human and mouse.

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“…Our previous studies have shown that in addition to interacting with IL-13 receptors, SUMF2 interacts with IL-13. Furthermore, SUMF2 inhibits the secretion of IL-13 independently of IL-13 glycosylation (Liang et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…When we induced transient SUMF2 expression in lymphocytes, we found that amounts of the 12-kDa form of intracellular IL-13 were significantly increased, whereas levels of IL-13 in lymphocyte culture supernatants were significantly reduced. In addition, blocking N-glycosylation via treatment with tunicamycin eliminated the 17-kDa form of intracellular IL-13 but failed to promote the secretion of IL-13 by bronchial smooth muscle cells (Liang et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Sos recruitment system for the analysis of the interaction between sulfatase-modifying factor 2 subtypes and interleukin-13

Zhang¹,

Liang²,

Chun³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Interleukin (IL)-13 is a central mediator in allergic asthma. Our previous results have indicated that sulfatase-modifying factor 2 (SUMF2) interacts with IL-13 and inhibits its secretion. In this study, we investigated the interactions between SUMF2 subtypes and 2 types of IL-13. Wild type IL-13 (wh-IL-13) and its mutated counterpart (mh-IL-13) were analyzed and cloned into pSos yeast expression vectors. Protein was expressed in host cdc25H yeast strains. A quartet of agar growth plates was prepared for the yeast twohybrid system, which was used to detect IL-13 and SUMF2 subtype interactions. Both yeast expression vectors, pSos/whIL-13 and pSos/ whIL-13, and recombinant expression vectors for the 5 subtypes of SUMF2 (pMyr/SUMF2-Vx) were constructed. Our data showed that all of the SUMF2 subtypes bound to whIL-13 and mhIL-13 in the CytoTrap system. Five SUMF2 subtypes -SUMF2-V2, SUMF2-V3, 5665©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 12 (4): 5664-5672 (2013) SUMF2 subtype interaction with IL-13 SUMF2-V4, SUMF2-V5, and SUMF2-V7 -interacted with whIL-13 and mhIL-13. These subtypes may contribute to allergic asthma by mediating IL-13 release.

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SUMF2 interacts with interleukin‐13 and inhibits interleukin‐13 secretion in bronchial smooth muscle cells

Cited by 9 publications

References 24 publications

Airway Fibroblasts in Asthma Manifest an Invasive Phenotype

Airway Fibroblasts in Asthma Manifest an Invasive Phenotype

Integrative genomics identifies 7p11.2 as a novel locus for fever and clinical stress response in humans

Sos recruitment system for the analysis of the interaction between sulfatase-modifying factor 2 subtypes and interleukin-13

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