Primary role of growth‐related oncogene‐α and granulocyte chemotactic protein‐2 as neutrophil chemoattractants in chronic rhinosinusitis

Rudack, Claudia; Sachse, F.; Alberty, J.

doi:10.1111/j.1365-2222.2006.02501.x

Cited by 16 publications

(13 citation statements)

References 24 publications

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“…In CF and CRS patients, CXCL6 was detected in lung epithelium goblet cells and was a more potent neutrophil chemoattractant than CXCL8, while treatment with an anti-CXCL6 antibody reduced neutrophil influx and inflammation in a mouse model of IPF (59)(60)(61)(62)(63). Similarly, CXCR6 was expressed on lung-infiltrating Th2 cells in a mouse model of asthma (62) and in asthmatic patients (61).…”

Section: Secretome Directionality and Homeostatic Processesmentioning

confidence: 99%

The Secretome Profiling of a Pediatric Airway Epithelium Infected with hRSV Identified Aberrant Apical/Basolateral Trafficking and Novel Immune Modulating (CXCL6, CXCL16, CSF3) and Antiviral (CEACAM1) Proteins

Touzelet

Broadbent

Armstrong

et al. 2020

Molecular & Cellular Proteomics

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The respiratory epithelium comprises polarized cells at the interface between the environment and airway tissues. Polarized apical and basolateral protein secretions are a feature of airway epithelium homeostasis. Human respiratory syncytial virus (hRSV) is a major human pathogen that primarily targets the respiratory epithelium. However, the consequences of hRSV infection on epithelium secretome polarity and content remain poorly understood. To investigate the hRSV-associated apical and basolateral secretomes, a proteomics approach was combined with an ex vivo pediatric human airway epithelial (HAE) model of hRSV infection (data are available via ProteomeXchange and can be accessed at https://www.ebi.ac.uk/pride/ with identifier PXD013661). Following infection, a skewing of apical/basolateral abundance ratios was identified for several individual proteins. Novel modulators of neutrophil and lymphocyte activation (CXCL6, CSF3, SECTM1 or CXCL16), and antiviral proteins (BST2 or CEACAM1) were detected in infected, but not in uninfected cultures. Importantly, CXCL6, CXCL16, CSF3 were also detected in nasopharyngeal aspirates (NPA) from hRSV-infected infants but not healthy controls. Furthermore, the antiviral activity of CEACAM1 against RSV was confirmed in vitro using BEAS-2B cells. hRSV infection disrupted the polarity of the pediatric respiratory epithelial secretome and was associated with immune modulating proteins (CXCL6, CXCL16, CSF3) never linked with this virus before. In addition, the antiviral activity of CEACAM1 against hRSV had also never been previously characterized. This study, therefore, provides novel insights into RSV pathogenesis and endogenous antiviral responses in pediatric airway epithelium.

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Section: Secretome Directionality and Homeostatic Processesmentioning

confidence: 99%

The Secretome Profiling of a Pediatric Airway Epithelium Infected with hRSV Identified Aberrant Apical/Basolateral Trafficking and Novel Immune Modulating (CXCL6, CXCL16, CSF3) and Antiviral (CEACAM1) Proteins

Touzelet

Broadbent

Armstrong

et al. 2020

Molecular & Cellular Proteomics

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“…52 In states of chronic inflammation such as inflammatory bowel disease (characterized by unremitting leukocyte infiltration in affected tissues), CXCL6 expression is selectively up-regulated in endothelial cells at sites of intestinal inflammation and ulceration. 34 Furthermore, Rudack et al 53 describe the pattern of chemokine expression in patients with chronic rhinosinusitis, a neutrophilmediated condition. CXCL6 and GRO-a were the pre-dominant chemokines produced by affected mucosa and epithelial cells.…”

Section: Cxcl6 In Pathologic Conditionsmentioning

confidence: 99%

ORIGINAL ARTICLE: CXCL6 (Granulocyte Chemotactic Protein‐2): A Novel Chemokine Involved in the Innate Immune Response of the Amniotic Cavity

Mittal

Romero

Kusanovic

et al. 2008

American J Rep Immunol

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PROBLEM-CXCL6 is a potent pro-inflammatory neutrophil chemoattractant and activator whose activity during pregnancy is not well-established. The purpose of this study was to determine if CXCL6 is present in amniotic fluid (AF) and if CXCL6 concentrations in AF change with labor (preterm and term) or intra-amniotic infection/inflammation (IAI).METHOD OF STUDY-A cross-sectional study was conducted with the following groups: 1) mid-trimester (n=65); 2) term no labor (n=20); 3) term labor (n=44); 4) patients with PTL with subsequent term delivery (n=57); 5) preterm labor (PTL) without IAI who delivered preterm (n=47); and 6) PTL with IAI (n=62). AF CXCL6 concentrations were determined by ELISA. RESULTS-CXCL6was present in all term samples, but undetectable in 64/65 mid-trimester specimens. Patients with PTL and IAI had a significantly higher median CXCL6 AF concentration than those with PTL without IAI [228.9 pg/ml (0.0-8344.8) vs. 55.7 pg/ml (0-454.4); p<0.05] and those with PTL and term delivery [41.5 pg/ml (0-279.0); p<0.05]. Median AF CXCL6 concentration did not change with spontaneous term labor [term no labor: 81.1 pg/ml (8.5-201.7) vs. term labor: 75.2 pg/ml (6.7-378.7): p=0.74]. CONCLUSIONS-1)CXCL6 is detectable in AF and its concentration increases with gestational age; 2) IAI results in increased CXCL6 AF concentrations, suggesting that CXCL6 plays a role in the deployment of an inflammatory response; 3) In contrast to related chemokines, specifically IL-8, AF CXCL6 does not appear to be involved in spontaneous term parturition. These observations are novel, and suggest a role for CXCL6 in the innate immune response to microbial invasion of the amniotic cavity.

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“…Regarding the inflammation, accumulating evidence has shown that chemokine levels play important roles in the progression of airway inflammation [ 11 – 12 ]. Among these chemokines, the CXC chemokines such as CXCL1 and CXCL8, are primarily chemotactic factors for leukocytes and are potent promoters of angiogenesis and tissue inflammation [ 13 – 14 ]. CXCL1 and -8 can bind their receptors, including CXCR1 and -2 [ 15 ] and direct the migration of circulating leukocytes to sites of inflammation or injury [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Involvement of B2 Receptor in Bradykinin-Induced Proliferation and Proinflammatory Effects in Human Nasal Mucosa-Derived Fibroblasts Isolated from Chronic Rhinosinusitis Patients

et al. 2015

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Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the sinonasal mucosa either accompanied by polyp formation (CRSwNP) or without polyps (CRSsNP). CRSsNP accounts for the majority of CRS cases and is characterized by fibrosis and neutrophilic inflammation. However, the pathogenesis of CRS, especially CRSsNP, remains unclear. Immunohistochemistry of CRSsNP specimens in the present study showed that the submucosa, perivascular areas, and the mucous glands were abundant in fibroblasts. Therefore, we investigated the effects bradykinin (BK), an autacoid known to participate in inflammation, on human CRSsNP nasal mucosa-derived fibroblasts (NMDFs). BK increased CXCL1 and -8 secretion and mRNA expression with EC50 ranging from 0.15~0.35 μM. Moreover, BK enhanced cell proliferation and upregulated the expressions of proinflammatory molecules, including cell adhesion molecules (CAMs) and cyclooxygenase (COX)-1 and -2. These functionally caused an increase in monocyte adhesion to fibroblast monolayer. Using pharmacological intervention and BKR siRNA knockdown, we demonstrated that the BK-induced CXCL chemokine release, cell proliferation and COX and CAM expressions were mainly through the B2 receptor (B2R). Accordingly, the B2R was preferentially expressed in the NMDFs than B1R. The B2R was highly expressed in the CRSsNP than the control specimens, while the B1R and kininogen (KNG)/BK expression slightly increased in the CRSsNP mucosa. Collectively, we report here for the first time that fibroblasts, KNG/BK, and BKRs are overexpressed in CRSsNP mucosa and BK upregulates chemokine expression, proliferation, and proinflammatory molecule expression in NMDFs via B2R activation, which lead to a functional increase in monocyte-fibroblast interaction. Our findings reveal a critical role of fibroblast, KNG/BK, and BKRs in the development of CRSsNP.

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Primary role of growth‐related oncogene‐α and granulocyte chemotactic protein‐2 as neutrophil chemoattractants in chronic rhinosinusitis

Cited by 16 publications

References 24 publications

The Secretome Profiling of a Pediatric Airway Epithelium Infected with hRSV Identified Aberrant Apical/Basolateral Trafficking and Novel Immune Modulating (CXCL6, CXCL16, CSF3) and Antiviral (CEACAM1) Proteins

The Secretome Profiling of a Pediatric Airway Epithelium Infected with hRSV Identified Aberrant Apical/Basolateral Trafficking and Novel Immune Modulating (CXCL6, CXCL16, CSF3) and Antiviral (CEACAM1) Proteins

ORIGINAL ARTICLE: CXCL6 (Granulocyte Chemotactic Protein‐2): A Novel Chemokine Involved in the Innate Immune Response of the Amniotic Cavity

Involvement of B2 Receptor in Bradykinin-Induced Proliferation and Proinflammatory Effects in Human Nasal Mucosa-Derived Fibroblasts Isolated from Chronic Rhinosinusitis Patients

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