Transcriptional Mechanisms Regulating Alveolar Epithelial Cell-specific CCL5 Secretion in Pulmonary Tuberculosis

Wickremasinghe, Melissa; Thomas, Lynette H.; O'Kane, Cecilia M; Uddin, Jasim; Friedland, Jon S.

doi:10.1074/jbc.m403107200

Cited by 79 publications

(54 citation statements)

References 67 publications

(74 reference statements)

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“…5 and data not shown). Binding sites for IRF-3 and classical NF-B dimers, such as RelA:p50 implicated in the induction of inflammatory chemokines, or binding sites for nonclassical NF-B dimers RelB:p52, implicated in driving homeostatic chemokine gene expression (7,(37)(38)(39)(40)(41)(42)(43)(44)(45), were not detected within a region covering Ϫ2000 to ϩ25 bp of the CCL25 promoter, supporting the notion that these factors are not directly involved in the regulation of CCL25 expression.…”

Section: The Ccl25 Promoter Contains Putative Binding Sites For CDX Tmentioning

confidence: 63%

Functional Characterization of the CCL25 Promoter in Small Intestinal Epithelial Cells Suggests a Regulatory Role for Caudal-Related Homeobox (Cdx) Transcription Factors

Ericsson¹,

Kotarsky²,

Svensson³

et al. 2006

The Journal of Immunology

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The chemokine CCL25 is selectively and constitutively expressed in the small intestinal epithelium and plays an important role in mediating lymphocyte recruitment to this site. In this study, we demonstrate that CCL25 expression in murine small intestinal epithelial cells is independent of signaling through the lymphotoxin β receptor and is not enhanced by inflammatory stimuli, pathways involved in driving the expression of most other chemokines. We define a transcriptional start site in the CCL25 gene and a region −141 to −5 proximal of exon 1 that is required for minimal promoter activity in the small intestinal epithelial cell lines, MODE-K and mICc12. These cell lines expressed far less CCL25 mRNA than freshly isolated small intestinal epithelial cells indicating that they are missing important factors driving CCL25 expression. The CCL25 promoter contained putative binding sites for the intestinal epithelial-associated Caudal-related homeobox (Cdx) transcription factors Cdx-1 and Cdx-2, and small intestinal epithelial cells but not MODE-K and mICc12 cells expressed Cdx-1 and Cdx-2. EMSA analysis demonstrated that Cdx proteins were present in nuclear extracts from freshly isolated small intestinal epithelial cells but not in MODE-K or mICcl2 cells, and bound to putative Cdx sites within the CCL25 promoter. Finally, cotransfection of MODE-K cells with Cdx transcription factors significantly increased CCL25 promoter activity as well as endogenous CCL25 mRNA levels. Together these results demonstrate a unique pattern of regulation for CCL25 and suggest a role for Cdx proteins in regulating CCL25 transcription.

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Section: The Ccl25 Promoter Contains Putative Binding Sites For CDX Tmentioning

confidence: 63%

Functional Characterization of the CCL25 Promoter in Small Intestinal Epithelial Cells Suggests a Regulatory Role for Caudal-Related Homeobox (Cdx) Transcription Factors

Ericsson¹,

Kotarsky²,

Svensson³

et al. 2006

The Journal of Immunology

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“…These data are supported by previous studies showing that mitogen-activated protein kinase and NF-κB signaling pathways modulate the release of chemokines and cytokines. [38][39][40][41][42] In conclusion, our study provides the first evidence of a novel phenomenon, whereby cross talk between CD11b + Gr1 + neutrophils and CFs amplifies the proinflammatory response via S100a8/a9 secretion. The mechanisms by which Ang IIinduced hypertensive microenvironment activated CD11b + Gr1 + neutrophils to produce S100a8/a9 remain to be established, and our study should stimulate further studies aimed at addressing this important question.…”

Section: Downloaded Frommentioning

confidence: 91%

S100a8/a9 Released by CD11b ⁺ Gr1 ⁺ Neutrophils Activates Cardiac Fibroblasts to Initiate Angiotensin II–Induced Cardiac Inflammation and Injury

Li²,

Zhang³

et al. 2014

Hypertension

107

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+ Gr1+ neutrophils in the heart. The receptor for advanced glycation end products, an S100a8/ a9 receptor, was expressed in cardiac fibroblasts (CFs). Microarray analysis and Bio-Plex protein array showed that treatment of CFs with recombinant S100a8/a9 activated multiple chemokine and cytokines released. Luciferase reporter assay indicated S100a8/a9-activated nuclear factor-κ B pathway in CFs. Consequently, recombinant S100a8/a9-treated CFs promoted migration of monocytes and CFs, whereas neutralizing S100a9 antibody blocked S100a9 or receptor for advanced glycation end products-suppressed cellular migration. Finally, administration of a neutralizing S100a9 antibody prevented angiotensin II infusion-induced nuclear factor-κ B activation, inflammatory cell infiltration, cytokine production, subsequent perivascular and interstitial fibrosis, and hypertrophy in heart. Our findings identify neutrophilproduced S100a8/a9 as an initial proinflammatory factor needed to trigger inflammation and cardiac injury during acute

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“…7D). To ascertain whether this effect was specific, we tested the effect of CXCL12, another CXC chemokine secreted in high quantities by activated fibroblasts (40), and CCL5, which is also secreted by pulmonary fibroblasts (41) and is known to be upregulated in the host response to Mtb (30), on the intracellular growth of mycobacteria. Neither had any significant effect (data not shown).…”

Section: Cxcl8 Limits the Intracellular Growth Of Mtb In Macrophages mentioning

confidence: 99%

“…Western blotting for IB␣/IB␤ and total/phosphorylated p38 detection was conducted as previously described (30).…”

Section: Western Blottingmentioning

confidence: 99%

Monocyte-Dependent Fibroblast CXCL8 Secretion Occurs in Tuberculosis and Limits Survival of Mycobacteria within Macrophages

O’Kane

Boyle

Horncastle

et al. 2007

The Journal of Immunology

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CXCL8 is a chemokine that is implicated in the formation of tuberculous (TB) granulomas and in immunity to Mycobacterium tuberculosis (Mtb). Fibroblast chemokine secretion is important for modulating inflammatory responses in chronic lung disease and inflammatory arthritis but has not been investigated in the pathophysiology of TB. In this study, we used a cellular model to examine monocyte/macrophage-dependent stimulation of fibroblasts by Mtb in the regulation of chemokine secretion, particularly that of CXCL8. Human lung fibroblasts grown in collagen were stimulated with conditioned medium from Mtb-infected monocytes (CoMTb). CoMTb-induced prolonged dose-dependent, p38-mediated expression of stable CXCL8 mRNA by fibroblasts accompanied by a >10-fold increase in CXCL8 secretion (487 ± 88 ng/ml vs 48.6 ± 34 ng/ml in controls) at 120 h. Fibroblasts strongly expressed CXCL8 in vivo in human TB granulomas. Inhibition of TNF-α or IL-1 in CoMTb abrogated the induction of CXCL8 at a pretranscriptional level. CXCL8 secretion was NF-κB, C/EBP, and JNK dependent. Sustained NF-κB activation was demonstrated beyond 24 h in response to CoMTb. Exogenous CXCL8 reduced the survival of Mtb within macrophages, and inhibition of CXCL8 was associated with intracellular mycobacterial proliferation. These data show that fibroblasts have a previously unrecognized role in modulating inflammation in TB by their CXCL8-dependent contribution to cell recruitment and mycobacterial killing within the granuloma.

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Transcriptional Mechanisms Regulating Alveolar Epithelial Cell-specific CCL5 Secretion in Pulmonary Tuberculosis

Abstract: CCL5 (or RANTES(

Cited by 79 publications

References 67 publications

Functional Characterization of the CCL25 Promoter in Small Intestinal Epithelial Cells Suggests a Regulatory Role for Caudal-Related Homeobox (Cdx) Transcription Factors

Functional Characterization of the CCL25 Promoter in Small Intestinal Epithelial Cells Suggests a Regulatory Role for Caudal-Related Homeobox (Cdx) Transcription Factors

S100a8/a9 Released by CD11b ⁺ Gr1 ⁺ Neutrophils Activates Cardiac Fibroblasts to Initiate Angiotensin II–Induced Cardiac Inflammation and Injury

Monocyte-Dependent Fibroblast CXCL8 Secretion Occurs in Tuberculosis and Limits Survival of Mycobacteria within Macrophages

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Transcriptional Mechanisms Regulating Alveolar Epithelial Cell-specific CCL5 Secretion in Pulmonary Tuberculosis

Abstract: CCL5 (or RANTES(

Cited by 79 publications

References 67 publications

Functional Characterization of the CCL25 Promoter in Small Intestinal Epithelial Cells Suggests a Regulatory Role for Caudal-Related Homeobox (Cdx) Transcription Factors

Functional Characterization of the CCL25 Promoter in Small Intestinal Epithelial Cells Suggests a Regulatory Role for Caudal-Related Homeobox (Cdx) Transcription Factors

S100a8/a9 Released by CD11b + Gr1 + Neutrophils Activates Cardiac Fibroblasts to Initiate Angiotensin II–Induced Cardiac Inflammation and Injury

Monocyte-Dependent Fibroblast CXCL8 Secretion Occurs in Tuberculosis and Limits Survival of Mycobacteria within Macrophages

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S100a8/a9 Released by CD11b ⁺ Gr1 ⁺ Neutrophils Activates Cardiac Fibroblasts to Initiate Angiotensin II–Induced Cardiac Inflammation and Injury