Differential Cytokine Responses in Human and Mouse Lymphatic Endothelial Cells to Cytokines<i>in Vitro</i>

Chaitanya, Ganta Vijay; Franks, Samuel Eugene; Cromer, Walter; Wells, Shannon; Bieńkowska, M; Jennings, Merilyn H.; Ruddell, Alanna; Ando, Tomoaki; Wang, Y.; Gu, Yang; Sapp, Martin; Mathis, J. Michael; Jordan, Paul; Minagar, Alireza; Alexander, J. Steven

doi:10.1089/lrb.2010.0004

Cited by 51 publications

(52 citation statements)

References 71 publications

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“…Although several studies have shown the close association of inflammation and lymphangiogenesis (19,46,47,64), the role of the proinflammatory cytokine TNF-␣ in modulating lymphangiogenesis remains controversial (4,6,22,48). Since miR-9 was upregulated in the TNF-␣-treated LECs and it also directly targets NF-B, we assessed the effects of miR-9 in LECs on lymphatic tube formation.…”

Section: Mir-9 Inhibits Nf-b Signaling In Lecs But Promotes Lymphaticmentioning

confidence: 99%

“…LECs, in turn, respond to inflammatory cytokines by upregulating chemokines, adhesion molecules, and other cytokines, indicating that LECs are also affected by the local inflammatory milieu at sites of infection or vaccination (44). Although a large number of these molecules expressed by inflamed LECs have been described (6,54,55), a critical group of potential regulators of the inflammatory mechanisms, specifically the microRNAs (miRNAs), remain completely unexplored in the lymphatic system. miRNAs are a recently recognized class of highly conserved, noncoding short (18 -22 nucleotides) RNA molecules that regulate gene expression at the posttranscriptional level (27).…”

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confidence: 99%

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MicroRNA signature of inflamed lymphatic endothelium and role of miR-9 in lymphangiogenesis and inflammation

Chakraborty

Zawieja

Davis

et al. 2015

American Journal of Physiology-Cell Physiology

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Chakraborty S, Zawieja DC, Davis MJ, Muthuchamy M. MicroRNA signature of inflamed lymphatic endothelium and role of miR-9 in lymphangiogenesis and inflammation. Am J Physiol Cell Physiol 309: C680 -C692, 2015. First published September 9, 2015; doi:10.1152/ajpcell.00122.2015.-The lymphatics have emerged as critical players in the progression and resolution of inflammation. The goal of this study was to identify specific microRNAs (miRNAs) that regulate lymphatic inflammatory processes. Rat mesenteric lymphatic endothelial cells (LECs) were exposed to the proinflammatory cytokine tumor necrosis factor-␣ for 2, 24, and 96 h, and miRNA profiling was carried out by real-time PCR arrays. Our data demonstrate a specific set of miRNAs that are differentially expressed (Ͼ1.8-fold and/or P Ͻ 0.05) in LECs in response to tumor necrosis factor-␣ and are involved in inflammation, angiogenesis, endothelial-mesenchymal transition, and cell proliferation and senescence. We further characterized the expression of miRNA 9 (miR-9) that was induced in LECs and in inflamed rat mesenteric lymphatics. Our results showed that miR-9 overexpression significantly repressed NF-B expression and, thereby, suppressed inflammation but promoted LEC tube formation, as well as expression of the prolymphangiogenic molecules endothelial nitric oxide synthase and VEGF receptor type 3. LEC viability and proliferation and endothelial-mesenchymal transition were also significantly induced by miR-9. This study provides the first evidence of a distinct profile of miRNAs associated with LECs during inflammation. It also identifies the critical dual role of miR-9 in fine-tuning the balance between lymphatic inflammatory and lymphangiogenic pathways.

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Section: Mir-9 Inhibits Nf-b Signaling In Lecs But Promotes Lymphaticmentioning

confidence: 99%

mentioning

confidence: 99%

MicroRNA signature of inflamed lymphatic endothelium and role of miR-9 in lymphangiogenesis and inflammation

Chakraborty

Zawieja

Davis

et al. 2015

American Journal of Physiology-Cell Physiology

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“…TNF has been reported to impair capillary tube formation and barrier function in mouse and human LECs. 23 Intradermal administration of TNF in mice also results in an acute and systemic deterioration of lymphatic propulsion. 24 In addition, hTNFtg mice, a model of chronic inflammatory arthritis, exhibit decreased lymph flow from the joints compared with wild-type littermates.…”

Section: Discussionmentioning

confidence: 99%

Apolipoprotein A-I Limits the Negative Effect of Tumor Necrosis Factor on Lymphangiogenesis

Bisoendial

Tabet

Tak

et al. 2015

ATVB

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Objective— Lymphatic endothelial dysfunction underlies the pathogenesis of many chronic inflammatory disorders. The proinflammatory cytokine tumor necrosis factor (TNF) is known for its role in disrupting the function of the lymphatic vasculature. This study investigates the ability of apolipoprotein (apo) A-I, the principal apolipoprotein of high-density lipoproteins, to preserve the normal function of lymphatic endothelial cells treated with TNF. Approach and Results— TNF decreased the ability of lymphatic endothelial cells to form tube-like structures. Preincubation of lymphatic endothelial cells with apoA-I attenuated the TNF-mediated inhibition of tube formation in a concentration-dependent manner. In addition, apoA-I reversed the TNF-mediated suppression of lymphatic endothelial cell migration and lymphatic outgrowth in thoracic duct rings. ApoA-I also abrogated the negative effect of TNF on lymphatic neovascularization in an ATP-binding cassette transporter A1-dependent manner. At the molecular level, this involved downregulation of TNF receptor-1 and the conservation of prospero-related homeobox gene-1 expression, a master regulator of lymphangiogenesis. ApoA-I also re-established the normal phenotype of the lymphatic network in the diaphragms of human TNF transgenic mice. Conclusions— ApoA-I restores the neovascularization capacity of the lymphatic system during TNF-mediated inflammation. This study provides a proof-of-concept that high-density lipoprotein–based therapeutic strategies may attenuate chronic inflammation via its action on lymphatic vasculature.

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“…Expression of MAdCAM-1 is regulated by the NF-kB and PI3K/AKT signaling pathways [18][19][20][21], both of which strongly correlate with the inflammatory response. Indeed, treatments with a variety of proinflammatory molecules, including lipopolysaccharide, TNF-a, IL-1b, IFN-g, and CXCL12 [18,19,[21][22][23], can enhance MAdCAM-1 expression in EC cell lines. However, it is unknown whether endothelial MAdCAM-1 expression within the BM microenvironment is regulated by similar molecular mechanisms.…”

Section: Blocking Madcam-1 Reduces the Homing Of Hscs To The Bm And Smentioning

confidence: 99%

Evidence that β7 Integrin Regulates Hematopoietic Stem Cell Homing and Engraftment Through Interaction with MAdCAM-1

Murakami

Franco

et al. 2016

Stem Cells and Development

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a4b7 integrin is a cell adhesion receptor that is crucial for the migration of hematopoietic progenitors and mature effector cells in the periphery, but its role in adult hematopoiesis is controversial. We identified a subset of hematopoietic stem cells (HSCs) in the bone marrow (BM) that expressed b7 integrin. These b7 + HSCs were capable of multilineage, long-term reconstitution and had an inherent competitive advantage over b7 -HSCs. On the other hand, HSCs that lacked b7 integrin (b7KO) had reduced engraftment potential. Interestingly, quantitative RT-PCR and flow cytometry revealed that b7KO HSCs expressed lower levels of the chemokine receptor CXCR4. Accordingly, b7KO HSCs exhibited impaired migration abilities in vitro and BM homing capabilities in vivo. Lethal irradiation induced expression of the a4b7 integrin ligand-mucosal addressin cell adhesion molecule-1 (MAdCAM-1) on BM endothelial cells. Moreover, blocking MAdCAM-1 reduced the homing of HSCs and impaired the survival of recipient mice. Altogether, these data indicate that b7 integrin, when expressed by HSCs, interacted with its endothelial ligand MAdCAM-1 in the BM microenvironment, thereby promoting HSC homing and engraftment.

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Differential Cytokine Responses in Human and Mouse Lymphatic Endothelial Cells to Cytokinesin Vitro

Cited by 51 publications

References 71 publications

MicroRNA signature of inflamed lymphatic endothelium and role of miR-9 in lymphangiogenesis and inflammation

MicroRNA signature of inflamed lymphatic endothelium and role of miR-9 in lymphangiogenesis and inflammation

Apolipoprotein A-I Limits the Negative Effect of Tumor Necrosis Factor on Lymphangiogenesis

Evidence that β7 Integrin Regulates Hematopoietic Stem Cell Homing and Engraftment Through Interaction with MAdCAM-1

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