Lymphatic Endothelial Cells, Inflammatory Lymphangiogenesis, and Prospective Players

Rc, Ji

doi:10.2174/092986707781745541

Cited by 41 publications

(38 citation statements)

References 115 publications

(153 reference statements)

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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%

“…Lymphatic endothelial cells (LECs) at a site of inflammation have been shown to actively participate in and regulate inflammatory processes and host immune responses, thereby emerging as major players in progression and resolution of the inflammatory state (18,19,46,47,50,64). Since inflammation acts as a primary trigger for pathological lymphangiogenesis, a number of proinflammatory cytokines have also been shown to function as prolymphangiogenic factors (15,25,49).…”

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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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“…LECs may, additionally, undergo similar cellular processes like proliferation, differentiation, and formation of new networks. In the past decade, lymphangiogenesis including its molecular and functional characteristics, and macrophages including their alternative activation in tumor and inflammation have been reviewed separately [9,[12][13][14][15]. The role of macrophages in the formation of new initial lymphatics remains to be elucidated.…”

Section: Bmdcsmentioning

confidence: 99%

Macrophages are important mediators of either tumor- or inflammation-induced lymphangiogenesis

2011

Cell. Mol. Life Sci.

113

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The lymphatic system provides important functions for tissue fluid homeostasis and immune response. Lymphangiogenesis, the formation of new lymphatics, comprises a series of complex cellular events in vitro or in vivo, e.g., proliferation, differentiation, and sprouting. Recent evidence has implied that macrophages act as a direct structural contributor to lymphatic endothelial walls or secret VEGF-C/-D and VEGF-A to initiate lymphangiogenesis in inflamed or tumor tissues. Bone marrow-derived macrophages are versatile cells that express different functional programs in response to exposure to microenvironmental signals, and can be identified by specific expression of a number of proteins, F4/80, CD11b, and CD68. Several causative factors, e.g., NF-κB, IL-1β, TNF-α, SDF-1, M-CSF, especially TonEBP/VEGF-C signaling, may be actively involved in macrophage-induced lymphangiogenesis. Alteration of macrophage phenotype and function has a profound effect on the development and progression of inflammation and malignancy, and macrophage depletion for controlling lymphangiogenesis may provide a novel approach for prevention and treatment of lymphatic-associated diseases.

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“…Adult lymphangiogenesis occurs during inflammation and wound healing [1,10], but is also strongly associated with chronic inflammation, autoimmunity, and allograft rejection [11][12][13][14][15][16] as well as with tumor invasion and metastasis when initiated both around the tumor and in the draining LN [17][18][19][20][21]. These are all associated with different immunological outcomes: from Th1 and Th2 inflammatory responses to immune escape and tolerance.…”

Section: Introductionmentioning

confidence: 99%

Role of Lymphatic Vessels in Tumor Immunity: Passive Conduits or Active Participants?

Lund

Swartz

2010

J Mammary Gland Biol Neoplasia

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Research in lymphatic biology and cancer immunology may soon intersect as emerging evidence implicates the lymphatics in the progression of chronic inflammation and autoimmunity as well as in tumor metastasis and immune escape. Like the blood vasculature, the lymphatic system comprises a highly dynamic conduit system that regulates fluid homeostasis, antigen transport and immune cell trafficking, which all play important roles in the progression and resolution of inflammation, autoimmune diseases, and cancer. This review presents emerging evidence that lymphatic vessels are active modulators of immunity, perhaps fine-tuning the response to adjust the balance between peripheral tolerance and immunity. This suggests that the tumor-associated lymphatic vessels and draining lymph node may be important in tumor immunity which in turn governs metastasis.

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Lymphatic Endothelial Cells, Inflammatory Lymphangiogenesis, and Prospective Players

Cited by 41 publications

References 115 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

Macrophages are important mediators of either tumor- or inflammation-induced lymphangiogenesis

Role of Lymphatic Vessels in Tumor Immunity: Passive Conduits or Active Participants?

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