Experimental ileitis alters prostaglandin biosynthesis in mesenteric lymphatic and blood vessels

Rehal, Sonia; Weid, Pierre‐Yves von der

doi:10.1016/j.prostaglandins.2014.11.001

Cited by 16 publications

(15 citation statements)

References 59 publications

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“…Unlike the involvement of COXs in impaired lymphatic pumping during intestinal inflammation demonstrated by Wu et al . [77] and Rehal & von der Weid [56], we observed no restoration of lymphatic pumping by indomethacin and no significant changes in COX-1 and COX-2 mRNA expression in TNF-α -treated vessels at least up to 24 h after treatment. These results are surprising because COX-2 is usually upregulated by TNF-α via the NF-κB pathway [5,79], as well as other pathways [31], but may suggest difference in qualitative or temporal gene regulation in different tissues or cell types.…”

Section: Discussioncontrasting

confidence: 44%

“…Experimental ileitis was induced in rats as published previously [56]. Briefly, rats were fasted for 4–6 h and prepared for anaesthesia (4% isofluorane induction, maintained at 2% throughout the procedure).…”

Section: Methodsmentioning

confidence: 99%

“…Animals were euthanized 3 days after surgery by inhalation of an overdose of isofluorane followed by decapitation as described above. Severity of inflammation was assessed using three parameters: macroscopic damage score, weight loss and myeloperoxidase (MPO) activity as published previously [56], and mesenteric lymphatic vessels draining the inflamed site isolated.…”

Section: Methodsmentioning

confidence: 99%

“…Experimental ileitis was induced in rats as published previously. 17 Briefly, rats were fasted for 4-6 hours and prepared for anesthesia (4% isoflurane induction, maintained at 2% throughout the procedure). A surgical laparotomy was performed under sterile conditions to allow a segment of the ileum, 10 cm proximal to the ileocecal junction to be exteriorized.…”

Section: Surgical Induction Of Ileitismentioning

confidence: 99%

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The pro‐inflammatory cytokineTNF‐α inhibits lymphatic pumping via activation of theNF‐κB‐iNOSsignaling pathway

et al. 2017

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Objective Mesenteric lymphatic vessels pumping, important to propel lymph and immune cells from the intestinal interstitium to the mesenteric lymph nodes, is compromised during intestinal inflammation. The objective of this study was to test the hypothesis that the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α), is a significant contributor to the inflammation-induced lymphatic contractile dysfunction, and to determine its mode of action. Methods Contractile parameters were obtained form isolated rat mesenteric lymphatic vessels mounted on a pressure myograph after 24-h incubation with or without TNF-α. Various inhibitors were administered and quantitative real-time PCR, western blotting and immunofluorescence confocal imaging were applied to characterize the mechanisms involved in TNF-α actions. Results Vessel contraction frequency was significantly decreased after TNF-α treatment and could be restored by selective inhibition of NF-кB, iNOS, guanylate cyclase and ATP-sensitive K+ channels. We further demonstrated that NF-кB inhibition also suppressed the significant increase in iNOS mRNA observed in TNF-α-treated lymphatic vessels and that TNF-α treatment favor the nuclear translocation of the p65 NF-κB subunit. Conclusions These findings suggest that TNF-α decreases mesenteric lymphatic contractility by activating the NF-κB - iNOS signaling pathway. This mechanism could contribute to the alteration of lymphatic pumping reported in intestinal inflammation.

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Section: Discussioncontrasting

confidence: 44%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Surgical Induction Of Ileitismentioning

confidence: 99%

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The pro‐inflammatory cytokineTNF‐α inhibits lymphatic pumping via activation of theNF‐κB‐iNOSsignaling pathway

et al. 2017

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“…Differences in weight were measured as percent weight loss pre-and post-DSS/ sham treatment. Myeloperoxidase (MPO) activity was measured in terminal ileum as previously published (53). For histological assessment, swiss-rolled small intestines were fixed in neutral-buffered formalin, embedded in paraffin, sectioned, and stained with hematoxylin and eosin (H&E) and then examined by light microscopy (Dmi1 Stereomicroscope; Leica Microsystems Concord, ON, Canada).…”

Section: Assessment Of Inflammationmentioning

confidence: 99%

Acute small intestinal inflammation results in persistent lymphatic alterations

Rehal

Stephens

Roizes

et al. 2018

American Journal of Physiology-Gastrointestinal and Liver Physi

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Inflammatory bowel disease (IBD) has a complex pathophysiology with limited treatments. Structural and functional changes in the intestinal lymphatic system have been associated with the disease, with increased risk of IBD occurrence linked to a history of acute intestinal injury. To examine the potential role of the lymphatic system in inflammation recurrence, we evaluated morphological and functional changes in mouse mucosal and mesenteric lymphatic vessels, and within the mesenteric lymph nodes during acute ileitis caused by a 7-day treatment with dextran sodium sulfate (DSS). We monitored whether the changes persisted during a 14-day recovery period and determined their potential consequences on dendritic cell (DC) trafficking between the mucosa and lymphoid tissues. DSS administration was associated with marked lymphatic abnormalities and dysfunctions exemplified by lymphangiectasia and lymphangiogenesis in the ileal mucosa and mesentery, increased mesenteric lymphatic vessel leakage, and lymphadenopathy. Lymphangiogenesis and lymphadenopathy were still evident after recovery from intestinal inflammation and correlated with higher numbers of DCs in mucosal and lymphatic tissues. Specifically, a deficit in CD103 DCs observed during acute DSS in the lamina propria was reversed and further enhanced during recovery. We concluded that an acute intestinal insult caused alterations of the mesenteric lymphatic system, including lymphangiogenesis, which persisted after resolution of inflammation. These morphological and functional changes could compromise DC function and movement, increasing susceptibility to further gastrointestinal disease. Elucidation of the changes in mesenteric and intestinal lymphatic function should offer key insights for new therapeutic strategies in gastrointestinal disorders such as IBD. NEW & NOTEWORTHY Lymphatic integrity plays a critical role in small intestinal homeostasis. Acute intestinal insult in a mouse model of acute ileitis causes morphological and functional changes in mesenteric and intestinal lymphatic vessels. While some of the changes significantly regressed during inflammation resolution, others persisted, including lymphangiogenesis and altered dendritic cell function and movement, potentially increasing susceptibility to the recurrence of gastrointestinal inflammation.

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TNFΔARE Mice Display Abnormal Lymphatics and Develop Tertiary Lymphoid Organs in the Mesentery

Rehal

Weid

2017

The American Journal of Pathology

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Chronic inflammatory diseases are associated with a persistent and enhanced response to environmental antigens. As an adaptive response to this exaggerated immune state, affected tissue typically develops tertiary lymphoid organs. Studies of Crohn disease (CD), a chronic inflammatory disease of the intestinal tract, report tertiary lymphoid organs present within the mucosal wall, along with other lymphatic diseases, such as lymphangiogenesis and obstructed lymphatic vessels. These observations suggest that downstream mesenteric lymphatic vessels and lymph drainage into mesenteric lymph nodes may be compromised. However, information is lacking on the morphologic features and functional status of mesenteric lymphatics in CD. Using confocal imaging, PCR, flow cytometry, and functional strategies, we addressed these questions in the established TNFΔARE mouse model of CD and found that this mouse model had many lymphatic abnormalities reminiscent of human CD. These abnormalities include intestinal lymphangiectasia, mesenteric lymph node lymphadenopathy, and lymphangiogenesis in both the mesentery and mucosa. Critically, TNFΔARE mice also present mesenteric tertiary lymphoid organs and have altered lymphatic transport of dendritic cells to mesenteric lymph nodes, two features likely to actively modulate immunity. Our findings provide key insights into lymphatic remodeling in the TNFΔARE mouse model. They shed light on the involvement of these lymphatic changes in immune dysfunctions observed in CD and suggest the lymphatic system as new target for therapeutic options.

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Experimental ileitis alters prostaglandin biosynthesis in mesenteric lymphatic and blood vessels

Cited by 16 publications

References 59 publications

The pro‐inflammatory cytokineTNF‐α inhibits lymphatic pumping via activation of theNF‐κB‐iNOSsignaling pathway

The pro‐inflammatory cytokineTNF‐α inhibits lymphatic pumping via activation of theNF‐κB‐iNOSsignaling pathway

Acute small intestinal inflammation results in persistent lymphatic alterations

TNFΔARE Mice Display Abnormal Lymphatics and Develop Tertiary Lymphoid Organs in the Mesentery

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