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The effects of inflammatory cytokines on lymphatic endothelial barrier function

Content Provider	Springer Nature Link
Author	Cromer, Walter E. Zawieja, Scott D. Tharakan, Binu Childs, Ed W. Newell, M. Karen Zawieja, David C.
Copyright Year	2013
Abstract	Proper lymphatic function is necessary for the transport of fluids, macromolecules, antigens and immune cells out of the interstitium. The lymphatic endothelium plays important roles in the modulation of lymphatic contractile activity and lymph transport, but it’s role as a barrier between the lymph and interstitial compartments is less well understood. Alterations in lymphatic function have long been associated with edema and inflammation although the integrity of the lymphatic endothelial barrier during inflammation is not well-defined. In this paper we evaluated the integrity of the lymphatic barrier in response to inflammatory stimuli commonly associated with increased blood endothelial permeability. We utilized in vitro assays of lymphatic endothelial cell (LEC) monolayer barrier function after treatment with different inflammatory cytokines and signaling molecules including TNF-α, IL-6, IL-1β, IFN-γ and LPS. Moderate increases in an index of monolayer barrier dysfunction were noted with all treatments (20–60 % increase) except IFN-γ which caused a greater than 2.5-fold increase. Cytokine-induced barrier dysfunction was blocked or reduced by the addition of LNAME, except for IL-1β and LPS treatments, suggesting a regulatory role for nitric oxide. The decreased LEC barrier was associated with modulation of both intercellular adhesion and intracellular cytoskeletal activation. Cytokine treatments reduced the expression of VE-cadherin and increased scavenging of β-catenin in the LECs and this was partially reversed by LNAME. Likewise the phosphorylation of myosin light chain 20 at the regulatory serine 19 site, which accompanied the elevated monolayer barrier dysfunction in response to cytokine treatment, was also blunted by LNAME application. This suggests that the lymphatic barrier is regulated during inflammation and that certain inflammatory signals may induce large increases in permeability.
Starting Page	395
Ending Page	406
Page Count	12
File Format	PDF
ISSN	09696970
Journal	Angiogenesis
Volume Number	17
Issue Number	2
e-ISSN	15737209
Language	English
Publisher	Springer Netherlands
Publisher Date	2013-10-20
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Lymphatic Endothelial Permeability Cytokines Barrier Cancer Research Biomedicine general Cell Biology Cardiology Ophthalmology Oncology
Content Type	Text
Resource Type	Article
Subject	Physiology Clinical Biochemistry Cancer Research

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