Differential cytokine responses in human and mouse lymphatic endothelial cells to cytokines in vitro

G. V. Chaitanya, S. E. Franks, W. Cromer, S. R. Wells, M. Bienkowska, M. H. Jennings, A. Ruddell, T. Ando, Y. Wang, Y. Gu, M. Sapp, J. M. Mathis, P. A. Jordan, A. Minagar, J. S. Alexander

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Abstract

Background: Inflammatory cytokines dysregulate microvascular function, yet how cytokines affect lymphatic endothelial cells (LEC) are unclear. Methods and Results: We examined effects of TNF-α, IL-1β, and IFN-γ on LEC proliferation, endothelial cell adhesion molecule (ECAM) expression, capillary formation, and barrier changes in murine (SV-LEC) and human LECs (HMEC-1a). Results: All cytokines induced ICAM-1, VCAM-1, MAdCAM-1, and E-selectin in SV-LECs; TNF-α, IL-1β and IFN-γ induced ECAMs (but not MAdCAM-1) in HMEC-1a. IL-1β increased, while IFN-γ and TNF-α reduced SV-LEC proliferation. While TNF-α induced, IFN-γ decreased, and IL-1β did not show any effect on HMEC-1a proliferation. TNF-α, IL-1β, and IFN-γ each reduced capillary formation in SV-LEC and in HMEC-1a. TNF-α and IL-1β reduced barrier in SV-LEC and HMEC-1a; IFN-γ did not affect SV-LEC barrier, but enhanced HMEC-1a barrier. Inflammatory cytokines alter LEC growth, activation and barrier function in vitro and may disturb lymphatic clearance increasing tissue edema in vivo. Conclusion: Therapies that maintain or restore lymphatic function (including cytokines blockade), may represent important strategies for limiting inflammation.

Original languageEnglish
Pages (from-to)155-164
Number of pages10
JournalLymphatic Research and Biology
Volume8
Issue number3
DOIs
StatePublished - 1 Sep 2010

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Chaitanya, G. V., Franks, S. E., Cromer, W., Wells, S. R., Bienkowska, M., Jennings, M. H., Ruddell, A., Ando, T., Wang, Y., Gu, Y., Sapp, M., Mathis, J. M., Jordan, P. A., Minagar, A., & Alexander, J. S. (2010). Differential cytokine responses in human and mouse lymphatic endothelial cells to cytokines in vitro. Lymphatic Research and Biology, 8(3), 155-164. https://doi.org/10.1089/lrb.2010.0004