TY - JOUR
T1 - Differential cytokine responses in human and mouse lymphatic endothelial cells to cytokines in vitro
AU - Chaitanya, G. V.
AU - Franks, S. E.
AU - Cromer, W.
AU - Wells, S. R.
AU - Bienkowska, M.
AU - Jennings, M. H.
AU - Ruddell, A.
AU - Ando, T.
AU - Wang, Y.
AU - Gu, Y.
AU - Sapp, M.
AU - Mathis, J. M.
AU - Jordan, P. A.
AU - Minagar, A.
AU - Alexander, J. S.
PY - 2010/9/1
Y1 - 2010/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77957571628&partnerID=8YFLogxK
U2 - 10.1089/lrb.2010.0004
DO - 10.1089/lrb.2010.0004
M3 - Article
C2 - 20863268
AN - SCOPUS:77957571628
SN - 1539-6851
VL - 8
SP - 155
EP - 164
JO - Lymphatic Research and Biology
JF - Lymphatic Research and Biology
IS - 3
ER -