TY - JOUR
T1 - Metabolic Modulation of Cytokine-Induced Brain Endothelial Adhesion Molecule Expression
AU - Chaitanya, Ganta Vijay
AU - Cromer, Walter
AU - Wells, Shannon
AU - Jennings, Merilyn
AU - Mathis, James M.
AU - Minagar, Alireza
AU - Alexander, Jonathan Steven
PY - 2012/2/1
Y1 - 2012/2/1
N2 - Objective: Cytokines contribute to cerebro-vascular inflammatory and immune responses by inducing ECAMs' expression. Ischemic insults can be separated into aglycemic and hypoxic components. However, whether aglycemia, hypoxia or OGD plays a major role in dysregulating BBB or promotes immune cell infiltration via ECAMs' expression is not clear. We investigated how expression of ICAM-1, VCAM-1, MAdCAM-1, PECAM-1, E- and P-selectin in response to TNF-α, IL-1β and IFN-γ was altered by aglycemia (A), hypoxia (H) or combined oxygen glucose deprivation (OGD). Methods: A cell surface enzyme linked immunoabsorbent assay (cell surface ELISA) was used to analyze ECAM expression. Results: We observed that ICAM-1 and PECAM-1 expressions were insensitive to hypoxia, aglycemia or OGD. Conversely, VCAM-1 and E-selectin were increased by hypoxia, but not by aglycemia. MAdCAM-1 and P-selectin were induced by hypoxia, and decreased by aglycemia. Patterns of cytokine-regulated ECAMs' expression were also modified by metabolic conditions. Conclusions: Our results indicate that patterns of inflammation-associated ECAMs represent cumulative influences from metabolic stressors, as well as cytokine activation. The expression of ECAMs following tissue injury reflects mechanistic interactions between metabolic disturbances, and alterations in tissue cytokines. Normalization of tissue metabolism, as well as cytokine profiles, may provide important targets for therapeutic treatment of inflammation.
AB - Objective: Cytokines contribute to cerebro-vascular inflammatory and immune responses by inducing ECAMs' expression. Ischemic insults can be separated into aglycemic and hypoxic components. However, whether aglycemia, hypoxia or OGD plays a major role in dysregulating BBB or promotes immune cell infiltration via ECAMs' expression is not clear. We investigated how expression of ICAM-1, VCAM-1, MAdCAM-1, PECAM-1, E- and P-selectin in response to TNF-α, IL-1β and IFN-γ was altered by aglycemia (A), hypoxia (H) or combined oxygen glucose deprivation (OGD). Methods: A cell surface enzyme linked immunoabsorbent assay (cell surface ELISA) was used to analyze ECAM expression. Results: We observed that ICAM-1 and PECAM-1 expressions were insensitive to hypoxia, aglycemia or OGD. Conversely, VCAM-1 and E-selectin were increased by hypoxia, but not by aglycemia. MAdCAM-1 and P-selectin were induced by hypoxia, and decreased by aglycemia. Patterns of cytokine-regulated ECAMs' expression were also modified by metabolic conditions. Conclusions: Our results indicate that patterns of inflammation-associated ECAMs represent cumulative influences from metabolic stressors, as well as cytokine activation. The expression of ECAMs following tissue injury reflects mechanistic interactions between metabolic disturbances, and alterations in tissue cytokines. Normalization of tissue metabolism, as well as cytokine profiles, may provide important targets for therapeutic treatment of inflammation.
KW - Adhesion
KW - Endothelial
KW - Hypoxia
KW - Ischemia
KW - Reperfusion
UR - http://www.scopus.com/inward/record.url?scp=84856902265&partnerID=8YFLogxK
U2 - 10.1111/j.1549-8719.2011.00141.x
DO - 10.1111/j.1549-8719.2011.00141.x
M3 - Article
C2 - 21981016
AN - SCOPUS:84856902265
SN - 1073-9688
VL - 19
SP - 155
EP - 165
JO - Microcirculation
JF - Microcirculation
IS - 2
ER -