Metabolic Modulation of Cytokine-Induced Brain Endothelial Adhesion Molecule Expression

Ganta Vijay Chaitanya, Walter Cromer, Shannon Wells, Merilyn Jennings, James M. Mathis, Alireza Minagar, Jonathan Steven Alexander

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15 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)155-165
Number of pages11
JournalMicrocirculation
Volume19
Issue number2
DOIs
StatePublished - 1 Feb 2012

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Keywords

  • Adhesion
  • Endothelial
  • Hypoxia
  • Ischemia
  • Reperfusion

Cite this

Chaitanya, G. V., Cromer, W., Wells, S., Jennings, M., Mathis, J. M., Minagar, A., & Alexander, J. S. (2012). Metabolic Modulation of Cytokine-Induced Brain Endothelial Adhesion Molecule Expression. Microcirculation, 19(2), 155-165. https://doi.org/10.1111/j.1549-8719.2011.00141.x