Inter-alpha inhibitor proteins attenuate lipopolysaccharide-induced blood-brain barrier disruption and downregulate circulating interleukin 6 in mice.
|
| Abstract |
Circulating levels of inter-alpha inhibitor proteins change dramatically in acute inflammatory disorders, which suggest an important contribution to the immunomodulatory system. Human blood-derived inter-alpha inhibitor proteins are neuroprotective and improve survival of neonatal mice exposed to lipopolysaccharide. Lipopolysaccharide augments inflammatory conditions and disrupts the blood-brain barrier. There is a paucity of therapeutic strategies to treat blood-brain barrier dysfunction, and the neuroprotective effects of human blood-derived inter-alpha inhibitor proteins are not fully understood. To examine the therapeutic potential of inter-alpha inhibitor proteins, we administered human blood-derived inter-alpha inhibitor proteins to male and female CD-1 mice after lipopolysaccharide exposure and quantified blood-brain barrier permeability of intravenously injected 14C-sucrose and 99mTc-albumin. We hypothesized that human blood-derived inter-alpha inhibitor protein treatment would attenuate lipopolysaccharide-induced blood-brain barrier disruption and associated inflammation. Lipopolysaccharide increased blood-brain barrier permeability to both 14C-sucrose and 99mTc-albumin, but human blood-derived inter-alpha inhibitor protein treatment only attenuated increases in 14C-sucrose blood-brain barrier permeability in male mice. Lipopolysaccharide stimulated a more robust elevation of male serum inter-alpha inhibitor protein concentration compared to the elevation measured in female serum. Lipopolysaccharide administration also increased multiple inflammatory factors in serum and brain tissue, including interleukin 6. Human blood-derived inter-alpha inhibitor protein treatment downregulated serum interleukin 6 levels, which were inversely correlated with serum inter-alpha inhibitor protein concentration. We conclude that inter-alpha inhibitor proteins may be neuroprotective through mechanisms of blood-brain barrier disruption associated with systemic inflammation.
|
|---|---|
| Authors | Aric F Logsdon, Michelle A Erickson, Xiaodi Chen, Joseph Qiu, Yow-Pin Lim, Barbara S Stonestreet, William A Banks |
| Journal | Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 40 Issue 5 Pg. 1090-1102 (05 2020) ISSN: 1559-7016 [Electronic] United States |
| PMID | 31234704 (Publication Type: Journal Article, Research Support, N.I.H., Extramural) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!