Potential protective role of IL15Rα during inflammation.
We have shown that TNFα specifically activates the interleukin-15 (IL15) system in cerebral endothelial cells composing the blood-brain barrier. To determine the functions of cerebral IL15 signaling in inflammation, we first treated mice with lipopolysaccharide (LPS) and determined the expression of the three receptor subtypes of IL15. Robust time-dependent upregulation occurred in all subunits. We then tested whether IL15Rα knockout (KO) affected the maintenance of body temperature and activity level after a single dose of LPS. Circadian telemetry data were analyzed by the cosinor method. Both wild-type and KO mice had clear 24-h rhythms of basal temperature and activity. KO mice had a significantly higher midline estimating statistic of rhythm (MESOR; approximating 24 h mean) of temperature and delayed 24-h acrophase (peak) of activity than the wild-type mice. LPS disrupted the circadian rhythm of activity more severely in the KO group. Besides a decrease in MESOR and 24-h amplitude of activity after LPS, the KO mice showed a significant reduction of MESOR, amplitude, and changed acrophase for temperature on the second of 2 days. The disrupted circadian rhythm of temperature and activity in the KO mice after LPS suggests that upregulated IL15 receptors may serve a beneficial role to counteract the consequences of neuroinflammation.
Pan
Weihong
W
Blood-Brain Barrier Group, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USA. weihong.pan@pbrc.edu
Wu
Xiaojun
X
Kastin
Abba J
AJ
Zhang
Yan
Y
Hsuchou
Hung
H
Halberg
Franz
F
Chatu
Finla
F
Khan
Reas S
RS
Robert
Barry
B
Cornelissen-Guillaume
Germaine G
GG
D000818:Animals; D001831:Body Temperature / Q000502:physiology; D002490:Central Nervous System / Q000033:anatomy & histology / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology; D007249:Inflammation / Q000276:immunology*; D053720:Interleukin-15 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology*; D013686:Telemetry
D053720:Interleukin-15 Receptor alpha Subunit; D008070:Lipopolysaccharides; D020033:Protein Isoforms