title: Time-dependent effects of localized inflammation on peripheral clock gene expression in rats.
abstract: Many aspects of the immune system, including circulating cytokine levels as well as counts and function of various immune cell types, present circadian rhythms. Notably, the mortality rate of animals subjected to high doses of lipopolysaccharide is dependent on the time of treatment. In addition, the severity of symptoms of various inflammatory conditions follows a daily rhythmic pattern. The mechanisms behind the crosstalk between the circadian and immune systems remain elusive. Here we demonstrate that localized inflammation induced by turpentine oil (TURP) causes a time-dependent induction of interleukin (IL)-6 and has time-, gene- and tissue-specific effects on clock gene expression. More precisely, TURP blunts the peak of Per1 and Per2 expression in the liver while in other tissues, the expression nadir is elevated. In contrast, Rev-erbα expression remains relatively unaffected by TURP treatment. Co-treatment with the anti-inflammatory agent IL-1 receptor antagonist (IL-1Ra) did not alter the response of Per2 to TURP treatment in liver, despite the reduced induction of fever and IL-6 serum levels. This indicates that the TURP-mediated changes of Per2 in the liver might be due to factors other than systemic IL-6 and fever. Accordingly, IL-6 treatment had no effect on clock gene expression in HepG2 liver carcinoma cells. Altogether, we show that localized inflammation causes significant time-dependent changes in peripheral circadian clock gene expression, via a mechanism likely involving mediators independent from IL-6 and fever.
authors.affiliation: Douglas Mental Health University Institute, Montreal, QC, Canada.
authors.forename: Susan
authors.initials: S
authors.lastname: Westfall
authors.forename: Argel
authors.initials: A
authors.lastname: Aguilar-Valles
authors.forename: Valérie
authors.initials: V
authors.lastname: Mongrain
authors.forename: Giamal N
authors.initials: GN
authors.lastname: Luheshi
authors.forename: Nicolas
authors.initials: N
authors.lastname: Cermakian
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000502:physiology*; D056945:Hep G2 Cells; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology*; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D056950:Period Circadian Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014425:Turpentine / Q000633:toxicity
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; C513311:Per2 protein, rat; D056950:Period Circadian Proteins; D014425:Turpentine