DIURNAL, AGE, AND IMMUNE REGULATION OF INTERLEUKIN-1β AND INTERLEUKIN-1 TYPE 1 RECEPTOR IN THE MOUSE SUPRACHIASMATIC NUCLEUS

Sep 22, 2010Chronobiology international

Daily, age, and immune changes in a key inflammation signal and its receptor in the mouse body clock center

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Abstract

Expression of the proinflammatory cytokine interleukin-1β (IL-1β) and its receptor IL-1R1 was observed in the suprachiasmatic nucleus (SCN) of young mice, with temporal regulation noted for IL-1R1.

In young mice, both IL-1β and IL-1R1 are present in the SCN, but only IL-1R1 levels vary throughout the day.
Older mice exhibit lower IL-1β levels in the SCN compared to young mice, and IL-1R1 levels do not change over the 24-hour cycle.
Age-related differences in IL-1β and IL-1R1 expression were also found in the paraventricular nucleus of the hypothalamus.
Following an immune challenge with lipopolysaccharide (LPS), IL-1β levels in the SCN did not change, while IL-1R1 significantly increased at both 6 and 24 hours.
Cellular activation in the SCN was confirmed 24 hours post-LPS treatment, indicated by increased levels of c-Fos and p65-NF-κB.

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Circadian clocks serve to impose a near-24-h temporal architecture on an organism's physiology, metabolism, and behavior. In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus functions as the master circadian pacemaker. There is growing evidence that immunomodulators, such as cytokines, may impinge on circadian timekeeping. We examined whether there is endogenous expression of the proinflammatory cytokine interleukin-1β (IL-1β) and its signaling receptor IL-1R1 in the SCN of young and older mice across the diurnal cycle. We found expression of both IL-1β and IL-1R1 in the young SCN, although only IL-1R1 displayed temporal regulation. In the older SCN, levels of IL-1β were expressed at lower levels than in the young SCN, and IL-1R1 did not vary across the 24 h. We also report age-related day-night variation of IL-1β and IL-1R1 in the paraventricular nucleus (PVN) of the hypothalamus. Further, we examined the effect of peripheral immune challenge on IL-1β and IL-1R1 in the SCN. We found that IL-1β immunoreactivity was not altered 6 or 24 h after a septic dose of lipopolysaccharide (LPS; 5 mg/kg), whereas IL-1R1 was significantly up-regulated in the SCN both 6 and 24 h after LPS. We also demonstrate cellular activation in the SCN 24 h following LPS treatment, as evidenced by increased c-Fos and p65-NF-κB (nuclear factor kappa B) expression. Our results indicate that IL-1β and its associated signaling system may play a role in mediating the response of the circadian timing system to immune challenge as well as potentially contributing to the basal functioning of the SCN clock.

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DIURNAL, AGE, AND IMMUNE REGULATION OF INTERLEUKIN-1β AND INTERLEUKIN-1 TYPE 1 RECEPTOR IN THE MOUSE SUPRACHIASMATIC NUCLEUS

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