J R Heyen

University of Illinois, Urbana-Champaign, Urbana, IL, United States

Are you J R Heyen?

Claim your profile

Publications (6)12.07 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Proinflammatory cytokines inhibit learning and memory but the significance of interleukin-6 (IL-6) in acute cognitive deficits induced by the peripheral innate immune system is not known. To examine the functional role of IL-6 in hippocampus-mediated cognitive impairments associated with peripheral infections, C57BL6/J (IL-6(+/+)) and IL-6 knock-out (IL-6(-/-)) mice were trained in a matching-to-place version of the water maze. After an acquisition phase, IL-6(+/+) mice injected intraperitoneally with lipopolysaccharide (LPS) exhibited deficits in working memory. However, IL-6(-/-) mice were refractory to the LPS-induced impairment in working memory. To determine the mechanism by which IL-6 deficiency conferred protection from disruption in working memory, plasma IL-1beta and tumor necrosis factor alpha (TNFalpha), c-Fos immunoreactivity in the nucleus of the solitary tract (NTS), and steady-state levels of IL-1beta and TNFalpha mRNA in neuronal layers of the hippocampus were determined in IL-6(+/+) and IL-6(-/-) mice after injection of LPS. Plasma IL-1beta and TNFalpha and c-Fos immunoreactivity in the NTS were increased similarly in IL-6(+/+) and IL-6(-/-) mice after LPS, indicating high circulating levels of IL-1beta and TNFalpha and activation of vagal afferent pathways were not sufficient to disrupt working memory in the absence of IL-6. However, the LPS-induced upregulation of IL-1beta and TNFalpha mRNA that was evident in hippocampal tissue of IL-6(+/+) mice was greatly attenuated or entirely absent in IL-6(-/-) mice. Collectively, these data suggest that humoral and neural immune-to-brain communication pathways are intact in IL-6-deficient mice but that, in the absence of IL-6, the central cytokine compartment is hyporesponsive.
    Journal of Neuroscience 11/2006; 26(42):10709-16. · 6.91 Impact Factor
  • Brain Behavior and Immunity - BRAIN BEHAV IMMUN. 01/2005; 19(4).
  • J R Heyen, S Ye, B N Finck, R W Johnson
    [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this study was to determine if interleukin (IL)-10 inhibits lipopolysaccharide (LPS)-induced IL-6 production in microglia by inhibiting activation of nuclear factor-kappaB (NF-kappaB). N13 microglia (a murine microglial cell line) and primary microglia from neonatal mice were cultured in the presence or absence of LPS and increasing amounts of murine IL-10 for 24 h. As predicted, LPS treatment increased supernatant IL-6 concentration in both N13 and primary microglia cultures. Pretreatment with IL-10, however, decreased LPS-induced IL-6 secretion in a dose-dependent manner in both culture systems. Likewise, ribonuclease protection assays showed that LPS increased steady-state IL-6 mRNA levels, but that pretreatment with IL-10 blocked the LPS-induced increase in IL-6 mRNA. Because NF-kappaB is the predominant transcription factor responsible for IL-6 transcription in response to inflammatory stimuli, it was hypothesized that IL-10 inhibited IL-6 production by preventing nuclear translocation of NF-kappaB. Consistent with this idea, LPS increased nuclear translocation of NF-kappaB as assessed by gel mobility shift assay. Supershift assays and immunocytochemical staining showed that both the p50 and p65 subunits of NF-kappaB translocated from the cytoplasm to the nucleus upon LPS stimulation. Pretreatment with IL-10, however, inhibited LPS-induced activation of NF-kappaB. Furthermore, inhibition of NF-kappaB activity with tosyl-Phe-chloromethlyketone (a serine protease inhibitor that prevents degradation of the NF-kappaB-IkappaB complex), completely blocked LPS-induced IL-6 production. These data suggest that IL-10 inhibited IL-6 production in microglia by decreasing the activity of NF-kappaB and, therefore, extend what little is known of the intricate relationship between anti-inflammatory and inflammatory cytokines in the central nervous system.
    Molecular Brain Research 05/2000; 77(1):138-47. · 2.00 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this study was to determine if interleukin (IL)-10 inhibits lipopolysaccharide (LPS)-induced IL-6 production in microglia by inhibiting activation of nuclear factor-κB (NF-κB). N13 microglia (a murine microglial cell line) and primary microglia from neonatal mice were cultured in the presence or absence of LPS and increasing amounts of murine IL-10 for 24 h. As predicted, LPS treatment increased supernatant IL-6 concentration in both N13 and primary microglia cultures. Pretreatment with IL-10, however, decreased LPS-induced IL-6 secretion in a dose-dependent manner in both culture systems. Likewise, ribonuclease protection assays showed that LPS increased steady-state IL-6 mRNA levels, but that pretreatment with IL-10 blocked the LPS-induced increase in IL-6 mRNA. Because NF-κB is the predominant transcription factor responsible for IL-6 transcription in response to inflammatory stimuli, it was hypothesized that IL-10 inhibited IL-6 production by preventing nuclear translocation of NF-κB. Consistent with this idea, LPS increased nuclear translocation of NF-κB as assessed by gel mobility shift assay. Supershift assays and immunocytochemical staining showed that both the p50 and p65 subunits of NF-κB translocated from the cytoplasm to the nucleus upon LPS stimulation. Pretreatment with IL-10, however, inhibited LPS-induced activation of NF-κB. Furthermore, inhibition of NF-κB activity with tosyl-Phe-chloromethlyketone (a serine protease inhibitor that prevents degradation of the NF-κB–IκB complex), completely blocked LPS-induced IL-6 production. These data suggest that IL-10 inhibited IL-6 production in microglia by decreasing the activity of NF-κB and, therefore, extend what little is known of the intricate relationship between anti-inflammatory and inflammatory cytokines in the central nervous system.
    Molecular Brain Research. 01/2000;
  • [Show abstract] [Hide abstract]
    ABSTRACT: The level of locomotor activity, body temperature (T(B)), and feeding for adult (3-5-month old) and aged (22-24-month old) male BALB/c mice was determined and the sensitivity of the two age groups to the anorectic, febrile, and behavioral properties of interleukin-1beta (IL-1beta) in the brain was examined. Baseline locomotor activity and T(B) were markedly lower in aged mice than in adults and the circadian rhythm for both activity and T(B) were disrupted in the aged. Adult and aged mice consumed similar amounts of food during the daytime and nighttime, but aged mice made longer, less frequent visits to the feed cup. To determine if aging affects the responsiveness to central IL-1beta, adult and aged mice were injected intracerebroventricularly with PBS or IL-1beta. Compared to age-matched PBS controls, IL-1beta increased T(B) in both adult and aged mice. The peak deltaT(B) was greater in aged mice than in adults, but because of a lower baseline T(B) in aged mice, peak T(B) after IL-1beta was not different between groups. Locomotor activity of aged mice receiving PBS was about half that of PBS-injected adults and was not depressed further by IL-1beta. However, compared to age-matched PBS controls, centrally administered IL-1beta depressed food intake more in aged mice than in adults. These data indicate that even though feeding, locomotor activity, and T(B) are affected by aging, the central component of the inflammatory response mediated by IL-1beta is retained.
    Physiology & Behavior 07/1999; 66(4):673-9. · 3.16 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The level of locomotor activity, body temperature (TB), and feeding for adult (3–5-month old) and aged (22–24-month old) male BALB/c mice was determined and the sensitivity of the two age groups to the anorectic, febrile, and behavioral properties of interleukin-1β (IL-1β) in the brain was examined. Baseline locomotor activity and TB were markedly lower in aged mice than in adults and the circadian rhythm for both activity and TB were disrupted in the aged. Adult and aged mice consumed similar amounts of food during the daytime and nighttime, but aged mice made longer, less frequent visits to the feed cup. To determine if aging affects the responsiveness to central IL-1β, adult and aged mice were injected intracerebroventricularly with PBS or IL-1β. Compared to age-matched PBS controls, IL-1β increased TB in both adult and aged mice. The peak ΔTB was greater in aged mice than in adults, but because of a lower baseline TB in aged mice, peak TB after IL-1β was not different between groups. Locomotor activity of aged mice receiving PBS was about half that of PBS-injected adults and was not depressed further by IL-1β. However, compared to age-matched PBS controls, centrally administered IL-1β depressed food intake more in aged mice than in adults. These data indicate that even though feeding, locomotor activity, and TB are affected by aging, the central component of the inflammatory response mediated by IL-1β is retained.
    Physiology & Behavior - PHYSIOL BEHAV. 01/1999; 66(4):673-679.