Cytokines induce NF-κB, Nurr1 and corticotropin-releasing factor gene transcription in hypothalamic 4B cells.
OBJECTIVE
In the hypothalamus, corticotropin-releasing factor (CRF) plays a central role in regulating stress responses. Cytokines are important mediators of the interaction between the neuroendocrine and immune systems, and are implicated in the regulation of CRF expression. Following inflammatory challenges, interleukin (IL)-1 or IL-6 stimulates the hypothalamic-pituitary-adrenal axis. CRF promoter contains multiple nuclear factor (NF)-kappaB and Nurr1 binding sites. In the present study, we determined the ability of the signaling pathways to activate the CRF gene in the hypothalamic paraventricular nucleus following inflammatory challenge.


METHODS
Cytokine-induced changes in CRF gene expression were examined in the hypothalamic system. Luciferase assay and Western blotting were performed to assess transcriptional activity and the nuclear translocation of transcriptional factors.


RESULTS
IL-1beta, IL-6 and tumor necrosis factor (TNF)-alpha stimulated the nuclear expression levels of NF-kappaB, NF-kappaB-dependent Nurr1 and c-Fos proteins. Direct stimulatory effects of TNF-alpha and IL-1beta, in addition to IL-6, were found on the transcriptional activity of the CRF gene in hypothalamic 4B cells.


CONCLUSIONS
These cytokines are involved in the regulation of CRF gene activity in hypothalamic cells.
Kageyama
Kazunori
K
Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. kkageyama @ hkg.odn.ne.jp
Kagaya
Saeko
S
Takayasu
Shinobu
S
Hanada
Komaki
K
Iwasaki
Yasumasa
Y
Suda
Toshihiro
T
D000818:Animals; D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D003346:Corticotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism; D016207:Cytokines / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D053583:Interleukin-1beta / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D051379:Mice; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000235:genetics* / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000276:immunology / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000276:immunology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics
D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D003346:Corticotropin-Releasing Hormone