Corticotropin-releasing hormone deficiency results in impaired splenocyte response to lipopolysaccharide.
Corticotropin-releasing hormone (Crh), a major mediator of the stress response, has been shown to exert both stimulatory and inhibitory effects on the regulation of the immune system, in vivo. In our present study, we used the Crh-/- mice to investigate the effect of Crh deficiency on leukocyte function in vitro. Our results show that following LPS treatment, TNF-alpha and IL-1beta expression was significantly compromised in Crh-/- splenocytes, an effect most likely mediated by the lower levels of NF-kappaB DNA binding activity measured in the same cells. Furthermore, we show here that the proliferation rate of Crh-/- splenocytes in response to LPS was decreased compared to Crh+/+ splenocytes. Taken together, our findings show that the presence of endogenous Crh is necessary for the normal function of leukocytes, in vitro.
Venihaki
Maria
M
Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Zhao
Jie
J
Karalis
Katia P
KP
D000818:Animals; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis / Q000172:deficiency* / Q000494:pharmacology / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D007375:Interleukin-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000235:genetics; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013154:Spleen / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003346:Corticotropin-Releasing Hormone