C-fos and IL-2 gene expression in rat brain cells and splenic lymphocytes after nonantigenic and antigenic stimuli.
Immunostimulatory or immunosuppressive stress models were used: (1) rotation stress (RS) and (2) immobilization (restraint) stress (IS). Intravenous injection of tetanus toxoid (anatoxin) (TT) was chosen as the antigenic stimulus (500 micrograms/kg weight), and intravenous injection of saline solution was used as the control. Splenic lymphocytes (CBA mice) or different brain structures (Wistar and Sprague-Dawley rats) were analyzed. The c-fos and interleukin-2 (IL-2) mRNA expression was measured using a digoxigenin (Dig)-labeled cDNA probe by spot or in situ hybridization. Rotation stress stimulated IL-2 mRNA synthesis in lymphocytes in the presence of ConA and rIL-2 by 40%. IL-2 mRNA synthesis in lymphoid cells obtained from animals after IS and after IS in combination with the administration in vitro of the cytotoxic drug CsA to the splenic lymphocytes was inhibited (30% and 99%), accordingly, as compared with control rats. Induction of c-fos mRNA synthesis in rat brain cells was noted 30 minutes after RS in the hypothalamus (lateralis hypothalamic area, LHA), thalamus, corpus collosum, and sensorimotor zone of the brain cortex. IL-2 mRNA synthesis was shown two hours after RS in the same structures. The increased number of c-fos mRNA-positive cells two hours after TT injection was shown in the posterior hypothalamus area (PHA), LHA, dorsomedial nucleus (DMH), ventromedial nucleus (VMH), and anterior hypothalamus area (AHA) as compared to the effect of i.v. saline injection. Moreover, IL-2 mRNA-positive cell induction was noted in the PHA, DMH, and VMH. Six hours after TT injection, c-fos mRNA expression was decreased in the PHA, LHA, and AHA. Activation of c-fos and IL-2 mRNA was detected in the paraventricularis nucleus 6 hours after TT i.v. injection. Thus, inhibition or stimulation of IL-2 gene expression in lymphoid cells depends on the nature of the stressors. RS or antigenic stimuli induce c-fos and IL-2 gene expression in definite structures of the brain. The dynamics of this process are time dependent. The partial correlation between c-fos and IL-2 mRNA expression in localization in brain structures and time dependence was shown.
Department of General Pathology and Pathophysiology, Institute of Experimental Medicine, Russian Academy of Medical Sciences, 12 Acad. Pavlov Str., St. Petersburg 197376, Russia.
E A
EA
Korneva
S V
SV
Barabanova
O I
OI
Golovko
M A
MA
Nosov
N S
NS
Novikova
T B
TB
Kazakova
D000818:Animals; D000941:Antigens / Q000276:immunology; D001921:Brain / Q000276:immunology* / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000276:immunology; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D015213:Neuroimmunomodulation; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013154:Spleen / Q000276:immunology* / Q000503:physiopathology; D013312:Stress, Physiological / Q000276:immunology*
D000941:Antigens; D007376:Interleukin-2; D016760:Proto-Oncogene Proteins c-fos