Endogenous alphaCGRP protects against concanavalin A-induced hepatitis in mice.
To evaluate hepatoprotective effect of alpha-calcitonin gene-related peptide (alphaCGRP), we compared the susceptibilities of alphaCGRP-/- and wild-type mice to concanavalin A (Con A)-induced hepatitis. Twelve hours after Con A administration, serum transaminases were markedly higher in alphaCGRP-/- than wild-type mice, and much more extensive TUNEL-positive lesions and DNA fragmentation were detected in the livers of alphaCGRP-/- mice. Notably, expression of IL-6 was selectively diminished in alphaCGRP-/- mice, suggesting that induction of IL-6 during acute inflammatory responses is blunted in alphaCGRP-/- mice. In addition, primary cultured alphaCGRP-/- hepatocytes were more susceptible to IFN-gamma-induced cell death than hepatocytes from wild-type mice. Administration of exogenous alphaCGRP reduced the incidence of apoptosis among hepatocytes and endothelial cells. It thus appears that alphaCGRP exerts a hepatoprotective effect by modulating cytokine expression and preventing apoptosis.
Kamiyoshi
Akiko
A
Department of Organ Regeneration, Shinshu University Graduate School of Medicine, Japan.
Sakurai
Takayuki
T
Ichikawa-Shindo
Yuka
Y
Fukuchi
Junichi
J
Kawate
Hisaka
H
Muto
Shin-ichi
S
Tagawa
Yoh-ichi
Y
Shindo
Takayuki
T
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000502:physiology* / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D003208:Concanavalin A; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D053938:DNA Fragmentation; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D007371:Interferon-gamma / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout
D016207:Cytokines; D003208:Concanavalin A; D007371:Interferon-gamma; D000410:Alanine Transaminase; D015740:Calcitonin Gene-Related Peptide