Acute induction of inflammatory cytokine expression after gamma-irradiation in the rat: effect of an NF-kappaB inhibitor.
OBJECTIVE
The pathologic changes within the intestinal muscle layer may be at the origin of the cytokines that account for acute radiation-induced inflammation. We were specifically interested in evaluating the efficacy of an inhibitor of nuclear transcription factor kappa B (NF-kappaB) activation that is involved in regulating cytokine expression.


METHODS
Cytokine expression was analyzed in the ileal muscularis layer by reverse transcriptase-polymerase chain reaction (RT-PCR) at 3 h, 6 h, and 3 days after a 10-Gy gamma whole-body irradiation of rats. Caffeic acid phenethyl ester (CAPE) was injected intraperitoneally (30 mg/kg) 15 min before irradiation and once a day for 3 days.


RESULTS
Interleukin (IL)-1beta, tumor necrosis factor alpha (TNF-alpha), and IL-6 mRNA increased at 3 h and 6 h after irradiation, and expression of IL-6 and IL-8 was elevated at 3 days. On the other hand, levels of the anti-inflammatory cytokine IL-10 were markedly lower on Day 3. Overexpression of IL-6 on Day 3 was combined with upregulation of the IL-6 receptors (gp130/gp80) and suppressor of cytokine signaling-3 (SOCS3) genes. CAPE treatment did not significantly change IL-1beta or TNF-alpha expressions in the irradiated rats; it increased IL-10 expression at 6 h but had no effect on it on Day 3. CAPE treatment inhibited the radiation-induced expression of IL-6, IL-6 receptors (IL-6rs), and SOCS3 at 3 days.


CONCLUSIONS
In vivo, irradiation induced a cascade of inflammatory responses that involved the transcription factor NF-kappaB; this inflammation was reduced by CAPE treatment.
Linard
Christine
C
Institute for Radioprotection and Nuclear Safety (IRSN), BP no 17, F-92262 Fontenay-aux-Roses Cedex, France. christine.linard@irsn.fr
Marquette
Christel
C
Mathieu
Jacques
J
Pennequin
André
A
Clarençon
Didier
D
Mathé
Denis
D
D000818:Animals; D002109:Caffeic Acids / Q000627:therapeutic use*; D004751:Enteritis / Q000209:etiology / Q000378:metabolism*; D005720:Gamma Rays; D007082:Ileum / Q000378:metabolism / Q000528:radiation effects; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism*; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism / Q000528:radiation effects*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011832:Radiation Injuries / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014916:Whole-Body Irradiation
D002109:Caffeic Acids; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; D016328:NF-kappa B; D019947:Receptors, Interleukin-6; D012097:Repressor Proteins; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol