Neural involvement plays a role in the genesis of the peripheral inflammatory process that contributes to the irradiation intestinal disorders. However, little is known about the role of vagus nerve in modulating inflammatory process in rat. Here, we have shown that the NF-κB activation was consistent with the acute overexpression of pro-inflammatory cytokines (IL- 1β, TNF-α, IL-6) at 3, 6, and 12 h induced by whole-body irradiation (8 Gy). Subdiaphragmatic vagotomy reduced NF-κB activation and cytokine transcription in the early period post-irradiation. In contrast, vagotomy amplified overexpression of irradiation-induced anti-cytokines (IL-10, IL-1Ra) and of receptors involved in anti-inflammatory effects (IL- 1RII, TNFRII). These results show that the vagus nerve is a pro-inflammatory pathway in early irradiation-induced intestinal inflammation.

Intracellular zinc levels are strictly regulated by zinc channels and zinc-binding proteins to maintain cellular zinc-dependent functions. We demonstrated a correlation between extracellular zinc concentration and intracellular exchangeable zinc levels using the fluorescent zinc-specific probes zinquin and zinpyr-1. The effect of extracellular zinc status on the regulation of the two trans-Golgi network directed zinc transporters ZnT-5 and ZnT-7 was next studied by real-time RT–PCR in zinc supplemented or depleted HeLa cells. While sub-toxic extracellular zinc addition strongly induced the efflux transporter ZnT-1 gene expression, consistent with its activation by the transcription factor MTF-1, treated HeLa cells did not display any change in ZnT-5 and ZnT-7 mRNA levels compared to control cells. In contrast, zinc depletion induced by non-toxic doses of the zinc chelator TPEN (N,N,N′,N′ tetrakis-(2 pyridylmethyl) ethylene diamine) resulted in a up to eight-fold induction of transporters ZnT-5 and ZnT-7 mRNA levels, providing the first evidence of a transcriptional control of these two zinc efflux transporters by zinc deficiency in cultured cells.

Purpose: 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 and Materials: 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.Conclusion: In vivo, irradiation induced a cascade of inflammatory responses that involved the transcription factor NF-kappaB; this inflammation was reduced by CAPE treatment. (C) 2004 Elsevier Inc.