Lipopolysaccharide-induced elevation and secretion of interleukin-1β in the submandibular gland of male mice

Lipopolysaccharide-induced elevation and secretion of interleukin-1β in the submandibular gland of male mice
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DOI:
10.1111/j.1365-2567.2005.02212.x
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发表时间:
2005-10-01
期刊:
影响因子:
6.4
通讯作者:
Hosoi, K
Hosoi, K
中科院分区:
医学2区
文献类型:
--
作者:
Yao, CJ;Li, XF;Hosoi, K

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腹腔注射脂多糖(LPS)(400μg/kg体重)可诱导C3H/HeN小鼠下颌下腺(SMG)炎症细胞因子如白细胞介素(IL)-1β、IL-6和肿瘤坏死因子(TNF)-αmRNA的表达,但对Toll样受体4(TLR-4(-)突变株C3H/HeJ小鼠)无影响。突变体)。野生型小鼠 SMG 中这些细胞因子的 mRNA 水平早在注射后 3 小时就增加,在 3-6 小时达到峰值,并在 24 小时再次下降。在本研究中,我们特别关注IL-1β,并详细研究了该内毒素的诱导作用。上颈干和鼓索神经的去神经并没有减少 LPS 诱导的 SMG 中 IL-1 β mRNA 的升高,表明中枢神经系统在此诱导中无关。 TLR-4 mRNA 和蛋白质在 SMG 中强烈表达,表明 LPS 对该腺体有直接作用。 IL-1 β蛋白定位于颗粒曲管(GCT)细胞的分泌颗粒中,其在腺体中的分子量分别为17.5和20 kDa。在 C3H/HeN 小鼠中注射 LPS 6 小时后,相同大小的 IL-1 β 出现在唾液中,但在 C3H/HeJ 小鼠中则没有。因此,本研究表明,IL-1β(一种炎症细胞因子)响应腹膜内注射的内毒素而被诱导并分泌到唾液中。
The intraperitoneal injection of lipopolysaccharide (LPS) (400 mu g/kg body weight) induced the expression of mRNAs of inflammatory cytokines such as interleukin (IL)-1 beta, IL-6 and tumour necrosis factor (TNF)-alpha in the submandibular gland (SMG) of C3H/HeN mice but not that of C3H/HeJ mice, a mutant strain for Toll-like receptor-4 (TLR-4(-) mutant). The mRNA levels of these cytokines in the SMG of the wild-type mice increased as early as 3 hr after injection, peaked at 3-6 hr, and had decreased again by 24 hr. In this study, we particularly focused on IL-1 beta, and induction by this endotoxin was investigated in detail. Denervation of the superior cervical trunk and chorda tympani nerve did not diminish the LPS-induced elevation of IL-1 beta mRNA in the SMG, indicating the irrelevance of the central nervous system in this induction. TLR-4 mRNA and protein were shown to be strongly expressed in the SMG, suggesting the direct action of LPS on this gland. IL-1 beta proteins were localized in the secretory granules of granular convoluted tubular (GCT) cells, and their molecular weights in the gland were 17.5 and 20 kDa. IL-1 beta of the same size appeared in the saliva 6 hr after LPS injection in C3H/HeN but not in C3H/HeJ mice. The present study thus suggests that IL-1 beta, an inflammation cytokine, is induced and secreted into the saliva in response to endotoxin injected intraperitoneally.