Andrews Ellen, Feldhoff Pamela, Feldhoff Richard, Lassiter Herbert
Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville School of Medicine, 571 South Floyd Street, Suite 300, Louisville, KY 40202, USA.
Cytokine. 2003 Sep 21;23(6):164-9. doi: 10.1016/s1043-4666(03)00219-9.
The mechanisms that control complement protein synthesis are incompletely understood. Recent evidence suggests that cytokines are involved in the regulation of hepatic synthesis of circulating complement components. Therefore, we compared the effects of human recombinant IL-1alpha, IL-1beta, IL-6, IFN-gamma, and TNF-alpha individually or in combination, on HepG2 secretion of complement component C3, the major opsonic protein of the complement system. HepG2 cells were incubated with each cytokine alone and with various combinations of the cytokines. At 24, 48, 72, and 96 h of incubation, the C3 and albumin secreted by the HepG2 cells were quantified by a sandwich ELISA. IL-1alpha and IFN-gamma significantly enhanced C3 secretion by the cells (P<0.02 vs. control cells). IL-1beta when combined with either IL-6 or IFN-gamma also increased C3 secretion (P<0.03 vs. control cells). The stimulatory effect on HepG2 cells by the IL-1beta/IL-6 combination was synergistic. With the exception of IL-1alpha, which increased albumin secretion, HepG2 secretion of albumin was not affected by incubation with individual cytokines or the cytokine combinations. Therefore, IL-1alpha, IFN-gamma, and the combination of IL-1beta with IL-6 or IFN-gamma specifically enhanced C3 secretion by HepG2 cells. The greatest magnitude of C3 secretion was induced by the combination of IL-1beta and IL-6.
控制补体蛋白合成的机制尚未完全明确。最近有证据表明,细胞因子参与循环补体成分肝脏合成的调节。因此,我们比较了重组人白细胞介素-1α、白细胞介素-1β、白细胞介素-6、干扰素-γ和肿瘤坏死因子-α单独或联合使用时,对补体系统主要调理蛋白补体成分C3在HepG2细胞中分泌的影响。将HepG2细胞分别与每种细胞因子以及细胞因子的各种组合进行孵育。在孵育24、48、72和96小时时,通过夹心ELISA对HepG2细胞分泌的C3和白蛋白进行定量。白细胞介素-1α和干扰素-γ显著增强了细胞的C3分泌(与对照细胞相比,P<0.02)。白细胞介素-1β与白细胞介素-6或干扰素-γ联合使用时也增加了C3分泌(与对照细胞相比,P<0.03)。白细胞介素-1β/白细胞介素-6组合对HepG2细胞的刺激作用具有协同性。除了增加白蛋白分泌的白细胞介素-1α外,与单个细胞因子或细胞因子组合孵育未影响HepG2细胞白蛋白的分泌。因此,白细胞介素-1α、干扰素-γ以及白细胞介素-1β与白细胞介素-6或干扰素-γ的组合特异性增强了HepG2细胞的C3分泌。白细胞介素-1β和白细胞介素-6的组合诱导的C3分泌量最大。