腫瘤壞死因子
TNF(全稱腫瘤壞死因子,Tumor Necrosis Factor)是一種能夠直接殺傷腫瘤細(xì)胞而對正常細(xì)胞無明顯毒性的細(xì)胞因子,是迄今為止所發(fā)現(xiàn)的直接殺傷腫瘤作用最強(qiáng)的生物活性因子之一。最初是在1975年,由E.A. Carswell等人發(fā)現(xiàn),后于1985年經(jīng)Shalaby命名,由巨噬細(xì)胞產(chǎn)生的TNF命名為TNF-α,而由T淋巴細(xì)胞產(chǎn)生的淋巴毒素(lymphotoxin,LT)命名為TNF-β。
雖然TNF-α與TNF-β僅有約30%的同源性,但它們卻擁有共同的受體。TNFα的生物學(xué)活性占TNF總活性的70 %~95 %,因此目前常說的TNF多指TNF-α。
TNFα是一種涉及到系統(tǒng)性炎癥的細(xì)胞因子,主要由巨噬細(xì)胞分泌。TNFα的主要功能是調(diào)節(jié)免疫細(xì)胞,作為一種內(nèi)源性致熱原,可以導(dǎo)致發(fā)熱,引起細(xì)胞凋亡,組織腫瘤發(fā)生和病毒復(fù)制,并可以通過刺激細(xì)胞分泌IL1和IL6對敗血癥作出反應(yīng)。TNFα功能失調(diào)涉及多種疾病,比如阿爾茲海默癥、銀屑病、癌癥、重度抑郁和腸炎等。TNF家族除這兩種外還發(fā)現(xiàn)約30種。
華美生物TNF類蛋白產(chǎn)品涵蓋了絕大部分TNF家族成員,這里展示了部分蛋白產(chǎn)品圖片:
產(chǎn)品名稱 |
貨號(hào) |
規(guī)格 |
Recombinant Macaca mulatta Tumor necrosis factor protein (TNF), partial, (Active) |
CSB-AP003221MOW |
500ug/100ug/5ug |
Recombinant Mouse Tumor necrosis factor protein (Tnf), partial (Active) |
CSB-AP003471MO |
500ug/100ug/5ug |
Recombinant Human Lymphotoxin-alpha protein (LTA) |
CSB-AP002171HU |
500ug/100ug/10ug |
Recombinant Human Tumor necrosis factor ligand superfamily member 11 (TNFSF11), partial (Active) |
CSB-AP004851HU |
1mg(1mg*1 or 500ug*2)/500ug/50ug/10ug |
Recombinant Human Tumor necrosis factor (TNF), partial (Active) |
CSB-AP004861HU |
1mg(1mg*1 or 500ug*2)/500ug/50ug/10ug |
Recombinant Human Tumor necrosis factor (TNF), partial (Active) |
CSB-AP004871HU |
1mg(1mg*1 or 500ug*2)/500ug/50ug/10ug |
Recombinant Human Tumor necrosis factor (TNF), partial (Active) |
CSB-AP004881HU |
1mg(1mg*1 or 500ug*2)/500ug/50ug/10ug |
Recombinant Human Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B), partial (Active) |
CSB-AP004891HU |
1mg(1mg*1 or 500ug*2)/500ug/50ug/10ug |
Recombinant Human Tumor necrosis factor ligand superfamily member 10 (TNFSF10), partial (Active) |
CSB-AP004901HU |
1mg(1mg*1 or 500ug*2)/500ug/50ug/10ug |
Recombinant Human Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B), partial (Active) |
CSB-AP004921HU |
1mg(1mg*1 or 500ug*2)/500ug/50ug/10ug |
Recombinant Human Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B), partial (Active) |
CSB-AP004931HU |
1mg(1mg*1 or 500ug*2)/500ug/50ug/10ug |
Recombinant Human Lymphotoxin-alpha (LTA) (Active) |
CSB-AP004941HU |
1mg(1mg*1 or 500ug*2)/500ug/50ug/10ug |
Recombinant Human Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B) (Active) |
CSB-AP004951HU |
1mg(1mg*1 or 500ug*2)/500ug/50ug/10ug |
Recombinant Human Tumor necrosis factor receptor superfamily member 10C (TNFRSF10C), partial (Active) |
CSB-AP004961HU |
1mg(1mg*1 or 500ug*2)/500ug/50ug/10ug |
Recombinant Human Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A), partial (Active) |
CSB-AP004971HU |
1mg(1mg*1 or 500ug*2)/500ug/50ug/10ug |
Recombinant Human Tumor necrosis factor receptor superfamily member 10C (TNFRSF10C), partial (Active) |
CSB-AP004981HU |
1mg(1mg*1 or 500ug*2)/500ug/50ug/10ug |
Recombinant Human Tumor necrosis factor ligand superfamily member 15 (TNFSF15) (Active) |
CSB-AP004991HU |
1mg(1mg*1 or 500ug*2)/500μg/50μg/10μg |
Recombinant Mouse Tumor necrosis factor ligand superfamily member 11 (Tnfsf11), partial (Active) |
CSB-AP005021MO |
1mg(1mg*1 or 500ug*2)/500ug/50ug/10ug |
Recombinant Mouse Tumor necrosis factor (Tnf), partial (Active) |
CSB-AP005031MO |
1mg(1mg*1 or 500ug*2)/500ug/50ug/10ug |
Recombinant Mouse Tumor necrosis factor receptor superfamily member 10B (Tnfrsf10b), partial (Active) |
CSB-AP005041MO |
1mg(1mg*1 or 500ug*2)/500ug/50ug/10ug |
正如我們前面所說的,當(dāng)我們提到TNF時(shí),我們通常指的是TNFα。目前有關(guān)TNFα的作用機(jī)制已基本明了。 TNFα可以結(jié)合兩種受體,TNFR1(TNF受體1型)和TNFR2(TNF受體2型)。 TNFR1可在大多數(shù)組織中表達(dá),可以與膜上的TNF可溶性三聚體形式結(jié)合并活化。而TNFR2通常存在于免疫系統(tǒng)的細(xì)胞中,可以與膜結(jié)合的TNF同源三聚體形式起作用。但就目前的研究數(shù)據(jù)而言,大多數(shù)關(guān)于TNF信號(hào)傳導(dǎo)均來自TNFR1,而TNFR2的作用就相對較小。TNFα與受體結(jié)合后,可激活多條信號(hào)通路,包括NFκB和MAPK信號(hào)傳導(dǎo)途徑。
此外,基于TNFα可以殺死腫瘤細(xì)胞這一特性, TNFα抑制劑已被用于臨床。TNFα抑制劑是一種抑制對TNFα生理反應(yīng)的藥物。TNFα可參與自身免疫和免疫介導(dǎo)疾病,例如類風(fēng)濕性關(guān)節(jié)炎、強(qiáng)直性脊柱炎、炎性腸病、牛皮癬、化膿性汗腺炎和難治性哮喘,它本身就是引起炎癥的一個(gè)重要因素,所有TNF抑制劑可用于這些自身免疫和免疫介導(dǎo)疾病的治療。目前已上市的TNFα抑制劑包括依那西普、英夫利昔單抗、阿達(dá)木單抗、賽妥珠單抗和戈利木單抗,都是通過與TNFα結(jié)合來抑制其與對應(yīng)受體結(jié)合起作用。