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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(duì)正常細(xì)胞無(wú)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(shuō)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(guò)刺激細(xì)胞分泌IL1和IL6對(duì)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 Human Tumor necrosis factor receptor superfamily member 12A protein (TNFRSF12A), partial (Active) CSB-AP001931HU 500ug/100ug/5ug
Recombinant Human Tumor necrosis factor receptor superfamily member 9 protein (TNFRSF9), partial CSB-AP001951HU 500ug/100ug/5ug
Recombinant Human Tumor necrosis factor ligand superfamily member 9 (TNFSF9), partial (Active) CSB-AP001961HU 500ug/100ug/5ug
Recombinant Human Tumor necrosis factor protein (TNF), partial (Active) CSB-AP002141HU 500ug/100ug/10ug
Recombinant Human Tumor necrosis factor protein (TNF), partial (Active) CSB-AP002151HU 500ug/100ug/10ug
Recombinant Human Tumor necrosis factor protein (TNF), partial (Active) CSB-AP002161HU 500ug/100ug/10ug
Recombinant Human Tumor necrosis factor receptor superfamily member 13C protein (TNFRSF13C), partial (Active) CSB-AP002181HU 500ug/100ug/10ug
Recombinant Human Tumor necrosis factor ligand superfamily member 13B (TNFSF13B), partial (Active) CSB-AP002191HU 500ug/100ug/5ug
Recombinant Human CD40 ligand (CD40LG), partial (Active) CSB-AP002211HU 500ug/100ug/10ug
Recombinant Human Tumor necrosis factor receptor superfamily member 17 protein (TNFRSF17), partial (Active) CSB-AP002271HU 500ug/100ug/5ug
Recombinant Human Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B),Partial (Active) CSB-AP002291HU 500ug/100ug/10ug
Recombinant Human Tumor necrosis factor receptor superfamily member 13B protein (TNFRSF13B), partial (Active) CSB-AP002301HU 500ug/100ug/5ug
Recombinant Human Tumor necrosis factor receptor superfamily member 6 protein (FAS), partial (Active) CSB-AP002311HU 500ug/100ug/5ug
Recombinant Human Tumor necrosis factor receptor superfamily member 11A protein (TNFRSF11A), partial (Active) CSB-AP002321HU 500ug/100ug
Recombinant Human Tumor necrosis factor ligand superfamily member 15 protein (TNFSF15), partial (Active) CSB-AP002341HU 500ug/100ug/5ug
Recombinant Human Tumor necrosis factor ligand superfamily member 18 protein (TNFSF18), partial (Active) CSB-AP002351HU 500ug/100ug/5ug
Recombinant Human Tumor necrosis factor receptor superfamily member 1A protein (TNFRSF1A), partial (Active) CSB-AP002361HU 500ug/100ug/5ug
Recombinant Human Tumor necrosis factor receptor superfamily member 1B protein (TNFRSF1B), partial (Active) CSB-AP002371HU 500ug/100ug/5ug
Recombinant Human Tumor necrosis factor receptor superfamily member 11B protein (TNFRSF11B), partial (Active) CSB-AP002991HU 500ug/100ug/10ug
Recombinant Human Tumor necrosis factor receptor superfamily member 11B protein (TNFRSF11B), partial (Active) CSB-AP003001HU 500ug/100ug/10ug

正如我們前面所說(shuō)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(lái)自TNFR1,而TNFR2的作用就相對(duì)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(duì)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(guò)與TNFα結(jié)合來(lái)抑制其與對(duì)應(yīng)受體結(jié)合起作用。