ANALYSIS OF THE MECHANISM OF ULTRAVIOLET-(UV)-B RADIATION-INDUCED PROSTAGLANDIN-E2 SYNTHESIS BY HUMAN EPIDERMOID CARCINOMA-CELLS
ANALYSIS OF THE MECHANISM OF ULTRAVIOLET-(UV)-B RADIATION-INDUCED PROSTAGLANDIN-E2 SYNTHESIS BY HUMAN EPIDERMOID CARCINOMA-CELLS
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DOI：
10.1111/1523-1747.ep12365904
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发表时间：
1993-10-01
影响因子：
6.5
通讯作者：
KRUTMANN, J
中科院分区：
文献类型：
--
作者：
GREWE, M;TREFZER, U;KRUTMANN, J
已知用白细胞介素（IL）-1 α刺激培养的人角质形成细胞会引起前列腺素（PG）E2释放。紫外线（UV）B辐射诱导角质形成细胞PGE 2和细胞因子产生。本研究涉及UVB诱导的角质形成细胞衍生的细胞因子IL-1和肿瘤坏死因子（TNF）α及其相应的受体分子的UVB诱导的PGE 2释放的自分泌作用。在体外暴露的转化的人角质形成细胞（KB细胞）诱导PGE 2的生产五至八倍。如果在单克隆抗体（MoAb）M4的存在下培养辐照细胞，则这种增加被抑制了70%，该单克隆抗体M4通过与1型IL-1受体（IL-1 R）结合来阻断IL-1效应。相比之下，阻断2型IL-1 R的MoAb M22没有显著作用。将重组人TNF α添加到未照射的KB细胞中导致PGE 2合成增加5 - 8倍，并且这种增加可以通过用MoAb htr-9刺激KB细胞来模拟，MoAb htr-9通过结合55-kD TNF受体（TNFR）发挥TNF α样生物活性。UVB诱导的PGE 2合成在中和性抗TNF α-Ab的存在下被阻断50%，并且通过添加抗TNF α-Ab和MoAb M4两者被完全抑制。为了阐明PGE 2合成中可能的调节细胞内步骤，测定KB细胞中的特定环氧合酶活性。UVB治疗后，环氧合酶活性增加了两倍，但保持不变，如果照射KB细胞在抗TNF α-Ab加MoAb M4的存在下培养。这些研究表明，角质形成细胞衍生的TNF α和IL-1通过特定的细胞表面受体共同介导UVB诱导的PGE 2释放，并且一种细胞内机制是照射细胞的前列腺素合成能力增加。
Stimulation of cultured human keratinocytes with interleukin (IL)-1alpha is known to elicit prostaglandin (PG) E2 release. Ultraviolet (UV) B radiation induces keratinocyte PGE2 and cytokine production. The present study deals with the autocrine roles of UVB-induced, keratinocyte-derived cytokines IL-1 and tumor-necrosis-factor (TNF) alpha and their corresponding receptor molecules for UVB-induced PGE2 release. In vitro exposure of transformed human keratinocytes (KB cells) induced PGE2 production five- to eightfold. This increase was inhibited by 70%, if irradiated cells were cultured in presence of monoclonal antibody (MoAb) M4, which blocks IL-1 effects by binding to the type 1 IL-1 receptor (IL-1R). In contrast, MoAb M22, which blocks the type 2 IL-1R, had no significant effects. Addition of recombinant human TNFalpha to unirradiated KB cells resulted in five- to eightfold increased PGE2 synthesis, and this increase could be mimicked by stimulation of KB cells with MoAb htr-9, which exerts TNFalpha-like bioactivity by binding to the 55-kD TNF receptor (TNFR). UVB-induced PGE2 synthesis was blocked by 50% in the presence of neutralizing anti-TNFalpha-Ab, and was completely inhibited by addition of both anti-TNFalpha-Ab and MoAb M4. To elucidate a possible regulatory intracellular step in PGE2 synthesis, specific cyclooxygenase activity in KB cells was determined. Following UVB treatment, cyclooxygenase activity increased twofold, but remained unaltered, if irradiated KB cells were cultured in the presence of anti-TNFalpha-Ab plus MoAb M4. These studies indicate that keratinocyte-derived TNFalpha and IL-1 together mediate UVB-induced PGE2 release via specific cell surface receptors, and that one intracellular mechanism is an increased prostanoid-synthesizing capacity of irradiated cells.