Adhesion of monocytes to type I collagen stimulates an APP-dependent proinflammatory signaling response and release of Abeta1-40.
Adhesion of monocytes to type I collagen stimulates an APP-dependent proinflammatory signaling response and release of Abeta1-40.
复制标题
DOI：
10.1186/1742-2094-7-22
复制
发表时间：
2010-03-19
影响因子：
9.3
通讯作者：
Combs CK
中科院分区：
文献类型：
--
作者：
Sondag CM;Combs CK
淀粉样前体蛋白(APP)是一种普遍表达的细胞表面蛋白，据报道参与介导细胞与细胞或细胞与基质的相互作用。先前的工作已经证明，APP与β1整合素在不同的细胞类型中共定位。为了确定APP在单核细胞系细胞上的功能，特别是利用人单核细胞系THP-1，我们评估了APP在与细胞外基质成分I型胶原黏附过程中的作用。下拉分析表明，THP-1与胶原的结合刺激了酪氨酸激酶相关的信号反应，包括随后的p38 MAP激酶的磷酸化和APP与α2β1整合素的结合增加。此外，细胞黏附依赖于APP的表达，因为与假手术对照组相比，APP siRNA敲除降低了THP-1与胶原的黏附。酪氨酸激酶依赖的信号反应的一个结果是IL-1β(IL-1β)和Aβ1-40的分泌增加，但不包括APP的Aβ1-42片段。IL-1β分泌的增加依赖于p38 MAP激酶活性，而Aβ1-40的分泌则需要Src家族激酶活性，因为特异性p38抑制剂SB202190和Src家族激酶抑制剂PP2分别抑制IL-1β和Aβ1-40的分泌。这些数据表明，APP参与了经典的整合素依赖的酪氨酸激酶相关的外周血单核细胞的黏附和激活。此外，作为黏附依赖性表型改变的一个组成部分，IL-1β和Aβ1-40的分泌增加需要不同的APP依赖信号。提示APP不仅在细胞-基质间的黏附中具有广泛的作用，而且在外周免疫细胞的功能中也可能具有广泛的作用。
Amyloid precursor protein (APP) is a ubiquitously expressed cell surface protein reported to be involved in mediating cell-cell or cell-matrix interactions. Prior work has demonstrated that APP co-localizes with β1 integrin in different cell types. In an effort to determine the function of APP on monocytic lineage cells, in particular, the human monocyte cell line, THP-1, was used to assess the role of APP during adhesion to the extracelluar matrix component type I collagen. Pull-down assays demonstrated that THP-1 adhesion to collagen stimulated a tyrosine kinase-associated signaling response which included subsequent phosphorylation of p38 MAP kinase and increased association of APP with α2β1 integrin, specifically. In addition, cell adhesion was dependent upon APP expression since APP siRNA knockdown attenuated THP-1 adhesion to collagen compared to mock transfected controls. One consequence of the tyrosine kinase-dependent signaling response was increased secretion of interleukin-1β (IL-1β) and Aβ1-40 but not the Aβ1-42 fragment of APP. Increased secretion of IL-1β was dependent upon p38 MAP kinase activity while Aβ1-40 secretion required Src family kinase activity since the specific p38 inhibitor, SB202190, and the Src family kinase inhibitor, PP2, attenuated IL-1β and Aβ1-40 secretion, respectively. These data demonstrate that APP is involved in classic integrin-dependent tyrosine kinase-associated adhesion and activation of peripheral monocytic cells. Moreover, divergent APP-dependent signaling is required for increased secretion of both IL-1β and Aβ1-40 as a component of the adhesion-dependent change in phenotype. This suggests that APP may have a broad role in not only mediating cell-matrix adhesion but also in the function of peripheral immune cells.
登录
查看更多内容
影响因子：
4.8
作者：
Cao, XW;Südhof, TC
通讯作者：
Südhof, TC
DOI：
10.1016/0167-4889(96)00015-8
发表时间：
1996-08-21
影响因子：
5.1
作者：
Bullido, MJ;MunozFernandez, MA;Valdivieso, F
通讯作者：
Valdivieso, F
影响因子：
4.4
作者：
Garnotel, R;Rittié, L;Gillery, P
通讯作者：
Gillery, P
影响因子：
2.2
作者：
Dackiw, APB;Nathens, AB;Rotstein, OD
通讯作者：
Rotstein, OD
影响因子：
4.7
作者：
Gonzalez-Velasquez, Francisco J.;Moss, Melissa A.
通讯作者：
Moss, Melissa A.