A critical pole for p38 mitogen-activated protein kinase in the maturation of human blood-derived dendritic cells induced by lipopolysaccharide, TNF-α, and contact sensitizers
A critical pole for p38 mitogen-activated protein kinase in the maturation of human blood-derived dendritic cells induced by lipopolysaccharide, TNF-α, and contact sensitizers
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DOI：
10.4049/jimmunol.166.6.3837
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发表时间：
2001-03-15
影响因子：
4.4
通讯作者：
Hauser, C
中科院分区：
文献类型：
--
作者：
Arrighi, JF;Rebsamen, M;Hauser, C
我们研究了丝裂原活化蛋白激酶（MAPK）在人血单核细胞来源的CD 83-树突状细胞（DC）成熟中的作用。成熟剂如LPS和TNF-α诱导MAPK三个家族成员的磷酸化，（细胞外信号调节激酶1/2、p46/54 c-Jun N-末端激酶和p38 MAPK），SB 203580，p38 MAPK的抑制剂，而非细胞外信号调节激酶1/2通路阻断剂PD 98059，抑制LPS和TNF-α诱导的CD 1a、CD 40、CD 80、CD 86、HLA-DR和DC成熟标志物CD 83的上调。此外，SB 203580抑制同种异体刺激能力的增强，并部分阻止LPS和TNF-α诱导的FITC-葡聚糖摄取的下调。同样，SB 203580部分阻止LPS和TNF-α刺激后IL-1 α、IL-1 β、IL-1 Ra和TNF-α mRNA的上调，除了由LPS诱导的生物活性TNF-α的释放，由接触致敏剂2，4-二硝基氟苯和NiSO 4诱导的DC成熟，如通过CD 80、CD 86和CD 83的上调所见，也与p38 MAPK的磷酸化偶联，并且被SB 203580抑制。不诱导DC成熟的刺激物SDS和苯扎氯铵不触发p38 MAPK磷酸化。总之，这些数据表明p38 MAPK的磷酸化对于未成熟DC的成熟是关键的，这些结果也表明，p38 MAPK磷酸化在DC可能成为有用的识别潜在的皮肤接触致敏剂。
We investigated the involvement of mitogen-activated protein kinases (MAPKs) in the maturation of CD83- dendritic cells (DC) derived from human blood monocytes, Maturating agents such as LPS and TNF-alpha induced the phosphorylation of members of the three families of MAPK (extracellular signal-regulated kinase 1/2, p46/54 c-Jun N-terminal kinase, and p38 MAPK), SB203580, an inhibitor of the p38 MAPK, but not the extracellular signal-regulated kinase 1/2 pathway blocker PD98059, inhibited the up-regulation of CD1a, CD40, CD80, CD86, HLA-DR, and the DC maturation marker CD83 induced by LPS and TNF-alpha, In addition, SB203580 inhibited the enhancement of the allostimulatory capacity and partially prevented the down-regulation of FITC-dextran uptake induced by LPS and TNF-cu, Likewise, SB203580 partially prevented the up-regulation of IL-1 alpha, IL-1 beta, IL-1Ra, and TNF-alpha mRNA upon stimulation with LPS and TNF-alpha, as well as the release of bioactive TNF-alpha induced by LPS, DC maturation induced by the contact sensitizers 2,4-dinitrofluorobenzene and NiSO4, as seen by the up-regulation of CD80, CD86, and CD83, was also coupled to the phosphorylation of p38 MAPK, and was inhibited by SB203580, The irritants SDS and benzalkonium chloride that do not induce DC maturation did not trigger p38 MAPK phosphorylation, Together, these data indicate that phosphorylation of p38 MAPK is critical for the maturation of immature DC, These results also suggest that p38 MAPK phosphorylation in DC may become useful for the identification of potential skin contact sensitizers.