CGRP, PACAP, and VIP modulate langerhans cell function by inhibiting NF-κB activation
CGRP, PACAP, and VIP modulate langerhans cell function by inhibiting NF-κB activation
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DOI：
10.1038/sj.jid.5700858
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发表时间：
2007-10-01
影响因子：
6.5
通讯作者：
Granstein, Richard D.
中科院分区：
文献类型：
--
作者：
Ding, Wanhong;Wagner, John A.;Granstein, Richard D.
降钙素基因相关肽（CGRP）、垂体腺苷酸环化酶激活多肽（PACAP）和血管活性肠肽（VIP）等神经肽抑制朗格汉斯细胞（LC）抗原呈递并调节细胞因子的产生。我们已经测试了这些神经肽（NP）通过调节nf - κ B的激活来抑制LC功能的假设。脂多糖（LPS）在LC样细胞系（XS52）和表皮LC中激活nf - κ B，富集程度接近95%，这种作用被每种NP抑制。此外，CGRP、PACAP和VIP抑制I kappa B激酶β (P-IKK β)的磷酸化，阻止I kappa B α的降解，抑制NF-kappa B的活化。因此，这些NP通过降低NF-kappa B的活化来调节LC功能。bay11 - 7085是一种IKK抑制剂，可减少LPS刺激的XS52细胞的肿瘤坏死因子α (TNF α)的产生，并抑制LC向体外T细胞克隆呈递抗原的能力。每个NP也抑制LPS诱导的XS52细胞分泌TNF α， LC富集到相似的95%均匀性。我们认为，CGRP、PACAP和VIP对LC功能的抑制活性至少部分是通过抑制P- IKK β介导的，这可以阻止I κ B α的降解和nf - κ B的激活。
The neuropeptides calcitonin gene- related peptide ( CGRP), pituitary adenylate cyclase- activating polypeptide ( PACAP), and vasoactive intestinal peptide ( VIP) suppress Langerhans cell ( LC) antigen presentation and modulate cytokine production. We have tested the hypothesis that these neuropeptides ( NP) inhibit LC function by modulating activation of NF-kappa B. Lipopolysaccharide ( LPS) activates NF-kappa B in both a LC- like cell line (XS52) and epidermal LC enriched to similar to 95% and this effect is inhibited by each of the NP. Furthermore, CGRP, PACAP, and VIP suppress phosphorylation of I kappa B kinase beta(P-IKK beta), prevent degradation of the I kappa B alpha, and inhibit activation of NF-kappa B. Thus, these NP modulate LC function by reducing NF-kappa B activation. Bay 11- 7085, an inhibitor of IKK, reduced tumor necrosis factor-alpha ( TNF alpha) production from LPS- stimulated XS52 cells and inhibited the ability of LC to present antigen to a T- cell clone in vitro. Each NP also inhibited LPS- induced secretion of TNF alpha by XS52 cells and LC enriched to similar to 95% homogeneity. We suggest that the inhibitory activities of CGRP, PACAP, and VIP on LC function are mediated, at least in part, by inhibition of P- IKK beta, which prevents I kappa B alpha degradation and activation of NF-kappa B. Modulation of this signaling pathway may be useful for therapeutic modulation of immunity in the skin.