The role of calcitonin gene-related peptide in cutaneous immunosuppression induced by repeated subinflammatory ultraviolet irradiation exposure

The role of calcitonin gene-related peptide in cutaneous immunosuppression induced by repeated subinflammatory ultraviolet irradiation exposure
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DOI:
10.1111/j.0906-6705.2004.00185.x
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发表时间:
2004-04-01
影响因子:
3.6
通讯作者:
Ansel, JC
Ansel, JC
中科院分区:
医学2区
文献类型:
--
作者:
Legat, FJ;Jaiani, LT;Ansel, JC

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紫外线(UV)光是一种有效的治疗皮肤病,如牛皮癣,其中皮肤神经感觉系统可能有致病作用。在这项研究中,我们研究了紫外线对皮肤神经感觉系统和降钙素基因相关肽(CGRP)的调节可能有助于反复亚炎症紫外线照射介导的局部免疫抑制。我们的研究结果表明,将无毛小鼠暴露于亚炎症紫外线下,每周3次,持续4周,显著增加了对CGRP免疫反应的表皮神经纤维(ENFs)的数量,但不改变ENFs的总数。酶联免疫吸附法测定的皮肤CGRP含量在暴露于该剂量的紫外线后也显著增加。这些影响在最后一次紫外线照射后1天最明显,在紫外线照射后1周减弱。观察CGRP在紫外光诱导的接触性超敏反应免疫抑制中的作用。我们的研究结果表明,全身给药的CGRP受体拮抗剂可以显著抑制紫外线对表皮2,4-二硝基-1-氟苯(DNFB)致敏的抑制作用。在紫外线照射前使用广谱防晒霜可以抑制皮肤CGRP的增加和阻断免疫抑制。这些发现支持CGRP在慢性反复亚炎症紫外线照射引起的局部免疫抑制中的作用。
Ultraviolet (UV) light is an effective treatment for skin disorders like psoriasis in which the cutaneous neurosensory system may have a pathogenic role. In this study, we examined the possibility that UV modulation of the cutaneous neurosensory system and calcitonin gene-related peptide (CGRP) may contribute to local immunosuppression mediated by repeated subinflammatory UV irradiation. Our results indicated that exposure of hairless mice to subinflammatory UV three times weekly for 4 weeks significantly increased the number of epidermal nerve fibers (ENFs) immunoreactive for CGRP without altering the total number of ENFs. The skin content of CGRP as measured by enzyme-linked immunosorbent assay was also significantly increased after exposure to this dose of UV. These effects were most apparent 1 day after the last UV exposure and declined 1 week after UV. The role of CGRP in UV-induced immunosuppression of contact hypersensitivity was then examined. Our results indicated that UV suppression of epicutaneous 2,4-dinitro-1-fluorobenzene (DNFB) sensitization could be significantly inhibited by a systemically administered CGRP receptor antagonist. A broad-spectrum sunscreen applied before UV exposure inhibited increased cutaneous CGRP and blocked immunosuppression. These findings support a role for CGRP in the local immunosuppression caused by chronic, repeated subinflammatory UV exposure.