Toll-like receptor signalling induces the expression of serum amyloid A in epidermal keratinocytes and dermal fibroblasts
Toll-like receptor signalling induces the expression of serum amyloid A in epidermal keratinocytes and dermal fibroblasts
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DOI：
10.1111/ced.13604
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发表时间：
2019-01-01
影响因子：
4.1
通讯作者：
Iwatsuki, K.
中科院分区：
文献类型：
--
作者：
Morizane, S.;Kajita, A.;Iwatsuki, K.
Toll样受体（TLR）通过感知病原体或损伤相关的分子模式在先天性免疫应答中发挥关键作用。表皮角质形成细胞和真皮成纤维细胞在TLR配体刺激下也产生促炎细胞因子和趋化因子。血清淀粉样蛋白A（SAA）是继发性淀粉样变性发病的重要因素，并具有免疫调节功能。SAA主要由肝细胞产生，但也由多种细胞产生，包括免疫细胞、内皮细胞、滑膜细胞和表皮角质形成细胞。目的研究TLR配体对正常人表皮角质形成细胞（NHEK）和正常人真皮成纤维细胞（NHDFs）SAA表达的影响，探讨TLR配体对SAA表达的影响。结果TLR 1/2、3、5和2/6配体通过核因子-κ B诱导NHEKs表达SAA。在NHDF中，TLR 1/2和TLR 2/6配体增加SAA表达。SAA通过TLR 1/2和NF-κ B在NHDFs中进一步诱导其自身的表达，如先前报道的NHEKs.Conclusions我们的研究结果提供了新的证据表明，皮肤的先天免疫反应有助于SAA的产生，这可能会导致全身并发症的风险增加，如隐性营养不良性大疱性表皮淀粉样变性。
Background Toll-like receptors (TLRs) play critical roles in innate immune response by sensing pathogen- or damage-associated molecular patterns. Epidermal keratinocytes and dermal fibroblasts also produce proinflammatory cytokines and chemokines under stimulation with TLR ligands. Serum amyloid A (SAA) is an essential factor in the pathogenesis of secondary amyloidosis, and also has immunomodulatory functions. SAA are produced mainly by hepatocytes but also by a variety of cells, including immune cells, endothelial cells, synoviocytes, and epidermal keratinocytes. However, SAA expression in human dermal fibroblasts has not been shown to date.Aim To investigate the effect of TLR ligands on SAA expression in epidermal keratinocytes and dermal fibroblasts.Methods We investigated whether TLR ligands induce the expression of SAA in normal human epidermal keratinocytes (NHEKs) and normal human dermal fibroblasts (NHDFs) by real-time quantitative PCR and ELISA. The effect of SAA on its own expression in NHDFs was also studied.Results SAA expression was induced via nuclear factor-kappa B by TLR1/2, 3, 5 and 2/6 ligands in NHEKs. In NHDFs, TLR1/2 and TLR2/6 ligands increased SAA expression. SAA further induced its own expression via TLR1/2 and NF-kappa B in NHDFs, as previously reported for NHEKs.Conclusions Our results provide new evidence that the skin's innate immune response contributes to the production of SAA, which might lead to an increased risk of systemic complications such as secondary amyloidosis of recessive dystrophic epidermolysis bullosa.