IL-4 and IL-13 negatively regulate TNF-α- and IFN-γ-induced β-defensin expression through STAT-6, suppressor of cytokine signaling (SOCS)-1, and SOCS-3
IL-4 and IL-13 negatively regulate TNF-α- and IFN-γ-induced β-defensin expression through STAT-6, suppressor of cytokine signaling (SOCS)-1, and SOCS-3
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DOI：
10.4049/jimmunol.179.2.984
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发表时间：
2007-07-15
影响因子：
4.4
通讯作者：
Howell, Michael D.
中科院分区：
文献类型：
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作者：
Albanesi, Cristina;Fairchild, Heather R.;Howell, Michael D.
人p -防御素（HBDs）是一类主要的抗菌肽，在先天免疫应答中发挥重要作用，然而，这些抗菌肽的诱导和调控尚不清楚。我们在这里证明了用tnf - α / ifn - γ刺激角质形成细胞通过激活STAT-1和NF-KB信号诱导HBD-2和HBD-3。我们进一步证明IL-4和IL-13激活STAT-6并诱导细胞因子信号(SOCS)-1和-3的抑制因子。这会干扰STAT-1和NF-KB信号，从而抑制tnf - α / ifn - γ介导的HBD-2和HBD-3的诱导。这些数据表明，靶向stat -1信号通路或细胞因子信号表达抑制因子可增强p -防御素的表达，为减少p -防御素缺乏症相关疾病的感染提供了一种新的治疗策略。
Human P-defensins (HBDs) are a major class of antimicrobial peptides that play an important role in the innate immune response, however, the induction and regulation of these antimicrobial peptides is not well understood. We demonstrate here that stimulation of keratinocytes with TNF-alpha/IFN-gamma induces HBD-2 and HBD-3 by activating STAT-1 and NF-KB signaling. We further demonstrate that IL-4 and IL-13 activate STAT-6 and induce the suppressors of cytokine signaling (SOCS)-1 and -3. This interferes with STAT-1 and NF-KB signaling, thereby inhibiting TNF-alpha/IFN-gamma-mediated induction of HBD-2 and HBD-3. These data suggest that targeting the STAT-1-signaling pathway or suppressor of cytokine signaling expression enhances P-defensin expression and represents a new therapeutic strategy for reduction of infection in human diseases associated with P-defensin deficiency.