MRC Human Genetics Unit, Western General Hospital, Institute of Genetics and Molecular Medicine, Edinburgh, Scotland, UK.
Eur J Immunol. 2010 Apr;40(4):1073-8. doi: 10.1002/eji.200940041.
Beta-defensins are antimicrobial peptides with an essential role in the innate immune response. In addition beta-defensins can also chemoattract cells involved in adaptive immunity. Until now, based on evidence from dendritic cell stimulation, human beta defensin-3 (hBD3) was considered pro-inflammatory. We present evidence here that hBD3 lacks pro-inflammatory activity in human and mouse primary Mphi. In addition, in the presence of LPS, hBD3 and the murine orthologue Defb14 (but not hBD2), effectively inhibit TNF-alpha and IL-6 accumulation implying an anti-inflammatory function. hBD3 also inhibits CD40/IFN-gamma stimulation of Mphi and in vivo, hBD3 significantly reduces the LPS-induced TNF-alpha level in serum. Recent work has revealed that hBD3 binds melanocortin receptors but we provide evidence that these are not involved in hBD3 immunomodulatory activity. This implies a dual role for hBD3 in antimicrobial activity and resolution of inflammation.
β-防御素是先天免疫反应中具有重要作用的抗菌肽。此外，β-防御素还可以趋化参与适应性免疫的细胞。到目前为止，基于树突状细胞刺激的证据，人β防御素-3（hBD3）被认为具有促炎作用。我们在这里提供的证据表明，hBD3 在人和鼠原代 Mphi 中缺乏促炎活性。此外，在 LPS 存在的情况下，hBD3 和鼠同源物 Defb14（而不是 hBD2）有效抑制 TNF-α和 IL-6 的积累，暗示其具有抗炎功能。hBD3 还抑制 CD40/IFN-γ刺激的 Mphi，并且在体内，hBD3 显著降低 LPS 诱导的血清 TNF-α水平。最近的研究表明 hBD3 与黑皮质素受体结合，但我们提供的证据表明这些受体不参与 hBD3 的免疫调节活性。这意味着 hBD3 在抗菌活性和炎症消退中具有双重作用。
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