Sodhi Ajit, Sharma Rajesh Kumar, Batra H V
School of Biotechnology, Banaras Hindu University, Varanasi, UP, India.
Immunol Lett. 2005 Jul 15;99(2):146-52. doi: 10.1016/j.imlet.2005.02.009. Epub 2005 Mar 16.
Yersinia antigenic proteins LcrV and YopB are translocators of effector Yops in type III secretion system. Recently, we have reported that rLcrV and rYopB inhibit the production of TNF-alpha, IFN-gamma, and IL-12 in murine peritoneal macrophages. It was also demonstrated that IL-10 and TLR2 signaling pathways and inhibition of MAPK cascade is involved in rLcrV- and rYopB-induced immunomodulation. In the present study, it is reported that rLcrV and rYopB inhibited the LPS-induced production of IL-1beta in macrophages. Pretreatment of macrophages with rLcrV and rYopB also inhibited the LPS-induced transcription of IL-6 but not of GM-CSF. However, the transcription of chemokines like MCP-1, MIP-1alpha, MIP-1beta, and RANTES were inhibited by rLcrV and rYopB. Both proteins also affected the cytoskeleton and lipid rafts in macrophages. It is further observed that IL-10 antibodies abrogated the rLcrV- and rYopB-induced inhibition of IL-1beta production in LPS-treated macrophages. The data, therefore, suggests a possible role of IL-10 in rLcrV and rYopB mediated inhibition of LPS-induced production of IL-1beta in macrophages.
耶尔森菌抗原蛋白LcrV和YopB是III型分泌系统中效应蛋白Yops的转运蛋白。最近，我们报道了重组LcrV（rLcrV）和重组YopB（rYopB）可抑制小鼠腹腔巨噬细胞中肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）和白细胞介素-12（IL-12）的产生。还证实了IL-10和Toll样受体2（TLR2）信号通路以及丝裂原活化蛋白激酶（MAPK）级联反应的抑制参与了rLcrV和rYopB诱导的免疫调节。在本研究中，报道了rLcrV和rYopB抑制巨噬细胞中脂多糖（LPS）诱导的IL-1β产生。用rLcrV和rYopB预处理巨噬细胞也抑制了LPS诱导的IL-6转录，但不影响粒细胞-巨噬细胞集落刺激因子（GM-CSF）的转录。然而，趋化因子如单核细胞趋化蛋白-1（MCP-1）、巨噬细胞炎性蛋白-1α（MIP-1α）、巨噬细胞炎性蛋白-1β（MIP-1β）和调节激活正常T细胞表达和分泌因子（RANTES）的转录受到rLcrV和rYopB的抑制。这两种蛋白还影响巨噬细胞中的细胞骨架和脂筏。进一步观察到，IL-10抗体消除了rLcrV和rYopB对LPS处理的巨噬细胞中IL-1β产生的抑制作用。因此，数据表明IL-10在rLcrV和rYopB介导的抑制巨噬细胞中LPS诱导的IL-1β产生中可能发挥作用。
