Blood levels of heat shock protein (HSP27) and natural IgG auto-antibodies to HSP27 (AAbs) are higher in healthy controls compared to cardiovascular disease patients. Vaccination of mice with recombinant HSP25 (rHSP25, murine ortholog of human rHSP27) increased AAb levels, attenuated atherogenesis and reduced plaque inflammation and cholesterol content. We sought to determine if the HSP27 immune complex (IC) altered MΦ inflammation signaling (Toll Like Receptor 4; TLR4), and scavenger receptors involved in cholesterol uptake (SR-AI, CD-36). Combining a validated polyclonal IgG anti-HSP27 antibody (PAb) with rHSP27 enhanced binding to THP-1 MΦ cell membranes and activation of NF-κB signaling via TLR4, competing away LPS and effecting an anti-inflammatory cytokine profile. Similarly, adding the PAb with rHSP27 enhanced binding to SR-AI and CD-36, as well as lowered oxLDL binding in HEK293 cells separately transfected with SR-AI and CD-36, or THP-1 MΦ. Finally, the PAb enhanced the uptake and internalization of rHSP27 in THP-1 MΦ. Thus, the HSP27 IC potentiates HSP27 cell membrane signaling with receptors involved in modulating inflammation and cholesterol uptake, as well as HSP27 internalization. Going forward, we will explore HSP27 Immune Complex Altered Signaling and Transport (ICAST) as a new anti-inflammatory therapeutic strategy in vivo.

中文翻译：

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热休克蛋白27免疫复合物信号传导和转运改变（ICAST）：减轻炎症的新机制。

与心血管疾病患者相比，健康对照者的血液中热休克蛋白（HSP27）和天然的针对HSP27的IgG自身抗体的水平更高（AAbs）。用重组HSP25（rHSP25，人rHSP27的鼠类同源物）对小鼠进行疫苗接种可提高Abb水平，减缓动脉粥样硬化形成，减少斑块炎症和胆固醇含量。我们试图确定HSP27免疫复合物（IC）是否改变了MΦ炎症信号（Toll样受体4； TLR4）以及参与胆固醇吸收的清道夫受体（SR-AI，CD-36）。将经过验证的多克隆IgG抗HSP27抗体（PAb）与rHSP27结合，可增强与THP-1MΦ细胞膜的结合，并通过TLR4激活NF-κB信号传导，与LPS竞争，从而影响抗炎细胞因子的表达。同样，添加带有rHSP27的PAb可增强与SR-AI和CD-36的结合，以及分别用SR-AI和CD-36或THP-1MΦ转染的HEK293细胞中的oxLDL结合水平降低。最后，PAb增强了THP-1MΦ中rHSP27的摄取和内在化。因此，HSP27 IC通过参与调节炎症和胆固醇摄取以及HSP27内在化的受体来增强HSP27细胞膜信号传导。展望未来，我们将探索HSP27免疫复合物信号传导和转运改变（ICAST）作为体内新的抗炎治疗策略。