Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj 11942, Saudi Arabia.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.
Int J Mol Sci. 2021 Jun 25;22(13):6833. doi: 10.3390/ijms22136833.
Alveolar macrophages are the first line of defense against intruding pathogens and play a critical role in cancer immunology. The Toll-like receptor (TLR) family mediates an important role in recognizing and mounting an immune response against intruding microbes. TLR-9 is a member of the intracellular TLR family, which recognizes unmethylated CG motifs from the prokaryotic genome. Upon its activation, TLR-9 triggers downstream of the MyD-88-dependent transcriptional activation of NF-κB, and subsequently results in abundant inflammatory cytokines expression that induces a profound inflammatory milieu. The present exploratory investigation aimed at elucidating the potency of schizophyllan for entrapping ODN 1826 (SPG-ODN 1826)-mediated stimulation of TLR-9 in provoking an inflammatory-type response in murine alveolar macrophages. Schizophyllan (SPG), a representative of the β-glucan family, was used in the present study as a nanovehicle for endosomal trafficking of CpG ODN 1826. TEM analysis of SPG-ODN 1826 nanovehicles revealed that the prepared nanovehicles are spherical and have an average size of about 100 nm. Interestingly, SPG-ODN 1826 nanovehicles were competent in delivering their therapeutic payload within endosomes of murine alveolar macrophage (J774A.1) cells. Exposure of these nanovehicles within LPS stimulated J774A.1, resulted in a significant provocation of reactive oxygen species (ROS) ( < 0.01) in comparison to CpG ODN 1826 alone. Moreover, the formulated nanovehicles succeeded in generating a profound Th1-based cytokine profile constituted by enhanced expression of IFN-γ ( < 0.001) and IL-1β ( < 0.001) inflammatory cytokines. These findings clearly indicated the immunostimulatory potential of SPG-ODN 1826 nanovehicles for inducing the Th1-type phenotype, which would certainly assist in skewing M2 phenotype into the much-desired M1 type during lung cancer.
肺泡巨噬细胞是抵御入侵病原体的第一道防线，在癌症免疫学中起着关键作用。Toll 样受体 (TLR) 家族在识别和引发针对入侵微生物的免疫反应方面发挥着重要作用。TLR-9 是细胞内 TLR 家族的成员，它识别原核基因组中未甲基化的 CG 基序。激活后，TLR-9 触发 MyD-88 依赖性转录激活 NF-κB 的下游，随后导致大量炎症细胞因子的表达，诱导强烈的炎症微环境。本探索性研究旨在阐明裂褶多糖（SPG）捕获 ODN 1826（SPG-ODN 1826）介导的 TLR-9 刺激，在诱导鼠肺泡巨噬细胞炎症型反应中的效力。裂褶多糖 (SPG) 是β-葡聚糖家族的代表，在本研究中用作 CpG ODN 1826 的内体转运的纳米载体。SPG-ODN 1826 纳米载体的 TEM 分析表明，所制备的纳米载体呈球形，平均粒径约为 100nm。有趣的是，SPG-ODN 1826 纳米载体能够在 LPS 刺激的 J774A.1 肺泡巨噬细胞内将其治疗性有效载荷递送至内体。与单独的 CpG ODN 1826 相比，将这些纳米载体暴露于 LPS 刺激的 J774A.1 中会导致活性氧 (ROS) 的显著激发（<0.01）。此外，所构建的纳米载体成功地产生了深刻的 Th1 为基础的细胞因子谱，由 IFN-γ（<0.001）和 IL-1β（<0.001）炎症细胞因子的表达增强组成。这些发现清楚地表明了 SPG-ODN 1826 纳米载体诱导 Th1 型表型的免疫刺激潜力，这肯定有助于在肺癌期间将 M2 表型偏向所需的 M1 型。
