Efficacy of SPG-ODN 1826 Nanovehicles in Inducing M1 Phenotype through TLR-9 Activation in Murine Alveolar J774A.1 Cells: Plausible Nano-Immunotherapy for Lung Carcinoma

• Published in: International journal of molecular sciences 2021-07, Vol.22 (13), p.6833
• Main Authors: Aldawsari, Mohammed F., Alalaiwe, Ahmed, Khafagy, El-Sayed, Al Saqr, Ahmed, Alshahrani, Saad M., Alsulays, Bader B., Alshehri, Sultan, Abu Lila, Amr S., Danish Rizvi, Syed Mohd, Hegazy, Wael A. H.
• Format: Article
• Language: English
• Subjects: Alveoli; Antigens; CpG islands; Cytokines; Endosomes; Gene expression; Genomes; Glucan; Growth factors; IL-1β; Immune response; Immune system; Immunology; Immunostimulation; Immunotherapy; Inflammation; Lipopolysaccharides; Localization; Lung cancer; Lung carcinoma; Lymphocytes T; Macrophages; Medical prognosis; Microscopy; Morphology; NF-κB protein; Pathogens; Phenotypes; Population; Proteins; Reactive oxygen species; TLR9 protein; Toll-like receptors; Transcription activation; β-Glucan; γ-Interferon
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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) (p < 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 (p < 0.001) and IL-1β (p < 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.