Photodynamic therapy mediates innate immune responses via fibroblast–macrophage interactions

Abstract

Antibacterial photodynamic therapy (PDT) has come to attract attention as an alternative therapy for drug-resistant bacteria. Recent reports revealed that antibacterial PDT induces innate immune response and stimulates abundant cytokine secretion as a part of inflammatory responses. However, the underlying mechanism how antibacterial PDT interacts with immune cells responsible for cytokine secretion has not been well outlined. In this study, we aimed to clarify the difference in gene expression and cytokine secretion between combined culture of fibroblasts and macrophages and their independent cultures. SCRC-1008, mouse fibroblast cell line and J774, mouse macrophage-like cell line were co-cultured and PDT treatments with different parameters were carried out. After various incubation periods (1-24 h), cells and culture medium were collected, and mRNA and protein levels for cytokines were measured using real-time PCR and ELISA, respectively. Our results showed that fibroblasts and macrophages interact with each other to mediate the immune response. We propose that fibroblasts initially respond to PDT by expressing Hspa1b, which regulates the NF-κB pathway via Tlr2 and Tlr4. Activation of the NF-κB pathway then results in an enhanced secretion of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) and neutrophil chemoattractant MIP-2 and KC from macrophages.

The impact of antimicrobial photodynamic therapy on peri-implant disease: What mechanisms are involved in this novel treatment?

“…Consistent with the mechanism of action of this therapy [124], the results revealed high TNF-␣ expression; however, the expression levels of IL-1 and IL-6 in the aPDT group were lower than and similar to those in the untreated group, respectively [123]. During the delayed phase reaction, neutrophil chemo-attractants and IL-1b are the factors regulating neutrophil migration [125]. With regard to peri-implantitis, this disease involves the destruction of alveolar bone, which leads to implant loss.…”

Proteomics analysis reveals heat shock proteins involved in caprine parainfluenza virus type 3 infection

“…However, fibroblasts and macrophages interact with each other to mediate the immune response. Activation of the NF-κB pathway then results to in enhanced secretion of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) and neutrophil chemoattractant MIP-2 and Cxcl1 from macrophages [36]. This evidence indicates that HSPA1B may be associated with the proliferation of CPIV3 in MDBK cells through an ability to interact with key components of the NF-κB pathway, moreover, those involved in innate immunity, but the detailed mechanism remains unknown.…”

A Novel Prospective Study Assessing the Combination of Photodynamic Therapy and Proton Radiation Therapy: Safety and Outcomes When Treating Malignant Pleural Mesothelioma

“…There are theoretical reasons to think that PDT and PT may be synergistic. PDT promotes the microenvironment to be more conducive to immunologic effect, can lead to an inflammatory reaction that can evoke a host anti‐tumor immune response, and can lead to immunogenic cell death . Recent reports have suggested that proton and heavy ion therapy may stimulate the immune system to a greater degree than photon therapy .…”