ALA‐PDT regulates macrophage M1 polarization via ERK/MAPK‐NLRP3 pathway to promote the early inflammatory response

Abstract

Background Photodynamic therapy (PDT) is a promising new approach to promote wound healing and its effectiveness has been demonstrated in both clinical and animal studies. Macrophages are the key cells in wound healing and inflammatory response. However, the mechanism of action of PDT on macrophages in promoting wound healing is still unclear. Methods In this study, RAW264.7 cells were used. We analyzed the expression levels of macrophage markers arginase 1 (Arg‐1), CD206, iNOS, CD86, and inflammatory factors IL‐6, TNF‐α, and IL‐1β by reverse transcription‐polymerase chain reaction and Western blot, Milliplex microtubule‐associated protein multiplex assay was performed to analyze the expression of inflammatory factors in the supernatant. Live cell Imaging System to observe the dynamic process of macrophage phagocytosis. Western blot was performed to observe the activation of extracellular signal‐regulated kinase/mitogen‐activated protein kinase (ERK/MAPK) and NOD‐like receptor protein 3 (NLRP3) inflammasome. Results 5‐Aminolevulinic acid (ALA)‐PDT increased the expression of M1 marker iNOS/CD86 and decreased the expression of Arg‐1/CD206 in RAW264.7 cells, while, proinflammatory factors IL‐6, TNF‐α, and IL‐1β expression was enhanced and macrophage phagocytosis was increased. We also found that these phenomena were associated with activation of the ERK/MAPK‐NLRP3 pathway. Conclusion ALA‐PDT promotes early inflammatory responses by regulating macrophage M1 polarization through the ERK/MAPK‐NLRP3 pathway. It also promotes macrophage phagocytosis.

Exosomes derived from TNF-α-treated bone marrow mesenchymal stem cells ameliorate myocardial infarction injury in mice

“…CD206 is a marker of M2 macrophage polarization, while iNOS is a marker of M1 polarization. 28 , 30 The results showed that MI led to the activation of macrophages in the infarcted tissue of mice, with an excessive imbalance between M1 and M2 polarization ( Figure 4a,b ). However, treatment with exosomes effectively promoted M2 polarization and suppressed M1 polarization ( Figure 4a,b ).…”

Hyperthermia promotes M1 polarization of macrophages via exosome-mediated HSPB8 transfer in triple negative breast cancer

“…The MAPK, TNF, and IL17 signaling pathways are classical inflammation-related pathways. Wang et al found that photodynamic therapy (PDT) could promote the polarization of M1 macrophage through the ERK/MAPK pathway [ 33 ].Also, the upregulation of MAPK phosphorylation level increased IL1, IL6, and TNF. The TNF pathway was a classic M1 type macrophage-related pathway.…”

Stimuli‐Mediated Macrophage Switching, Unraveling the Dynamics at the Nanoplatforms–Macrophage Interface

“…[158] Besides, photodynamic therapy (PDT) also triggers the expression of Arg-1, CD 206, iNOS, CD86, inflammatory factor IL-6, TNF-𝛼, and IL-𝛽1, MAPK/ERK pathway activation, and NODlike receptor protein 3 (NLRP3) inflammasome formation. [159] Histiocytic lymphoma cell line U-937, when subjected to light at 660, 820, 870, and 880 nm, results in the differential secretion of growth factors that affect fibroblast proliferation differentially. Another way to control macrophage polarization is the use of polarized light.…”