Abstract

Low-level laser therapy (LLLT) has been used in the treatment of radiotherapy-induced oral mucositis and allergic rhinitis. However, the effects of LLLT on human monocyte polarization into M1 macrophages are unknown. To evaluate the effects of LLLT on M1-related cytokine and chemokine production and elucidate the mechanism, the human monocyte cell line THP-1 was treated with different doses of LLLT. The expression of M1-related cytokines and chemokines (CCL2, CXCL10, and TNF-α) was determined by ELISA and real-time PCR. LLLT-associated histone modifications were examined by chromatin immunoprecipitation (ChIP) assays. Mitochondrial involvement in the LLLT-induced M1-related cytokine expression was evaluated by quantitative real-time PCR. Flow cytometry was used to detect the cell surface markers for monocyte polarization. The results showed that LLLT (660 nm) significantly enhanced M1-related cytokine and chemokine expression in mRNA and protein levels. Mitochondrial copy number and mRNA levels of complex I-V protein were increased by LLLT (1 J/cm2). Activation of M1 polarization was concomitant with histone modification at TNF-α gene locus and IP-10 gene promoter area. This study indicates that LLLT (660 nm) enhanced M1-related cytokine and chemokine expression via mitochondrial biogenesis and histone modification, which may be a potent immune-enhancing agent for the treatment of allergic diseases.

Highlights

  • Both innate and adaptive immune responses are, in every way, affected by polarization with cytokines

  • Because different types of lasers have been used for the treatment of Th2-dominant disease, we evaluate the influence of level laser therapy (LLLT) on monocyte polarization in this study

  • IFN-r polarization, occurring through either classical or M1 activation, programs monocytes for phagocytosis, tumor resistance, and allergy suppression

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Summary

Introduction

Both innate and adaptive immune responses are, in every way, affected by polarization with cytokines. The expression of costimulatory molecules and chemokines, as well as the execution of effector programs, is affected in monocytes. T helper (Th) and Th2 polarization with IFN-r and IL-4 is well understood [1, 2]. IL-4 polarization, known as Mediators of Inflammation either alternative or M2a activation, stimulates wound recovery and parasite immunity responses. IFN-r polarization, which is referred to as either classical or M1 activation, is responsible for tumor resistance, intracellular killing, and IL12 production in monocytes [3]. M1 macrophages, which are activated by the classical pathway, are shown to be responsive to two signals: type 1 inflammatory cytokines and microbial products [4]

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