Reduction of CCL-2 in Rheumatoid Arthritis Rats by Laser Irradiation

Objectives: Rheumatoid arthritis (RA) is an inflammatory joint disorder, the progressions of which leads to the destruction of cartilage and bone. Low-level laser irradiation (LLLI) is being evaluated for the treatment of RA, however, the molecular mechanism underlying the effectiveness of LLLI to RA is unclear. Macrophage/monocyte infiltration is essential to the development of rheumatoid arthritis. CCL2 plays an important role in recruiting macrophage/monocytes in joint inflammation. The objective of this study was to delineate a mechanism whereby LLLI reduced inflammation of RA through the modulation of CCL2 gene expression in joints of collagen-induced RA (CIA) rats.

Methods: Total RNA was isolated from synovial membrane tissue of CIA rat joints with or without treatment of 830 nm Ga-Al-As diode LLLI, and gene expression profiles were analyzed by DNA microarray (rat 41,000 genes), Ingenuity Pathway Analysis (IPA). Altered mRNA levels in GeneChip results were confirmed by real-time PCR and reverse transcription polymerase chain reaction (RT-PCR). Immunohistochemical examination and quantitative micro–computed tomography (micro-CT) imaging analysis were carried out.

Results: DNA microarray analysis showed that CCL2 gene expression was increased in CIA tissue, and LLLI significantly decreased CIA induced CCL2 mRNA level. IPA analysis revealed that chemokine signal pathway was involved in activation of CCL2 production. Real-time PCR and RT-PCR data were consistent with the microarray data. Immunohistochemistry confirmed that CCL2 production was decreased in CIA rats by LLLI. Quantitative micro-CT imaging analysis showed that LLLI suppressed bone/cartilage destruction observed in CIA rat joints.

Conclusion: These finding suggest that decreased CCL2 gene expression may be one of mechanisms in reduction of inflammation in RA by LLLI.