Lasers in Medical Science

, Volume 26, Issue 5, pp 707–717 | Cite as

Low-level laser irradiation treatment reduces CCL2 expression in rat rheumatoid synovia via a chemokine signaling pathway

  • Lin Zhang
  • Jian Zhao
  • Noboru Kuboyama
  • Yoshimitsu AbikoEmail author
Original Article


Rheumatoid arthritis (RA) is an inflammatory joint disorder whose progression leads to the destruction of cartilage and bone. Although low-level laser irradiation (LLLI) is currently being evaluated for the treatment of RA, the molecular mechanisms underlying its effectiveness remain unclear. To investigate possible LLLI-mediated antiinflammatory effects, we utilized a collagen-induced arthritis (CIA) rat model and analyzed gene expression profiles in the synovial membranes of the knee joint. Total RNA was isolated from the synovial membrane tissue of the joints of untreated CIA rats or CIA rats treated with LLLI (830 nm Ga-Al-As diode), and gene expression profiles were analyzed by DNA microarray (41,000 rat genes), coupled with Ingenuity pathways analysis (IPA). DNA microarray analysis showed that CCL2 gene expression was increased in CIA tissue, and that LLLI treatment significantly decreased CIA-induced CCL2 mRNA levels. IPA revealed that chemokine signal pathways were involved in the activation of CCL2 production. These microarray data were further validated using real-time PCR and reverse transcription PCR. Immunohistochemistry confirmed that CCL2 production was decreased in CIA rats treated with LLLI. These findings suggest that decreased CCL2 expression may be one of the mechanisms involved in LLLI-mediated RA inflammation reduction.


Rheumatoid arthritis Rat joint CCL2 DNA microarray Low-level laser irradiation 



This study was supported in part by the “Academic Frontier” project for private Universities, a matching fund subsidy from the Ministry of Education, Culture, Sports, Science and Technology 2007–2011, and by a Grant-in-Aid for Scientific Research from the Japanese Society for the Promotion of Science (B21390497).


  1. 1.
    Firestein GS (2003) Evolving concepts of rheumatoid arthritis. Nature 423:356–361PubMedCrossRefGoogle Scholar
  2. 2.
    Gravallese EM (2002) Bone destruction in arthritis. Ann Rheum Dis 61(suppl 2):ii84–ii86PubMedGoogle Scholar
  3. 3.
    Dayer JM (2002) The saga of the discovery of IL-1 and TNF and their specific inhibitors in the pathogenesis and treatment of rheumatoid arthritis. J Bone Spine 59:123–132CrossRefGoogle Scholar
  4. 4.
    Trentham DE, Townes AS, Kang AH (1977) Autoimmunity to type II collagen an experimental model of arthritis. J Exp Med 146:857–868PubMedCrossRefGoogle Scholar
  5. 5.
    Trentham DE (1998) Collagen arthritis in rats, arthritogenic lymphokines and other aspects. Int Rev Immunol 4:25–33CrossRefGoogle Scholar
  6. 6.
    Brosseau L, Welch V, Wells G, Tugwell P, de Bie R, Gam A, Harman K, Shea B, Morin M (2000) Low level laser therapy for osteoarthritis and rheumatoid arthritis: a metaanalysis. J Rheumatol 27:1961–1969PubMedGoogle Scholar
  7. 7.
    Lockhart DJ, Dong H, Byrne MC, Follettie MT, Gallo MV, Chee MS et al (1996) Expression monitoring by hybridization to high-density oligonucleotide arrays. Nat Biotechnol 14:1675–1680PubMedCrossRefGoogle Scholar
  8. 8.
    Noordewier MO, Warren PV (2001) Gene expression microarrays and the integration of biological knowledge. Trends Biotechnol 19:412–415PubMedCrossRefGoogle Scholar
  9. 9.
    Li CJ, Li RW, Wang YH, Elsasser TH (2007) Pathway analysis identifies perturbation of genetic networks induced by butyrate in a bovine kidney epithelial cell line. Funct Integr Genomics 7:193–205PubMedCrossRefGoogle Scholar
  10. 10.
    Huffnagle GB, Strieter RM, Standiford TJ, McDonald RA, Burdick MD, Kunkel SL et al (1995) The role of monocyte chemotactic protein-1 (MCP-1) in the recruitment of monocytes and CD4+ T cells during a pulmonary Cryptococcus neoformans infection. J Immunol 155:4790–4797PubMedGoogle Scholar
  11. 11.
    Harigai M, Hara M, Yoshimura T, Leonard EJ, Inoue K, Kashiwazaki S (1993) Monocyte chemoattractant protein-1 (MCP-1) in inflammatory joint diseases and its involvement in the cytokine network of rheumatoid synovium. Clin Immunol Immunopathol 69:83–91PubMedCrossRefGoogle Scholar
  12. 12.
    Ellingsen T, Buus A, Stengaard-Pedersen K (2001) Plasma monocyte chemoattractant protein 1 is a marker for joint inflammation in rheumatoid arthritis. J Rheumatol 28:41–46PubMedGoogle Scholar
  13. 13.
    Shahrara S, Proudfoot AE, Park CC, Volin MV, Haines GK, Woods JM et al (2008) Inhibition of monocyte chemoattractant protein-1 ameliorates rat adjuvant-induced arthritis. J Immunol 180:3447–3456PubMedGoogle Scholar
  14. 14.
    Patel DD, Zachariah JP, Whichard LP (2001) CXCR3 and CCR5 ligands in rheumatoid arthritis synovium. Clin Immunol 98:39–45PubMedCrossRefGoogle Scholar
  15. 15.
    Zapico I, Coto E, Rodriguez A, Alvarez C, Torre JC, Alvarez V (2000) CCR5 (chemokine receptor-5) DNA-polymorphism influences the severity of rheumatoid arthritis. Genes Immun 4:288–289CrossRefGoogle Scholar

Copyright information

© Springer-Verlag London Ltd 2011

Authors and Affiliations

  • Lin Zhang
    • 1
  • Jian Zhao
    • 1
  • Noboru Kuboyama
    • 2
  • Yoshimitsu Abiko
    • 1
    Email author
  1. 1.Department of Biochemistry and Molecular BiologyNihon University School of Dentistry at MatsudoMatsudoJapan
  2. 2.Department of Oral Molecular PharmacologyNihon University School of Dentistry at MatsudoMatsudoJapan

Personalised recommendations