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상지가 콜라겐 유발 관절염 랫트에 미치는 영향 - 배액림프절의 면역세포 발현 -

Effects of Mori Ramulus on Collagen-induced Arthritis Rat - Expression of Immunocells in Draining Lymph Node -

구세광|서영배|노성수
한의병리학회 (The Society of Pathology in Korean Medicine)|2009.10|동의생리병리학회지 (Journal of Physiology & Pathology in Korean Medicine)|제23권 제5호|pp. 1106-1115

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참고문헌

키워드

rheumatoid arthritismori ramuluscollagen-induced arthritisdraining lymph node(DLN)
주제분류한의학

초록

Mori Ramulus has multiple applications in Korean traditional medicine prescription because it has antioxidant and anti-inflammatory effects by reducing macrophage activities. Yet, no studies on the anti-arthritic activity of EMR (extract of Mori Ramulus) have been reported in vitro and in vivo. Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic inflammation characterized by hyperplasia of synovial cells in affected joints, which ultimately leads to the destruction of cartilage and bone. Because collagen-induced arthritis (CIA) is similar to RA in pathological symptoms and immune reactions, there have been several reports concerning RA using CIA mouse model. Here, we investigated the effects of Mori Ramulus on RA using CIA mice. The importance of CD4+ Th1 cells in RA progress was previously indicated and studies further showed that Th17 cells play a prime role in severity of disease. Accordingly, the present study was focused on CIA associated with CD4+ Th1 cells and Th17 cells. DBA/1OlaHsd mice were immunized with bovine type Ⅱ collagen (CⅡ). After a second collagen immunization, mice were treated with EMR once a day for 4 weeks. The severity of arthritis within the paw joints was evaluated by histological assessment of cartilage destruction and pannus formation. Immune cells in peripheral blood mononuclear cells (PBMC), draining lymph node (DLN) and paw joints, cytokine production and gene expression were assessed from CIA mouse using ELISA, FACS and real-time PCR analysis. Administration of EMR significantly suppressed the progression of CIA and inhibited the production of TNF-α, IL-6 and IL-17 in the serum. The erosion of cartilage was dramatically reduced in mouse knees after treatment with EMR. In conclusion, our results demonstrate that EMR significantly suppressed the progression of CIA and that this action was mediated by the decreased production of TNF-α, IL-6, IL-17 and collagen Ⅱ-specific antibody in the serum. EMR suppressed Th17 cells and reduced level of IL-6 via B cell suppression, and thus, the levels of autoantibodies produced from B cells were decreased. Furthermore, EMR suppressed NKT cells which directly stimulate B cells and develop imbalance of Th1/Th2 cell. Oral administration of EMR (100 ㎎/㎏ or 200 ㎎/㎏) significantly suppressed the progression of CIA, which is comparable to that of methotrexate (MTX, 0.3 ㎎/㎏) used as a positive control. We are currently studying the mechanism underlying the therapeutic role for EMR in CIA mice.

Abstract

Mori Ramulus has multiple applications in Korean traditional medicine prescription because it has antioxidant and anti-inflammatory effects by reducing macrophage activities. Yet, no studies on the anti-arthritic activity of EMR (extract of Mori Ramulus) have been reported in vitro and in vivo. Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic inflammation characterized by hyperplasia of synovial cells in affected joints, which ultimately leads to the destruction of cartilage and bone. Because collagen-induced arthritis (CIA) is similar to RA in pathological symptoms and immune reactions, there have been several reports concerning RA using CIA mouse model. Here, we investigated the effects of Mori Ramulus on RA using CIA mice. The importance of CD4+ Th1 cells in RA progress was previously indicated and studies further showed that Th17 cells play a prime role in severity of disease. Accordingly, the present study was focused on CIA associated with CD4+ Th1 cells and Th17 cells. DBA/1OlaHsd mice were immunized with bovine type Ⅱ collagen (CⅡ). After a second collagen immunization, mice were treated with EMR once a day for 4 weeks. The severity of arthritis within the paw joints was evaluated by histological assessment of cartilage destruction and pannus formation. Immune cells in peripheral blood mononuclear cells (PBMC), draining lymph node (DLN) and paw joints, cytokine production and gene expression were assessed from CIA mouse using ELISA, FACS and real-time PCR analysis. Administration of EMR significantly suppressed the progression of CIA and inhibited the production of TNF-α, IL-6 and IL-17 in the serum. The erosion of cartilage was dramatically reduced in mouse knees after treatment with EMR. In conclusion, our results demonstrate that EMR significantly suppressed the progression of CIA and that this action was mediated by the decreased production of TNF-α, IL-6, IL-17 and collagen Ⅱ-specific antibody in the serum. EMR suppressed Th17 cells and reduced level of IL-6 via B cell suppression, and thus, the levels of autoantibodies produced from B cells were decreased. Furthermore, EMR suppressed NKT cells which directly stimulate B cells and develop imbalance of Th1/Th2 cell. Oral administration of EMR (100 ㎎/㎏ or 200 ㎎/㎏) significantly suppressed the progression of CIA, which is comparable to that of methotrexate (MTX, 0.3 ㎎/㎏) used as a positive control. We are currently studying the mechanism underlying the therapeutic role for EMR in CIA mice.

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