Tài liệu Báo cáo khoa học: Molecular aspects of rheumatoid arthritis: chemokines in the joints of

MINIREVIEW

Molecular aspects of rheumatoid arthritis: chemokines

in the joints of patients

Takuji Iwamoto1,2, Hiroshi Okamoto1

, Yoshiaki Toyama2 and Shigeki Momohara1

1 Institute of Rheumatology, Tokyo Women’s Medical University, Japan

2 Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, Japan

Introduction

Rheumatoid arthritis (RA) is a chronic systemic inflam￾matory disease that occurs in about 1% of the popula￾tion. The inflammatory process is characterized by

infiltration of inflammatory cells into the joints, leading

to the proliferation of fibroblast-like synoviocytes (FLS)

and the destruction of cartilage and bone. In RA syno￾vial tissue, the infiltrating cells consist of macrophages,

T cells, B cells, plasma cells, neutrophils, mast cells,

dendritic cells and natural killer cells [1]. Migration of

leukocytes into the synovium is a regulated multistep

process involving interactions between leukocytes and

endothelial cells and cellular adhesion molecules, as well

as between leukocytes and chemokines and chemokine

receptors [2]. Chemokines are small, chemoattractant

cytokines that play key roles in the accumulation of

inflammatory cells at the site of inflammation. There￾fore, chemokines and chemokine receptors are consid￾ered to be therapeutic targets in several chronic

Keywords

chemokine receptors; chemokines;

monocyte chemoattractant protein-4

(MCP-4) ⁄ CCL13; pulmonary and activation￾regulated chemokine (PARC)/CCL18;

rheumatoid arthritis (RA)

Correspondence

H. Okamoto, Institute of Rheumatology,

Tokyo Women’s Medical University, 10-22

Kawada-cho, Shinjuku, Tokyo 162-0054,

Japan

Fax: +81 3 5269 1726

Tel: +81 3 5269 1725

E-mail: [email protected]

(Received 14 March 2008, revised 27 May

2008, accepted 27 June 2008)

doi:10.1111/j.1742-4658.2008.06580.x

Rheumatoid arthritis (RA) is a chronic symmetric polyarticular joint dis￾ease that primarily affects the small joints of the hands and feet. The

inflammatory process is characterized by infiltration of inflammatory cells

into the joints, leading to proliferation of synoviocytes and destruction of

cartilage and bone. In RA synovial tissue, the infiltrating cells such as

macrophages, T cells, B cells and dendritic cells play important role in the

pathogenesis of RA. Migration of leukocytes into the synovium is a regu￾lated multi-step process, involving interactions between leukocytes and

endothelial cells, cellular adhesion molecules, as well as chemokines and

chemokine receptors. Chemokines are small, chemoattractant cytokines

which play key roles in the accumulation of inflammatory cells at the site

of inflammation. It is known that synovial tissue and synovial fluid from

RA patients contain increased concentrations of several chemokines, such

as monocyte chemoattractant protein-4 (MCP-4)⁄ CCL13, pulmonary and

activation-regulated chemokine (PARC)⁄ CCL18, monokine induced

by interferon-c (Mig)⁄ CXCL9, stromal cell-derived factor 1 (SDF-1)⁄

CXCL12, monocyte chemotactic protein 1 (MCP-1)⁄ CCL2, macrophage

inflammatory protein 1a (MIP-1a)⁄ CCL3, and Fractalkine ⁄ CXC3CL1.

Therefore, chemokines and chemokine-receptors are considered to be

important molecules in RA pathology.

Abbreviations

CCL3L1, CCL3-like 1; GROa, growth-related oncogene a; IFN-c, interferon-c; IL, interleukin; IP-10, interferon-c-inducible protein-10; MAPK,

mitogen-activated protein kinase; MCP, monocyte chemoattractant protein; Mig, monokine induced by interferon-c; MIP, macrophage

inflammatory protein; MMP, matrix metalloproteinase; OA, osteoarthritis; PARC, pulmonary and activation-regulated chemokine;

RA, rheumatoid arthritis; RANTES, regulated on activation, normal, T-cell expressed, and secreted; SDF, stromal cell-derived factor;

TNF-a, tumor necrosis factor-a.

4448 FEBS Journal 275 (2008) 4448–4455 ª 2008 The Authors Journal compilation ª 2008 FEBS