炎症・再生
Online ISSN : 1880-5795
Print ISSN : 1346-8022
ISSN-L : 1346-8022
23 巻 , 4 号
選択された号の論文の7件中1~7を表示しています
Editorial
Review Article
  • 鈴木 賢一, 北川 誠一
    2003 年 23 巻 4 号 p. 204-210
    発行日: 2003年
    公開日: 2006/12/01
    ジャーナル フリー
    Interleukin-1 (IL-1) plays a central role in the immune and inflammatory responses, and activates various types of cells, including human neutrophils. IL-1β exerts its effects through IL-1 receptor type I, and activates NF-κB and mitogen-activated protein kinase (MAPK) cascades. In human neutrophils, it was found that the MKK3/6-p38 MAPK cascade was selectively activated by IL-1β, and p38 MAPK activation mediated IL-1β-induced superoxide (O2-) release and up-regulation of CD11b (β2 integrin) and CD15 (a ligand for P-selectin). Our recent studies also show that stimulation of human neutrophils with various cytokines, including granulocyte colonystimulating factor, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-α, results in cytokine-specific activation of distinct MAPK subtype cascades, and that extracellular signal-regulated kinase as well as p38 MAPK mediates cytokine-induced O2- release and adherence. In this review, we discuss the signaling pathways activated by IL-1β and the role of MAPK subtype cascades and JAK-STAT pathway in activation of human neutrophils by inflammatory cytokines.
  • 審良 静男
    2003 年 23 巻 4 号 p. 211-217
    発行日: 2003年
    公開日: 2006/12/01
    ジャーナル フリー
    Toll-like receptors (TLRs) play a critical role in the detection of invading pathogens and subsequent immune response against them. Individual TLRs recognize distinct microbial components. The TLR is a type 1 transmembrane receptor that is composed of an extracellular leucine-rich repeat (LRR) domain and cytoplasmic domain homologous to that of the IL-1R family. Therefore, TLR and IL-1R family use the same signaling molecules. Cytokine production in response to each TLR ligand is completely abolished in MyD88-deficient cells, indicating that MyD88 is an essential signaling molecule shared among IL-1R/Toll family. However, accumulating evidence indicates that differential utilization of adaptors including MyD88, TIRAP, and TRIF may activate overlapping as well as distinct signaling pathways, and finally give rise to distinct biological effects exerted by individual TLR family.
Mini Review
  • 村松 慎一, 王 立軍, 池口 邦彦, 藤本 健一, 永田 三保子, 中野 今治, 小澤 敬也
    2003 年 23 巻 4 号 p. 218-222
    発行日: 2003年
    公開日: 2006/12/01
    ジャーナル フリー
    Motor symptoms in Parkinson's disease (PD) result from severe decreases in the dopamine (DA) content of the striatum, secondary to progressive loss of nigrostriatal dopaminergic neurons. One potential strategy for treating advanced PD is the local production of DA in the striatum by restoring the enzymes for DA synthesis. Injection of recombinant adeno-associated viral (rAAV) vectors expressing enzymes necessary for efficient DA synthesis into the unilateral putamen of Parkinsonian monkeys resulted in amelioration of motor dysfunction with robust transgene expression and elevated DA synthesis in the treated putamen. An alternative strategy for gene therapy of PD is to relieve or reverse the ongoing degenerative processes by delivering genes for molecules that would block further dopaminergic cell loss. Sustained expression of a glial cell line-derived neurotrophic factor gene in the striatum rescued nigral neurons and led to functional recovery in a rat model of PD, even when treatment was delayed until after the onset of progressive degeneration. Gene therapy using rAAV vectors represents a novel and feasible protocol for the treatment of PD.
  • 岩渕 和久, 小林 俊秀, 石井 久美子, 牧野 麻美, 加賀 直子, 村山 季美枝, 長岡 功
    2003 年 23 巻 4 号 p. 223-230
    発行日: 2003年
    公開日: 2006/12/01
    ジャーナル フリー
    Lactosylceramide (LacCer), which is neutral glycosphingolipid and also known as CDw17, mediates superoxide production from neutrophils. Microorganisms such as gram-negative and -positive bacteria and fungi can bind to LacCer. Neutrophils thus appear to contribute to phagocytosis and superoxide generation. Treatment of neutrophils with anti-LacCer antibodies induced superoxide generation from the cells, which was blocked by PP1, wortomannin, SB203580 and H7, suggesting involvement of Src kinase, PI3 kinase, p38-MAP kinase, and protein kinase C, respectively. Upon exposure to dimethylsulfoxide (DMSO) that triggered differentiation into neutrophil lineage, promyelocytic leukemia HL-60 cells acquired the ability to generate superoxide, whilie exhibiting little response to the antibodies, if any. Density gradient centrifugation revealed that LacCer and a Src kinase Lyn were recovered in detergent-insoluble membrane (DIM) of neutrophils and HL-60 cells. However, LacCer was associated with Lyn in neutrophils but not HL-60 cells. Anti-LacCer antibody T5A7 phosphorylated Lyn molecules in neutrophil DIM. Taken together, these above data suggest that neutrophils are characterized by the presence of cell surface LacCer-enriched glycosignaling domain coupled with Lyn, and that the ligand binding to LacCer induces the activation of Lyn/PI3K/p38 MAPK/protein kinase C signal transduction pathway. The association of Lyn with LacCer seems to be a key for LacCer-mediated activation of Lyn, leading to superoxide generation by neutrophils.
  • 橋本 篤, 河野 静, 遠藤 平仁, 近藤 啓文
    2003 年 23 巻 4 号 p. 231-236
    発行日: 2003年
    公開日: 2006/12/01
    ジャーナル フリー
    Leukotriene B4(LTB4) is a metabolite of arachidonic acid and potent chemotactic factors and activators of neutrophils and macrophages. Overproduction of LTB4 is involved in various inflammatory diseases such as rheumatoid arthritis(RA).
    To evaluate the role of LTB4 receptors in inflammatory arthritis we measured the two types of LTB4 receptors, BLT1 and BLT2. BLT1 and BLT2 mRNA were detected by reverse transcription polymerase chain reaction (RTPCR) / Southern blot hybridization and in situ hybridization in synovial tissues of 40 patients with RA and 10 patients with OA(Osteoarthritis). The low affinity receptor BLT2 showed stronger expression than the high affinity receptor BLT1 in actively inflamed synovial tissues from patients with RA. Synovial macrophage, fibroblast-like cells and lymphocytes detected BLT2 mRNA in RA synovial tissues containing active inflammation. Then synovial fluid infiltrated leukocytes dominantly expressed BLT1 mRNA in RA.
    These results indicate that LTB4 effects via BLT1 on synovial fluid leukocytes and via BLT2 on synovial macrophages, fibroblast-like cells and lymphocytes in RA synovial tissues. No BLT antagonists are yet available for clinical use including RA therapy. More further works are needed about lipoxygenase system and inflammatory arthritis such as RA.
  • 湯本 健司, 辻 邦和, 二藤 彰, 野田 政樹
    2003 年 23 巻 4 号 p. 237-239
    発行日: 2003年
    公開日: 2006/12/01
    ジャーナル フリー
    We review here regarding the observations that expression of osteopontin (OPN) was enhanced in the joints of rheumatoid arthritis patients. OPN in arthritic joints had not been clear previously. We published in 2002 that joint destruction in the arthritis model induced by a mixture of anti-type II collagen monoclonal antibodies and LPS (mAbs/LPS) injection was suppressed in the OPN-deficient mice. OPN is a phosphorylated glycoprotein interacts with integrins and CD44, promote the cell attachment and migration. OPN is highly expressed in bone, kidney and ovary and also produced by osteoclasts, endotherial cells, activated T cells and macrophages. One of the functions of OPN in the inflammatory condition is to bring inflammatory cells to the sites of injury and OPN is also a survival factor for the endotherial cells and enhances angiogenesis by promoting the vascular tube formation. Infiltration of inflammatory cells and angiogenesis in synovium in the arthritis model was suppressed in OPN-deficient mice. Additionally, apoptosis of chondrocytes in articular cartilage was reduced and destruction of articular cartilage was suppressed in the arthritis model in OPN-deficient mice. These data suggested that OPN might be a new target for the treatment of rheumatoid arthritis.
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