著者

藤原 永年 山上 博一 上田 定男 矢野 郁也 小林 和夫

出版者

一般社団法人 日本炎症・再生医学会

雑誌

炎症・再生 (ISSN:13468022)

巻号頁・発行日

vol.21, no.2, pp.133-138, 2001-03-28 (Released:2010-04-12)

参考文献数

20

---

Host responses against mycobacterial infection result in protection and granulomatous inflammation. Mycobacterial and host factors participate in the process. Mycobacteria are rich in lipids that may be involved in the pathogenesis. Host responses against the infection include both cell-mediated immune responses (host defense) and delayed-type hypersensitivity (expression of lesions) . A surface glycolipid of tubercle bacilli acts as both nonspecific inflammatory stimulus and specific T cell-dependent immunogen. Hosts produce chemokines, proinflammatory and immunoregulatory cytokines in response to glycolipids. The event leads to the recruitment of mononuclear cells, angiogenesis, and apoptosis. Mycobacterial glycolipid is a pleiotropic molecule, which induces pathogenesis and protective responses in the host. The pathogenesis of mycobacterial disease is a multistep process, involving a complex interaction between a range of bacterial and host factors.

著者

松村 潔 小林 茂夫

出版者

一般社団法人 日本炎症・再生医学会

雑誌

炎症・再生 (ISSN:13468022)

巻号頁・発行日

vol.21, no.3, pp.209-217, 2001-05-31 (Released:2010-04-12)

参考文献数

30

---

Prostaglandins play various roles in the brain under physiological as well as pathological conditions. This review summarizes our present knowledge about brain localization of two isoforms of cyclooxygenase, enzymes responsible for prostaglandin biosynthesis, and their possible functions. Cyclooxygenase-1 (COX-1) is con-stitutively expressed in microglia throughout the brain. Little is known about COX-1 function there. COX-1 is also abundantly expressed in the primary sensory neurons both at their cell bodies and at the central terminals in the medulla and spinal cord suggesting its involvement in sensory signal transmissions. COX-2 is constitutively expressed in telencephalic neurons in an activity-dependent manner. This neuronal expression of COX-2 was reported to be involved in the regulation of regional cerebral blood flow. On the other hand, some studies have reported that COX-2 might exert adverse actions after brain ischemia and in Alzheimer's disease. Under various infectious as well as inflammatory conditions, COX-2 is expressed in brain endothelial cells. We presented a large body of evidence that elevation of prostaglandin EZ in the brain and occurrence of fever during infection/inflammation are the consequences of this endothelial expression of COX-2. Thus, brain endothelial cells seem to transmit blood borne cytokine signals to brain by producing prostaglandin E2.

著者

李 頌華 王 如偉 田丸 直美 都 仁哉 岩崎 純夫 小林 裕太 奥西 秀樹

出版者

一般社団法人 日本炎症・再生医学会

雑誌

炎症・再生 (ISSN:13468022)

巻号頁・発行日

vol.24, no.1, pp.55-59, 2004 (Released:2006-10-25)

参考文献数

13

---

There has been considerable interest in traditional Chinese herbal therapy as a novel treatment for atopic dermatitis (AD). To investigate the efficacy and safety of formulas of traditional Chinese herbal medicine, Kujin-Plus, 94 AD patients received oral administration of the formula, Kujin-Plus I, containing 10 herbs, combined with a lotion, Kujin-Plus II, containing 7 herbs, and an ointment, Kujin-Plus III, containing 8 herbs as an open trial. The severity of the disease (clinical score; 0-4) and the severity of pruritus (pruritus score; 0-4) were judged by standardized scores. Both scores were significantly improved at the end of the treatment (p < 0.01;nonparametric test). The blood eosinophil ratio and serum IgE levels were high in AD patients and they were significantly reduced at the end of the treatment (p < 0.001). Of 94 AD patients with traditional Chinese herbal therapy, 32 were markedly improved, 59 were improved, 3 were slightly improved and none was ineffective. There was no remarkable evidence of renal or hepatic toxicity or another severe adverse effects. Thus, the present study confirmed that this herbal treatment is clinically efficacious on AD with a significant reduction in blood eosinophil ratio and serum IgE level.

著者

春日井 昇平

出版者

一般社団法人 日本炎症・再生医学会

雑誌

炎症・再生 (ISSN:13468022)

巻号頁・発行日

vol.23, no.1, pp.34-38, 2003 (Released:2006-12-01)

参考文献数

14

被引用文献数

4 3

---

Periodontal ligament (PDL) is a thin non-mineralized connective tissue between two mineralized tissues: alveolar bone and cementum. PDL keeps its function under enormous mechanical stress. In this article, I will introduce our studies characterizing the uniqueness of PDL and then discuss regeneration of periodontal tissue. S100A4 is a small Ca binding protein and we found high expression level of S100A4 in PDL. Histologically S100A4 localized on extracellular matrix and analysis of culture medium of PDL fibroblasts revealed secretion of S100A4 and recombinant S100A4 protein inhibited mineralization of osteoblastic culture. MC3T3-E1 cells (mouse osteoblastic cell line) expressed S100A4 at very low level and inhibition of S100A4 with a retroviral vector containing S100A4 antisense enhanced the mineralization of MC3T3-E1 cell culture. Finally, when PDL cells were exposed under mechanical stress in culture, expression level of S100A4 increased. These results indicate that S100A4 acts as a mineralization inhibitor in PDL and also bone; and that this protein plays a role in keeping its function under enormous mechanical stress. Although PDL is a non-mineralized tissue, it contains progenitors of osteoblasts and cementoblasts. Indeed, PDL is prerequisite for periodontal tissue regeneration. Application of guided tissue regeneration (GTR) and/or enamel matrix derivative (EMDOGAIN) promote periodontal tissue regeneration. Treatment with a dental implant, which is inserted to edentulous bone, is clinically acceptptable; however, a dental implant with PDL like a natural tooth would be more ideal.

著者

椛島 健治 成宮 周

出版者

一般社団法人 日本炎症・再生医学会

雑誌

炎症・再生 (ISSN:13468022)

巻号頁・発行日

vol.22, no.6, pp.535-541, 2002-11-30 (Released:2010-04-12)

参考文献数

12

---

One of the major risk factors triggering or worsening human inflammatory bowel disease (IBD) is the administration of non-steroidal anti-inflammatory drugs (NSAIDs) . Since NSAIDs share inhibition of the enzyme-cyclooxygenase (COX) that catalyzes production of prostanoids, some prostanoids are formed and negatively modulate the extension of IBD. We used mice deficient in prostaglandin (PG) E2 receptor EP1, EP2, EP3, and EP4, and examined the roles of prostaglandin E2 in DSS-induced colitis model. Among the PGE2 receptor-deficient mice, only EP4-deficient mice developed severe colitis with 3% DSS treatment, which induced only marginal colitis in wild-type mice. Conversely, administration of an EP 4-selective agonist (AE 1-734) to wild type mice ameliorated severe colitis normally induced with 7% DSS, while that of an EP 4 agonist, AE 3-208, suppressed recovery from colitis and induced significant proliferation of CD 4+ T cells. In vitro AE 3-208 enhanced and AE 1-734 suppressed the proliferation and Th 1 cytokine production of lamina propria mononuclear cells from the colon. DNA microarray analysis revealed elevated expression of genes associated with immune response and reduced expression of genes with mucosal repair and remodeling in the colon of EP 4-deficient mice. We conclude that EP 4 maintains intestinal homeostasis by keeping mucosal integrity and downregulating immune response.

著者

佐藤 靖史 安部 まゆみ

出版者

一般社団法人 日本炎症・再生医学会

雑誌

炎症・再生 (ISSN:13468022)

巻号頁・発行日

vol.22, no.3, pp.169-177, 2002-05-30 (Released:2010-04-12)

参考文献数

54

被引用文献数

1

---

Angiogenesis plays an essential role in a wide range of physiologic and pathologic states. Numerous factors are reported to be involved in angiogenesis. Among them, vascular endothelial growth factor (VEGF), a homodimer-secreted protein, is one of the most important factors. VEGF was initially termed vascular permeability factor (VPF) and was shown to induce vascular permeability, as well as to promote angiogenesis. There are three tyrosine kinase-type VEGF receptors, Fit-1 (VEGFR-1), KDR/Flk-1 (VEGFR-2), and Flt -4 (VEGFR-3) . Flt -1 and KDR/Flk-1 are expressed in vascular endothelial cells (ECs), whereas Flt -4 is preferentially expressed in lymphatic ECs. VEGF binds to Flt -1 and KDR/Flk-1, and to a membrane protein neuropilin-1 on ECs. Neuropilin-1 does not contain a tyrosine kinase domain, but is functionally associated with VEGF receptors. The VEGF-KDR/Flk-1 mediated signal is indispensable for the differentiation of ECs and blood cells in embryo. The VEGF-KDR/Flk-1 mediated signal also play an important role in adult, and stimulates protease synthesis in ECs and promotes EC migration and proliferation. VEGF-induced angiogenesis results beneficial effects in several animal models of myocardial or limb ischemia. Currently, several clinical trials are ongoing to test the hypothesis that VEGF-induced angiogenesis may be beneficial for these conditions.

著者

西平 順

出版者

一般社団法人 日本炎症・再生医学会

雑誌

炎症・再生 (ISSN:13468022)

巻号頁・発行日

vol.21, no.5, pp.531-539, 2001-09-28 (Released:2010-04-12)

参考文献数

46

---

Since the isolation of the cDNA of macrophage migration inhibitory factor (MIF), a number of novel biological properties of this cytokine have been discovered. The primary amino acid sequence of MIF is well conserved among a wide range of species. MIF is constitutively expressed not only in T cells, but also in a variety of other cells, including macrophages and epithelial cells of various organs. With regard to its biological function, MIF plays an important role as a proinflammatory cytokine, initiating production of other inflammatory cytokines, and as an anterior pituitary-derived hormone, potentiating lethal endotoxemia. In particular, it should be emphasized that this protein has the potential to override the glucocorticoid-mediated suppression of inflammatory and immune responses. Judging from an array ofin vivostudies, it is clear that anti-MIF antibodies efficiently suppress endotoxin-and exotoxin-induced inflammation and immune responses as well as tumor growth and angiogenesis. This review presents the latest findings on the roles of MIF in inflammatory and immune responses, as well as in cell growth and differentiation.

著者

川人 豊

出版者

一般社団法人 日本炎症・再生医学会

雑誌

炎症・再生 (ISSN:13468022)

巻号頁・発行日

vol.23, no.2, pp.74-83, 2003 (Released:2006-12-01)

参考文献数

51

被引用文献数

1

---

Peroxisome proliferator-activated receptors (PPARs), are members of the nuclear hormone receptors superfamily of ligand-activated transcriptional factors that include receptors for steroids, thyroid hormone, vitamin D3 and retinoic acid. PPAR binds to peroxisome proliferator responsive element (PPRE) as a heterodimer with the retinoic receptor (RXR) in the regulation of PPAR target genes. PPARs have been suggested to be important immunomodulatory factors as well as fatty acid regulators. PPARs modulate these activities in different immune cell types such as monocyte/macrophages, lymphocytes, and endothelial cells. PPAR-γ ligands lead to inhibition of the expression of nitric oxide, cytokines, chemokines and adhesion molecules, in part by antagonizing the activities of the transcription factors such as AP-1, and NF-κB. Moreover PPAR-γ ligands including antidiabetic thiazolidinedione and 15-deoxy-Δ12,14-prostaglandin J2 have potent tumor modulatory effects against several cancers. PPAR-γ also expressed in chondrocytes, synovial and bone tissues. Activation of the PPAR-γ induced RA synoviocyte apoptosis and suppression of osteoclast differentiatoin in vitro, and ameliorated adjuvant- induced arthritis with suppression of pannus formation and mononuclear cell infiltration in rats. These findings suggest that PPAR-γ ligands may potentially be useful for the treatment of chronic inflammatory diseases including arthritic joint diseases.

著者

中原 貴 中村 達雄 田畑 泰彦 江藤 一洋 清水 慶彦

出版者

日本炎症・再生医学会

雑誌

炎症・再生 : 日本炎症・再生医学会雑誌 = Inflammation and regeneration (ISSN:13468022)

巻号頁・発行日

vol.23, no.2, pp.116-121, 2003-03-10

参考文献数

26

被引用文献数

3 2

---

Our strategy for tissue regeneration is to induce maximum intrinsic healing potential at the site of a tissue defect, applying the elements of tissue engineering. Regeneration of periodontal tissues occurs through the combined application of a collagen sponge scaffold and gelatin microspheres incorporating basic fibroblast growth factor (bFGF) for controlled release. This &ldquo;sandwich membrane&rdquo; with or without bFGF (100&mu;g) was applied to a three-walled alveolar bone defect (3 x 4 x 4 mm) in nine dogs. Periodontal tissues, both hard and soft, treated with bFGF were effectively regenerated four weeks after the operation with functional recovery of the periodontal ligament in parts. Next, the effect of combining cells with the treatment was evaluated. Periodontal fenestration defects (6 x 4 mm) were created bilaterally in the maxillary canines of six dogs. One of these was filled with the collagen sponge scaffold seeded with autologous periodontal ligament-derived cells (3 x 10⁵), and the other was left empty. After four weeks, on the cell-seeded side, regeneration of the cementum was observed uniformly on the root surfaces, indicating that the seeded cells had formed new cementum. Our findings suggest a promising new approach to periodontal regeneration that is based upon <I>in situ</I> tissue engineering.

著者

湯本 健司 辻 邦和 二藤 彰 野田 政樹

出版者

日本炎症・再生医学会

雑誌

炎症・再生 (ISSN:13468022)

巻号頁・発行日

vol.23, no.4, pp.237-239, 2003 (Released:2006-12-01)

参考文献数

19

---

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.

著者

冨岡 玖夫

出版者

The Japanese Society of Inflammation and Regeneration

雑誌

炎症・再生 (ISSN:13468022)

巻号頁・発行日

vol.22, no.1, pp.7-8, 2002

著者

岡田 誠司 岩波 明生 石井 賢 中村 雅也 戸山 芳昭 岡野 栄之

出版者

日本炎症・再生医学会

雑誌

炎症・再生 (ISSN:13468022)

巻号頁・発行日

vol.24, no.6, pp.602-610, 2004 (Released:2006-10-25)

参考文献数

43

---

Neural stem cells (NSCs) are multipotential progeniotr cells, which can generate neurons, astrocytes, and oligodendrocytes, the three major cell types in the central nervous system. They also have the self-renewal activity and can be expanded in an undifferentiated state in vitro. Due to their capability of multipotency and chemotaxis for lesion site, there has been increasing interest in the identification and characterization of NSCs for therapeutic applications. However some numbers of recent studies demonstrated the existence of endogenous NSCs in adult mammalian central nerve system, their self-repairing activity is very faint. The cause of poor regenerative capability would be included microenvironmental factors that inhibit neurogenesis and axonal regeneration. We have investigated the effect of NSCs transplantation and modification the microenvironment for experimental spinal cord injury. This review will provide an overview of therapeutic strategy for neurodegenerative diseases and traumatic injury, such as Parkinson's disease and spinal cord injury.

著者

審良 静男

出版者

日本炎症・再生医学会

雑誌

炎症・再生 (ISSN:13468022)

巻号頁・発行日

vol.23, no.4, pp.211-217, 2003 (Released:2006-12-01)

参考文献数

26

被引用文献数

1 2

---

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.