Targeting TNF-α suppresses the production of MMP-9 in human salivary gland cells

Objective: Tumor necrosis factor-α (TNF-α) is a pleiotropic cytokine that plays an essential role in inflammation and apoptosis. Our previous study suggested that TNF-α-induced activation of matrix metalloproteinase-9 (MMP-9) resulted in the destruction of acinar tissue in the salivary glands of patients with Sjögren’s syndrome (SS) via disruption of the acinar cell-basement membrane. Recently, a wide array of biological agents has been designed to inhibit TNF, including etanercept and adalimumab. In this study, we demonstrate the suppressive effect of anti-TNF agents on TNF-α-induced MMP-9 production in NS-AV-AC, an immortalized human salivary gland acinar cell line. Materials and Methods: NS-AV-AC cells were treated with etanercept or adalimumab after TNF-α treatment. MMP-9 production and enzymatic activity were, respectively, visualized by real-time PCR and ELISA assay, and evaluated by gelatin zymography, and apoptosis was evaluated by DNA fragmentation assay. Results: TNF-α induced the production of MMP-9 in NS-SV-AC cells. However, this production was greatly inhibited by treatment with etanercept or adalimumab. In addition, TNF-α-induced DNA fragmentation was prevented by treatment with etanercept or adalimumab. Conclusions: These results may indicate that anti-TNF agents would have therapeutic efficacy for preventing destruction of the acinar structure in the salivary glands of patients with SS

Catalyst Development of Microbial Fuel Cells for Renewable-Energy Production

In this chapter, we focus on microbial fuel cells (MFCs) that convert the energy from organic matters into electrical energy using microorganisms. MFCs are greatly expected to be used as a relatively low-cost and safe device for generating renewable energy using waste biomass as a raw material. At present, however, it has not reached the desired practical application because of the low-power generation; hence, improvements on fuel cell efficiency, such as electrode materials, are still being examined. Here, we focus on the microorganisms that can be used as catalysts and play a central role in improving the efficiency of the fuel cells. Several kinds of microbial catalysts are used in MFCs. For example, Shewanella oneidensis has been well studied, and as known, since S. oneidensis transports the electrons generated within the cell to the surface layer, it does not require a mediator to pass the electrons from the cells to the electrode. Furthermore, Escherichia coli and Saccharomyces cerevisiae, a model organism for MFCs, are also used. The improvements of such microbial catalysts have also been proceeding actively. Here, we elaborated on the principle of MFCs as well as the current situation and latest research on the catalyst development

Sedimentary environments of mangrove swamp in the Funaura Bay, Iriomote Island, Okinawa Prefecture, Southwest Japan

The distribution of conch shell contained in clastic sediments in the mangrove swamps in the Funaura Bay, Iriomote Island, Okinawa Prefecture was studied. The sediments in the mangrove swamp are mainly composed of up to 90% sands. The sand clasts are inferred to be derived from the sandstone of Miocene Yaeyama Group. The conch shells are richer in the muddy fraction than the sandy fraction. Many Terebralia palustris inhabit the mangrove swamp. However few dead shells were also observed in the sediments. Effect of selective transportation hermit crabs is considered to be the cause of this distribution

シェーグレン ショウコウグン ニ タイスル ビョウキ タイオウガタ テーラーメード イリョウ ノ コウチク

Sjögren's syndrome (SS) is one of the most common rheumatic diseases. Histopathologic features of SS salivary glands include: (a) the eventual total replacement of the acinar structure by marked lymphocytic infiltrate and (b) the occurrence of various changes in the ductal structure within infiltrated areas, such as metaplasia, hyperplasia, thinning of ductal layer, or oncocytic change, and in some cases the formation of epimyoepithelial islands arising from ductal proliferation. Accordingly, surviving and/or proliferating ductal cells in SS salivary glands may be regarded as one of the possible sources for the improvement of salivary secretion. Thus far, I found that inhibition of TNF-α-induced MMP-9 production in acinar cells lead to restored integrity of the acinar structure in SS salivary glands. Therefore, in this review I would like to postulate a tailor-made therapy based on the diseasestage of SS. First, therapy for the inhibition of lymphocytic infiltrate into salivary glands by regulating balance of sex hormones in acinar cells (early stage of SS); second, therapy for the maintenance of stable acinar structure by inhibiting cytokine-induced basement membrane-degrading enzymes, such as MMP-9 (intermediate stage of SS); and third, therapy for the bestowal of ability to secrete saliva on ductal cells (late stage of SS). Hopefully, these disease stage-specific therapies would contribute to the improvement of QOL of SS patients

Role of CXCL10 in pathogenesis of Sjögren's syndrome

Sjögren's syndrome (SS) is a common autoimmune disease characterized by the destruction of acinar structure by marked lymphocytic infiltrates in the salivary and lacrimal glands, resulting in sicca symptoms. Gene expression profiling of lip salivary glands (LSGs) shows that C-X-C motif chemokine 10 (CXCL10) expression is upregulated in patients with primary SS (pSS). CXCL10 and its receptor, C-X-C receptor 3 (CXCR3), contribute to the pathogenesis of SS. We investigated the clinical significance of CXCL10 and CXCR3 in the autoimmune lesions of pSS and the molecular mechanisms of CXCL10 upregulation in the salivary gland cells. CXCL10 showed particularly intense staining in LSG ductal cells from pSS patients. CXCR3 expression was detected primarily in CD163+ macrophages. The number of CXCR3+CD163+ macrophages was inversely correlated with the severity of LSG inflammatory lesions. Our in vitro experiments demonstrated that human salivary gland ductal (NS-SV-DC) cells produced higher levels of CXCL10 than acinar (NS-SV-AC) cells. Furthermore, NS-SV-DC and NS-SV-AC cells had different regulators of CXCL10 enhancement: interferon (IFN)-γ had more potential than IFN-α, tumor necrosis factor (TNF)-α, and interleukin (IL)1-β in the induction of CXCL10 production in NS-SV-DC cells, whereas TNF-α had the potential to induce CXCL10 production in NS-SV-AC cells. Our results suggest that CXCL10 overexpression in salivary glands is mainly caused by IFN-γ-stimulated salivary gland ductal cells. The enhanced production of CXCL10 by ductal cell IFN-γ results in the migration of CXCR3+ immune cells. CXCL10 plays an important role in SS pathogenesis, and CXCL10 regulation may be useful in the treatment of SS patients

ビスコクラウリン型アルカロイドであるセファランチンは、1次性シェーグレン症候群患者の唾液分泌量を著明に増加させる

Objective: Our previous findings suggested that the suppression of tumor necrosis factoralpha (TNF-α)-induced matrix metalloproteinase (MMP)-9 production by the biscoclaurine alkaloid cepharanthine could prevent the destruction of the acinar structure in the salivary glands of murine Sjögren's syndrome. Here, we examined the effect of cepharanthine on the salivary secretion in primary Sjögren's syndrome (pSS) patients. Methods: In this single-center, open-label pilot study, 29 patients with pSS (28 women, 1 man) received 6 mg/day orally cepharanthine for 12 months. Standard clinical assessments and stimulated salivary flow were examined at baseline and each month for 12 months in all 29 patients. In eight of the patients, inflammatory lesions in the salivary glands were histologically investigated before and after the cepharanthine treatment. We analyzed the expressions of p65, phosphorylated IκB-α, MMP-9, and type IV collagen immunohistochemically. Results: All patients completed the study without any adverse events. A significant increase in salivary flow was observed after the cepharanthine treatment compared to baseline. The serological analysis revealed that the 14 patients with an anti-Sjögren's-syndrome-related antigen A (anti-SSA/Ro) antibody value that was either negative or 64 U/ml did not. The immunohistochemical analysis demonstrated that although p65, phosphorylated IκB-α, and MMP-9 were more strongly stained in the acinar cells of the patients at baseline compared to the staining at the completion of cepharanthine treatment, the continuity of type IV collagen was observed following the cepharanthine treatment. These results indicate that cepharanthine could inhibit the phosphorylation of IκB-α, followed by the prevention of MMP-9 activation and the stabilization of type IV collagen. Conclusions: Our findings suggest that cepharanthine could be a promising agent for improving salivary secretion in pSS patients

ゼッツウ オ ウッタエル カンジャ ニツイテ カンガエル : ゼッツウショウ オ チュウシン ニ

Many patients with tongue pain are frequently found in clinics of oral medicine and surgery. There is a possibility that they include various diseases such as glossitis, tongue tumor, tongue trauma, anemia, neuralgia, oral infection, xerostomia, temporomandibular disorder, galvanism, irritant substance and glossodynia. We conducted a survey on the clinical status of 58 patients with tongue pain, and found that they consisted of 30 cases of oral candidiasis, 17 cases of oral xerostomia, 16 cases of glossodynia, 13 cases of glossitis and so on in order of prevalence. Further survey on these patients with oral candidiasis and xerostomia revealed that a large number of patients suffering from oral candidiasis had no clinical appearance in their tongues, and those of xerostomia didn't complain of thirst. Thus, because all these patients without any symptoms except for tongue pain might be diagnosed and treated as glossodynia, thorough examination such as cultivation and salivation tests should be performed in these patients. Next, we employed a novel approach to diagnose glossodynia based on heart rate variability. We examined whether or not heart rate variability reflects curative effects of linear polarized near-infrared light irradiation near stellate ganglion. The result showed that a time-dependent change of autonomic activity correlated with that of VAS value. These findings suggest that heart rate variability is useful for monitoring curative effects and estimation of prognosis

An Overview of Oral Pain : Orofacial Pain and Concomitant Symptoms

口の痛みには歯原性歯痛・非歯原性歯痛などがある。前者は歯を原因とする歯痛であり，従来の歯科治療（つまり歯を削る・抜くなど）によって対応可能で，これまで問題視されることはなかった。後者は歯を原因としない歯痛であり，従来の歯科治療は奏効し難く，対応に苦慮することが多い。これに鑑み，米国において新しい疾患概念「口腔顔面痛」が提唱され，本邦においても，その対策は喫緊の課題とされる。また，口腔顔面痛は随伴症状を有することも多い。その原因や症状は歯科領域に止まらず，内科・外科・精神神経科領域など多岐にわたり，的確な判断と対応が求められる。Oral pain may be due to odontogenic toothache, non-odontogenic toothache, or other causes. Odontogenic toothaches can be resolved by conventional dental treatments, but non-odontogenic toothaches are refractory to such treatments; dental practitioners have not yet devised a way to deal with them. In light of these circumstances, a new disease concept, orofacial pain（OFP）, was advocated in the United States. OFP is an urgent issue to be resolved in Japan, too. Individuals with OFP frequently present with concomitant symptoms, and these causes and symptoms of OFP are associated not only with dentistry but also fields of study such as medicine, surgery, and psychology. Appropriate clinical judgements and actions are required to deal with cases of OFP