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Yasuo Ota

Publications and source records attributed to Yasuo Ota.

7 recordsLinked to original sources
PubMed2003

Involvement of IRAK-M in peptidoglycan-induced tolerance in macrophages.

The molecular mechanisms by which pathogen-associated molecular patterns recognized by TLR2, such as peptidoglycan (PGN), induce homotolerance are largely unknown. It was recently reported that IRAK-M negatively regulates TLR signaling. In this study, we elucidate the molecular mechanisms of tolerance induced by PGN, with a focus on the role of IRAK-M. We demonstrate that pretreatment of macrophage RAW264.7 cells with a high concentration (30 microg/ml) of PGN for 16 h effectively induces tolerance against following stimulation with 30 microg/ml of PGN; while pretreatment with a low concentration (1 microg/ml) of PGN does not. IRAK-M is induced in cells treated with the high concentration of PGN 4-24 h after PGN stimulation, but not in cells treated with the low concentration of PGN up to 24 h after stimulation. Phosphorylation of MAPKs and IkappaBalpha is inhibited after the second PGN stimulation in tolerant cells. Kinase activity of IRAK-1 and association between IRAK-1 and MyD88 are also suppressed in PGN-induced tolerant cells. Furthermore, down-regulation of IRAK-M expression by small interfering RNAs specific for IRAK-M reinstates the production of TNF-alpha after PGN restimulation. These results suggest that induction of IRAK-M and inhibition of kinase activity of IRAK-1 are crucial to PGN-induced tolerance in macrophages.

Animals↗
PubMed2003

Expression and function of Toll-like receptors in eosinophils: activation by Toll-like receptor 7 ligand.

We investigated the expression of a panel of Toll-like receptors (TLRs) and their functions in human eosinophils. Eosinophils constitutively expressed TLR1, TLR4, TLR7, TLR9, and TLR10 mRNAs (TLR4 greater than TLR1, TLR7, TLR9, and TLR10 greater than TLR6). In contrast, neutrophils expressed a larger variety of TLR mRNAs (TLR1, TLR2, TLR4, TLR6, TLR8 greater than TLR5, TLR9, and TLR10 greater than TLR7). Although the expression levels in eosinophils were generally less prominent compared with those in neutrophils, eosinophils expressed a higher level of TLR7. Furthermore, among various TLR ligands (S-(2,3-bis(palmitoyloxy)-(2-RS)-propyl)-N-palmitoyl-Cys-Ser-(Lys)(4), poly(I:C), LPS, R-848, and CpG DNA), only R-848, a ligand of TLR7 and TLR8, regulated adhesion molecule (CD11b and L-selectin) expression, prolonged survival, and induced superoxide generation in eosinophils. Stimulation of eosinophils by R-848 led to p38 mitogen-activated protein kinase activation, and SB203580, a p38 mitogen-activated protein kinase inhibitor, almost completely attenuated R-848-induced superoxide generation. Although TLR8 mRNA expression was hardly detectable in freshly isolated eosinophils, mRNA expression of TLR8 as well as TLR7 was exclusively up-regulated by IFN-gamma but not by either IL-4 or IL-5. The up-regulation of the TLRs by IFN-gamma had potentially functional significance: the extent of R-848-induced modulation of adhesion molecule expression was significantly greater in cells treated with IFN-gamma compared with untreated cells. Although the natural ligands for TLR7 and TLR8 have not yet been identified, our results suggest that eosinophil TLR7/8 systems represent a potentially important mechanism of a host-defensive role against viral infection and mechanism linking exacerbation of allergic inflammation and viral infection.

Cell Adhesion Molecules↗
PubMed2003

Raf1 plays a pivotal role in lipopolysaccharide-induced activation of dendritic cells.

Activation of extracellular-regulated kinases 1/2 (ERK) is involved in lipopolysaccharide (LPS)-induced cellular responses such as the increased production of proinflammatory cytokines. However, mitogen-activated protein kinases (MAPKs) such as p38 are also activated by LPS and have been postulated to be important in the control of these end points. Therefore, establishing the relative contribution of MAPKs in each cell type is important, as is elucidating the molecular mechanisms by which these MAPKs are activated in LPS-induced signaling cascades. We demonstrated in DC2.4 dendritic cells that ERK regulates tyrosine phosphorylation of phosphatidyl-inositol-3-kinase (PI3-K) and the production of TNF-alpha. We also demonstrated that Raf1 is phosphorylated and involved in the production of TNF-alpha and tyrosine phosphorylation of PI3-K via ERK. Raf1 also regulates the activation of NF-kappaB. We propose that Raf1 plays a pivotal role in LPS-induced activation of the dendritic cells.

Animals↗
PubMed2003

Janus kinase 2 is involved in lipopolysaccharide-induced activation of macrophages.

The mechanisms by which lipopolysaccharide (LPS) is recognized, and how such recognition leads to innate immune responses, are poorly understood. Stimulation with LPS induces the activation of a variety of proteins, including mitogen-activated protein kinases (MAPKs) and NF-kappaB. Activation of protein tyrosine kinases (PTKs) is also necessary for a number of biological responses to LPS. We used a murine macrophage-like cell line, RAW264.7, to demonstrate that Janus kinase (JAK)2 is tyrosine phosphorylated immediately after LPS stimulation. Anti-Toll-like receptor (TLR)4 neutralization antibody inhibits the phosphorylation of JAK2 and the c-Jun NH2-terminal protein kinase (JNK). Both the JAK inhibitor AG490 and the kinase-deficient JAK2 protein reduce the phosphorylation of JNK and phosphatidylinositol 3-kinase (PI3K) via LPS stimulation. Pharmacological inhibition of the kinase activity of PI3K with LY-294002 decreases the phosphorylation of JNK. Finally, we show that JAK2 is involved in the production of IL-1beta and IL-6. PI3K and JNK are also important for the production of IL-1beta. These results suggest that LPS induces tyrosine phosphorylation of JAK2 via TLR4 and that JAK2 regulates phosphorylation of JNK mainly through activation of PI3K. Phosphorylation of JAK2 via LPS stimulation is important for the production of IL-1beta via the PI3K/JNK cascade. Thus JAK2 plays a pivotal role in LPS-induced signaling in macrophages.

Animals↗
PubMed2003

A patient with E. coli-induced pyelonephritis and sepsis who transiently exhibited symptoms associated with primary biliary cirrhosis.

A 28-year-old woman had chief complaints of headache and a 40 degrees C fever. At this time, findings indicative of inflammation including elevated CRP and increased WBC were observed, and E. coli was detected on blood and urine culture. As a result, the patient was diagnosed with pyelonephritis and sepsis. Furthermore, markedly increased hepatobiliary enzymes and elevated anti-mitochondrial antibody were confirmed. The administration of antimicrobial agents resulted in improvement of the pyelonephritis and sepsis and normalization of hepatobiliary enzyme and anti-mitochondrial antibody levels. It has been documented that the incidence of urinary tract infection is high among patients with primary biliary cirrhosis (PBC). The findings obtained from the present patient are of considerable interest in elucidating the mechanism of onset in PBC.

Adult↗
PubMed2003

Acute hepatitis E with elevated creatine phosphokinase.

Acute hepatitis E is caused by infection with hepatitis E virus, which is endemic in developing countries. Recently, the number of cases with acute hepatitis E is increasing in Japan due to increased travel to the endemic areas. This paper reports a case of a Japanese man with acute hepatitis E who had a history of traveling to south China. Serum creatine phosphokinase was elevated on admission without symptoms of muscle damage (isoenzyme MM 100%), and normalized in parallel with resolution of hepatitis, raising the possibility of an association between elevation of creatine phosphokinase and acute hepatitis E. However, we need to investigate further the incidence of elevation of serum creatine phosphokinase in many cases with acute viral hepatitis including hepatitis A, B, and C to determine whether muscle disorder is characteristic of acute hepatitis E.

Creatine Kinase↗