Molecular characterization of the β chain of the murine interleukin 5 receptor

Interleukin 5 (IL-5) is a multifunctional cytokine that regulates the proliferation and differentiation of hematopoietlc cells Including B cells and eosinophlls. The murine IL-5 acts on target cells via an IL-5 specific high-affinity receptor (Kd ≃ 150 pM) that has been proposed to be composed of at least two membrane polypeptide chains. The p60 component recognized by anti-murine IL-5 receptor mAbs H7 and T21 binds IL-5 with low affinity (Kd ≃ 10 nM). The other component is p130, detectable by following cross-linking experiments with IL-5. Using H7, T21, and R52.120 mAbs specific to murine IL-5 receptor, we characterized the molecular nature of the p130 of the high affinity receptor for murine IL-5. R52.120 mAb did not recognize the IL-5 binding recombinant p60 expressed on COS7 cells, but reacted with p130/140 on IL-5-dependent cell lines. R52.120 mAb showed partial inhibition of the IL-5-induced proliferation of the IL-5-dependent early B cell line Y16 at high IL-5 concentrations. Addition of R52.120 mAb together with H7 or T21 mAb caused more striking inhibition of the IL-5-dependent proliferation than that caused by either of them alone. R52.120 mAb down-regulated the number and dissociation constant of IL-5 binding sites with high affinity without affecting the levels of these with low-affinity. It also preferentially inhibited the formation of the cross-linked complex of p130 with radlolabeledIL-5. These results Indicate that p130/p140, recognized by R52.120 mAb, Is indispensable, together with p60, for the formation of high affinity IL-5 receptor. We propose to designate p60 and p130/p140 as the α and β chain of IL-5 receptor, respectivel

Partial suppression of M1 microglia by Janus kinase 2 inhibitor does not protect against neurodegeneration in animal models of amyotrophic lateral sclerosis

BACKGROUND: Accumulating evidence has shown that the inflammatory process participates in the pathogenesis of amyotrophic lateral sclerosis (ALS), suggesting a therapeutic potential of anti-inflammatory agents. Janus kinase 2 (JAK2), one of the key molecules in inflammation, transduces signals downstream of various inflammatory cytokines, and some Janus kinase inhibitors have already been clinically applied to the treatment of inflammatory diseases. However, the efficacy of JAK2 inhibitors in treatment of ALS remains to be demonstrated. In this study, we examined the role of JAK2 in ALS by administering a selective JAK2 inhibitor, R723, to an animal model of ALS (mSOD1(G93A) mice). FINDINGS: Orally administered R723 had sufficient access to spinal cord tissue of mSOD1(G93A) mice and significantly reduced the number of Ly6c positive blood monocytes, as well as the expression levels of IFN-γ and nitric oxide synthase 2, inducible (iNOS) in the spinal cord tissue. R723 treatment did not alter the expression levels of Il-1β, Il-6, TNF, and NADPH oxidase 2 (NOX2), and suppressed the expression of Retnla, which is one of the markers of neuroprotective M2 microglia. As a result, R723 did not alter disease progression or survival of mSOD1(G93A) mice. CONCLUSIONS: JAK2 inhibitor was not effective against ALS symptoms in mSOD1(G93A) mice, irrespective of suppression in several inflammatory molecules. Simultaneous suppression of anti-inflammatory microglia with a failure to inhibit critical other inflammatory molecules might explain this result. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-014-0179-2) contains supplementary material, which is available to authorized users

Effects of Disinfection on Alginate Impression Materials with Sanitating and Fixing Agent for Alginate Impression Materials (ALGIGUARDR)

本論文の要旨は,平成7年9月の第34回広島県歯科医学会において発表した

Tracheal cartilage regeneration by slow release of basic fibroblast growth factor from a gelatin sponge

ObjectiveWe investigated whether implantation of a gelatin sponge, releasing basic fibroblast growth factor slowly (b-FGF) into a tracheal cartilage defect, would induce regeneration of autologous tracheal cartilage.MethodsWe created a 1-cm defect in the midventral portion of each of 10 consecutive cervical tracheal cartilage rings in 12 experimental dogs. In the control group (n = 4), the resulting defects were left untreated. In the gelatin group (n = 4), empty gelatin sponges were implanted in the defects. In the basic fibroblast growth factor group (n = 4), gelatin sponges incorporating 100 μg of b-FGF solution were implanted in the defects. We killed the 4 dogs in each group at 1, 3, 6, and 12 months after implantation, respectively, and examined the implant sites macro- and microscopically.ResultsIn the control and gelatin groups, no regenerated cartilage was observed in the tracheal cartilage defects, and the width of the gap between the host cartilage stumps had shrunk. In the b-FGF group, regenerated cartilage was observed in all dogs. The proportion of the defect in the host cartilage occupied by regenerated cartilage was 13%, 84%, 75%, and 69% at 1, 3, 6, and 12 months, respectively. The regenerated cartilage was fibrous cartilage covered with perichondrium, which grew from the host perichondrium and showed continuity with the host cartilage stumps.ConclusionsImplantation of a gelatin sponge slowly releasing basic fibroblast growth factor induces tracheal cartilage regeneration, which subsequently fills a large proportion of experimentally created tracheal cartilage defects within 12 months after implantation