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ABSTRACT: The ligand for CD137 (CD137L; also called 4-1BBL) is mainly expressed on activated APCs such as dendritic cells, B cells and macrophages. Even though CD137L functions as a trigger of the CD137 signaling pathway for T cell activation and expansion, engagement of CD137L can deliver a signal leading to the production of proinflammatory cytokines in macrophages.
We generated cell-permeable TAT-CD137L cytoplasmic domain fusion protein (TAT-CD137Lct) and examined its ability to initiate the CD137L reverse signaling pathway.
Treatment of TAT-CD137Lct induced the production of high levels of IL-6 and TNF-α mRNAs and proteins in peritoneal macrophages. TAT-CD137Lct increased phosphorylation of Erk, p38 MAPK and Jnk, and activated transcription factors C/EBP and CREB. However, TAT-CD137Lct did not visibly affect the degradation of the inhibitor of NF-kB (IkBα). We further demonstrated that JNK activation was required for TAT-CD137Lct-induced production of TNF-α, while activation of Erk and p38 MAPK were involved in IL-6 and TNF-α production.
Our results suggest that TAT-CD137Lct is an effective activator for the CD137L reverse signaling pathway.
Immune Network 08/2011; 11(4):216-22.
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Eun Jung Choi,
Dong Hee Kim,
Jae Geun Kim,
Dong Yeol Kim, Jung Dae Kim,
Ok Ju Seol,
Choon Soo Jeong,
Jeong Woo Park,
Min Young Choi,
Sung Goo Kang,
Maria E Costa,
Sergio R Ojeda,
Byung Ju Lee
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ABSTRACT: NELL2 (neural tissue-specific epidermal growth factor-like repeat domain-containing protein) is a secreted glycoprotein that is predominantly expressed in neural tissues. We reported previously that NELL2 mRNA abundance in brain is increased by estrogen (E2) treatment and that NELL2 is involved in the E2-dependent organization of a sexually dimorphic nucleus in the preoptic area. In this study we cloned the mouse NELL2 promoter and found it to contain two half-E2 response elements. Electrophoretic mobility shift assays and promoter assays showed that E2 and its receptors (ERalpha and ERbeta) stimulated NELL2 transcription by binding to the two half-E2 response elements. Hippocampal neuroprogenitor HiB5 cells expressing recombinant NELL2 showed increased cell survival under cell death-inducing conditions. Blockade of endogenous synthesis of NELL2 in HiB5 cells abolished the cell survival effect of E2 and resulted in a decrease in phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2). These data suggest that the NELL2 gene is trans-activated by E2 and contributes to mediating the survival promoting effects of E2 via intracellular signaling pathway of ERK.
Journal of Biological Chemistry 08/2010; 285(32):25074-84. · 4.77 Impact Factor
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Eun Jung Choi,
Dong Hee Kim,
Jae Geun Kim,
Dong Yeol Kim, Jung Dae Kim,
Ok Ju Seol,
Choon Soo Jeong,
Jeong Woo Park,
Min Young Choi,
Sung Goo Kang,
Maria E. Costa,
Sergio R. Ojeda,
Byung Ju Lee
[show abstract]
[hide abstract]
ABSTRACT: NELL2 (neural tissue-specific epidermal growth factor-like repeat domain-containing protein) is a secreted glycoprotein that
is predominantly expressed in neural tissues. We reported previously that NELL2 mRNA abundance in brain is increased by estrogen (E2) treatment and that NELL2 is involved in the E2-dependent organization
of a sexually dimorphic nucleus in the preoptic area. In this study we cloned the mouse NELL2 promoter and found it to contain two half-E2 response elements. Electrophoretic mobility shift assays and promoter assays
showed that E2 and its receptors (ERα and ERβ) stimulated NELL2 transcription by binding to the two half-E2 response elements. Hippocampal neuroprogenitor HiB5 cells expressing recombinant
NELL2 showed increased cell survival under cell death-inducing conditions. Blockade of endogenous synthesis of NELL2 in HiB5
cells abolished the cell survival effect of E2 and resulted in a decrease in phosphorylation of extracellular signal-regulated
kinase 1 and 2 (ERK1/2). These data suggest that the NELL2 gene is trans-activated by E2 and contributes to mediating the survival promoting effects of E2 via intracellular signaling
pathway of ERK.
Journal of Biological Chemistry 08/2010; 285(32):25074-25084. · 4.77 Impact Factor
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Sang-Chul Lee,
Seong-A Ju,
Boo-Hee Sung,
Sook-Kyoung Heo,
Hong Rae Cho,
Eun A Lee, Jung Dae Kim,
In Hee Lee,
Sang-Min Park,
Quang Tam Nguyen,
Jae-Hee Suh,
Byung-Sam Kim
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ABSTRACT: The tumor necrosis factor receptor family molecule 4-1BB (CD137) has diverse roles in adaptive and innate immune responses. However, little is known of its role in bacterial infections. Previously, we showed that 4-1BB-deficient mice have enhanced susceptibility to Listeria monocytogenes infection, and mice pretreated with agonistic anti-4-1BB antibody (3E1) were much more resistant to L. monocytogenes infection than mice treated with control antibody. In this study, we report that stimulating 4-1BB by administering 3E1 in the early phase of L. monocytogenes infection is critical for promoting the survival of mice by inducing rapid infiltration of neutrophils and monocytes into L. monocytogenes-infected livers. The levels of tumor necrosis factor alpha, interleukin 6, and monocyte chemoattractant protein 1 in the livers of 3E1-treated mice increased as early as 30 min postinfection and peaked by 1 to 2 h, while those in mice treated with control antibody started to increase only at 16 h postinfection. Monocytes and neutrophils from the 3E1-treated mice had higher levels of activation markers, phagocytic activity, and reactive oxygen species than those from control mice. In vitro stimulation of 4-1BB induced the production of the inflammatory cytokines/chemokines of neutrophils, but not those of monocytes. These results suggest that 4-1BB stimulation of neutrophils in the early phase of L. monocytogenes infection causes rapid production of inflammatory cytokines/chemokines and that the subsequent infiltration of neutrophils and monocytes is crucial for eliminating the infecting L. monocytogenes.
Infection and immunity 03/2009; 77(5):2168-76. · 4.21 Impact Factor
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ABSTRACT: To understand the effect of carbon doping on the superconductivity in MgB(2), we obtained the angle- and temperature-dependent upper critical fields [H(c2)(θ) and H(c2)(T)] for Mg(B(1-x)C(x))(2) single crystals (x = 0.06 and 0.1) from resistivity measurements while varying the temperature, the field, and the direction of the field. The detailed values of the diffusivity for two different directions for each σ-band and π-band were obtained to explain both the temperature- and the angle-dependent H(c2) by using the dirty-limit two-gap model. The induced impurity scattering of the σ-band and the π-band for both the ab-plane and the c-direction is studied.
Journal of Physics Condensed Matter 06/2007; 19(24):242201. · 2.55 Impact Factor
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ABSTRACT: We synthesized Ca1−xNaxCuO2Cl2 single crystals for 0.06⩽x⩽0.18 in the several GPa pressure range. The Na content, x, critically depended on the applied pressure, not the initial stoichiometric composition. A superconducting transition temperature of 27K was obtained for x∼0.18, which is the highest Tc reported so far for this compound.
Physica C-superconductivity and Its Applications - PHYSICA C. 01/2007; 460:78-79.
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ABSTRACT: We report magnetization measurements of grain-aligned Ba2Ca2Cu3O6(O,F)2 with Tc≃108 K. The interlayer distance of the material is the shortest among known tri-layer superconductors. Unexpectedly, the magnetization data show that the coupling strength between CuO2 layers is rather weak. A direct reflection of the weak coupling is highly suppressed irreversibility line, i.e. a broad reversible region in H–T plane. The decoupling field obtained from the irreversibility line is less than 0.1 T, which is comparable with that of quasi two-dimensional superconductor Bi2Sr2CaCu2O8+δ. Comparison of data with the Hao–Clem model gives characteristic parameters [ξab(0) and λab(0)] and the critical fields [Hc(0) and Hc2c(0)]. A large value of penetration depth, λab(0)=240 nm reflects a small carrier concentration in CuO2 planes, and explains the reason of the weak interlayer coupling.
Solid State Communications.
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ABSTRACT: The equilibrium magnetization of grain-aligned HgBa2Ca4Cu5O12+y (Hg1245) with Tc≃108 K was measured. The Ginzburg-Landau parameter (κ), obtained by using the Hao-Clem model, increased unphysically with increasing temperature for T∕Tc⩾0.7, which indicates that the fluctuation is greatly enhanced. The two-dimensional scaling behavior of the magnetization and the temperature variation of the irreversibility field Hirr(T) from a power-law behavior at low fields to an exponential behavior at high fields indicate that Hg1245 is highly anisotropic, which seems to be affected by the appearance of antiferromagnetism at the inner CuO2 planes while blocking the coupling of the superconductivity between the outer CuO2 layers.
Phys. Rev. B. 77(2).
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ABSTRACT: We report the reversible magnetization of the Ca2−xNaxCuO2Cl2 (x=0.18) single crystal for H‖c up to 1.2 T to study the effect of oxygen replacement by chlorine at the apical site. The superconducting transition temperature Tc (∼27 K) of this single crystal is the highest reported in this family. Various thermodynamic parameters, such as the penetration depth λab(0), the coherence length ξab(0), the critical field Hc(0), the upper critical field Hc2(0) and the Ginzburg-Landau parameter κ, are also reported. Compared to the iso-structural compound La1.82Sr0.18CuO4 with apical oxygen, Ca1.82Na0.18CuO2Cl2 has two significant differences: (1) λab(0) is larger, so the Cooper pair density is quite reduced, and (2) the anisotropic nature is more enhanced. From these observations, chlorine at the apical site is thought to be less effective than oxygen in supplying charge carriers to the CuO2 planes; as a result, the interlayer coupling between the CuO2 planes is weakened.
Phys. Rev. B. 72(22).
