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Takehiko Yanagihara - One of the best experts on this subject based on the ideXlab platform.
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il 6 plays a crucial role in the Induction Phase of myelin oligodendrocyte glycoprotein 35 55 induced experimental autoimmune encephalomyelitis
Journal of Neuroimmunology, 1999Co-Authors: Yoshinobu Okuda, Saburo Sakoda, Harutoshi Fujimura, Yukihiko Saeki, T Kishimoto, Takehiko YanagiharaAbstract:Abstract We investigated the role of IL-6 in myelin oligodendrocyte glycoprotein (MOG) peptide induced experimental autoimmune encephalomyelitis (EAE) using IL-6-deficient mice and found that IL-6-deficient mice were resistant to active Induction of EAE, but that the treatment of those mice with IL-6 during the preclinical Phase caused typical EAE. We also found that both wild-type and IL-6-deficient mice were resistant to passive transfer of EAE by lymphocytes from IL-6-deficient mice, but that passive transfer of lymphocytes from wild-type mice induced typical EAE in IL-6-deficient mice. Histological abnormalities of the central nervous system (CNS) in those IL-6-deficient mice with EAE were similar to those in wild-type mice with EAE. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed no difference in the production of inflammatory cytokines such as IL-1β, IL-2, TNF-α, and IFN-γ in the CNS of IL-6-deficient mice with EAE as compared to the CNS of wild-type mice with EAE. These results indicated that IL-6 might be an important factor in the Induction Phase, but might have little influence on the effector Phase of EAE. We further estimated the production of cytokines in MOG-stimulated lymph node (LN) cells by enzyme-linked immunosorbent assay. Increased IL-4 and IL-10 production and reduced IL-2 and IFN-γ production were observed in LN cells from IL-6-deficient mice as compared to LN cells from wild-type mice. These results suggested that a shift of T cell responses from Th1 to Th2 might explain the resistance of IL-6-deficient mice to EAE. Taken together, IL-6 may play a crucial role in the Induction Phase of EAE by modulating Th1/Th2 balance.
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il 6 plays a crucial role in the Induction Phase of myelin oligodendrocyte glycoprotein 35 55 induced experimental autoimmune encephalomyelitis
Journal of Neuroimmunology, 1999Co-Authors: Yoshinobu Okuda, Saburo Sakoda, Harutoshi Fujimura, Yukihiko Saeki, T Kishimoto, Takehiko YanagiharaAbstract:We investigated the role of IL-6 in myelin oligodendrocyte glycoprotein (MOG) peptide induced experimental autoimmune encephalomyelitis (EAE) using IL-6-deficient mice and found that IL-6-deficient mice were resistant to active Induction of EAE, but that the treatment of those mice with IL-6 during the preclinical Phase caused typical EAE. We also found that both wild-type and IL-6-deficient mice were resistant to passive transfer of EAE by lymphocytes from IL-6-deficient mice, but that passive transfer of lymphocytes from wild-type mice induced typical EAE in IL-6-deficient mice. Histological abnormalities of the central nervous system (CNS) in those IL-6-deficient mice with EAE were similar to those in wild-type mice with EAE. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed no difference in the production of inflammatory cytokines such as IL-1beta, IL-2, TNF-alpha, and IFN-gamma in the CNS of IL-6-deficient mice with EAE as compared to the CNS of wild-type mice with EAE. These results indicated that IL-6 might be an important factor in the Induction Phase, but might have little influence on the effector Phase of EAE. We further estimated the production of cytokines in MOG-stimulated lymph node (LN) cells by enzyme-linked immunosorbent assay. Increased IL-4 and IL-10 production and reduced IL-2 and IFN-gamma production were observed in LN cells from IL-6-deficient mice as compared to LN cells from wild-type mice. These results suggested that a shift of T cell responses from Thl to Th2 might explain the resistance of IL-6-deficient mice to EAE. Taken together, IL-6 may play a crucial role in the Induction Phase of EAE by modulating Th1/Th2 balance.
Hisayuki Ueno - One of the best experts on this subject based on the ideXlab platform.
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b7 h3 regulates the development of experimental allergic conjunctivitis in mice
Immunology Letters, 2007Co-Authors: Atsuki Fukushima, Tamaki Sumi, Ken Fukuda, Naoki Kumagai, Teruo Nishida, Tomohide Yamazaki, Hisaya Akiba, Ko Okumura, Hideo Yagita, Hisayuki UenoAbstract:B7-H3 negatively regulates Th1-mediated immune responses. Here, we aimed to investigate whether B7-H3 is involved in the development of murine experimental allergic conjunctivitis (EC), which is predominantly mediated by Th2 cells. Intraperitoneal injection of anti-B7-H3 Ab during the Induction Phase of EC significantly augmented the severity of EC evaluated as conjunctival eosinophil numbers and Ag-induced IL-5 production by splenocytes. Injection of anti-B7-H3 Ab during the effector Phase of EC did not significantly affect the severity of EC. In addition, transfer of Ag-primed splenocytes treated with anti-B7-H3 Ab in vitro did not significantly affect the severity of EC, compared to the splenocytes treated with the control Ab. Thus, regulation of EC by blocking of B7-H3 was observed during the Induction Phase but not the effector Phase. Moreover, this study provides a new notion that B7-H3 regulates not only Th1-mediated but also Th2-mediated immune reactions.
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antibodies to t cell ig and mucin domain containing proteins tim 1 and 3 suppress the Induction and progression of murine allergic conjunctivitis
Biochemical and Biophysical Research Communications, 2007Co-Authors: Atsuki Fukushima, Tamaki Sumi, Ken Fukuda, Naoki Kumagai, Teruo Nishida, Hisaya Akiba, Ko Okumura, Hideo Yagita, Hisayuki UenoAbstract:Abstract The T cell Ig and mucin domain-containing proteins (Tim) regulate Th1- and Th2-mediated immune responses. We investigated the ability of Abs blocking Tim-1 or Tim-3 ligand-binding activity to prevent and treat murine experimental allergic conjunctivitis (EC), a Th2-mediated disease. Treatment with either Ab during the Induction Phase of EC in actively immunized wild-type mice suppressed EC and upregulated Th1 and Th2 immune responses. In contrast, both Abs exacerbated EC in actively immunized IFN-γ-knockout mice. Thus, both anti-Tim Abs suppress the pathogenic immune responses generated in the Induction Phase by upregulating systemic IFN-γ production. Treatment of actively immunized mice and passively immunized mice with either anti-Tim Ab just prior to RW challenge also suppressed EC. Thus, treatment with anti-Tim-1 or anti-Tim-3 Ab can suppress both the Induction and progression of EC, which could indicate potential preventive and/or therapeutic approaches for allergic diseases such as allergic conjunctivitis.
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involvement of programmed death ligand 2 pd l2 in the development of experimental allergic conjunctivitis in mice
British Journal of Ophthalmology, 2006Co-Authors: Atsuki Fukushima, Hideo Yagita, Tomoko Yamaguchi, Miyuki Azuma, Hisayuki UenoAbstract:Background/aim: Involvement of programmed death-1 (PD-1) and its ligands has been demonstrated in experimental allergic airway disease. Here, the authors aimed to examine whether PD-1 and its ligands are involved in the development of experimental allergic conjunctivitis (EC) in mice. Methods: EC was induced in Balb/c mice by active immunisation with short ragweed pollen (RW) in alum. 10 days later (day 10), the mice were challenged with eye drops containing RW. 24 hours after the challenge, conjunctivas, spleens, and sera were harvested for histological analysis, cytokine assays, and measurement of RW specific Ig levels. The actively immunised mice were treated with anti-PD-1, anti-PD-L1, anti-PD-L2 antibodies (Abs), or normal rat immunoglobulin G (nrIgG) during either the Induction (day 0, 2, 4, 6, and 8) or the effector (2 hours before RW challenge on day 10) Phase. Results: Ab treatment during the Induction Phase did not affect eosinophil infiltration although immune responses were modulated. In contrast, treatment with anti-PD-L2 Ab, but not anti-PD-1 or anti-PD-L1 Ab, during the effector Phase significantly increased eosinophil infiltration into the conjunctiva without affecting systemic immune responses. Conclusions: Similar to allergic airway inflammation, PD-L2 is involved in the development of EC during the effector Phase but not the Induction Phase.
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exertion of the suppressive effects of ifn γ on experimental immune mediated blepharoconjunctivitis in brown norway rats during the Induction Phase but not the effector Phase
British Journal of Ophthalmology, 2002Co-Authors: Atsuki Fukushima, Kazuyo Fukata, Akemi Ozaki, Masaru Takata, N Kuroda, Hideaki Enzan, Hisayuki UenoAbstract:Background/aims: Interferon gamma (IFN-γ) knockout mice exhibit severe allergic conjunctivitis (AC), indicating that IFN-γ regulates the development of AC. The authors examined whether this inhibitory effect of IFN-γ is exerted during the Induction or effector Phase of experimental AC. Methods: Experimental immune mediated blepharoconjunctivitis (EC) was induced in Brown Norway (BN) rats, using ovalbumin (OVA) as the antigen. To investigate the role of IFN-γ in the Induction Phase, EC was induced by active immunisation and IFN-γ (10 μg/time, total 70 μg), or phosphate buffered saline (PBS) as a control, was injected intraperitoneally every other day from the day of immunisation. The rats were challenged with OVA eye drops 13 days after immunisation, and 24 hours later, the eyes were harvested for histology. To examine the effects of IFN-γ in the effector Phase, OVA specific T cells were transferred into syngeneic rats and IFN-γ (10 μg/time, total 50 μg) or PBS was injected each day after the transfer until Induction of EC 4 days later with an OVA challenge. To investigate the role of endogenous IFN-γ during the effector Phase, an anti-IFN-γ monoclonal antibody (3 mg/time) was injected on days 3 and 4. Results: Injection of IFN-γ into actively immunised rats suppressed eosinophilic infiltration but not infiltration of mononuclear cells. In contrast, neither IFN-γ nor anti-IFN-γ affected EC in passively immunised rats. Conclusion: IFN-γ is a suppressive cytokine for the development of EC and exerts this suppressive effect during the Induction Phase.
Irene Salinas - One of the best experts on this subject based on the ideXlab platform.
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effects of experimental terrestrialization on the skin mucus proteome of african lungfish protopterus dolloi
Frontiers in Immunology, 2018Co-Authors: Ryan D Heimroth, Elisa Casadei, Irene SalinasAbstract:Animal mucosal barriers constantly interact with the external environment and this interaction is markedly different in aquatic and terrestrial environments. Transitioning from water to land was a critical step in vertebrate evolution but the immune adaptations that mucosal barriers such as the skin underwent during that process are essentially unknown. Vertebrate animals such as the African lungfish have a bimodal life, switching from freshwater to terrestrial habitats when environmental conditions are not favorable. African lungfish skin mucus secretions contribute to the terrestrialization process by forming a cocoon that surrounds and protect the lungfish body. The goal of this study is to characterize the skin mucus immunoproteome of African lungfish, Protopterus dolloi, before and during the Induction Phase of terrestrialization as well as the immunoproteome of the gill mucus during the terrestrialization Induction Phase. Using LC-MS/MS, we identified a total of 974 proteins using a lungfish Illumina RNA-seq database, 1256 proteins from previously published lungfish Sequence Read Archive (SRA) and 880 proteins using a lungfish 454 RNA-seq database for annotation in the three samples analyzed (free-swimming skin mucus, terrestrialized skin mucus and terrestrialized gill mucus). The terrestrialized skin mucus proteome was enriched in proteins with known antimicrobial functions such as histones and S100 proteins compared to free-swimming skin mucus. In support, gene ontology analyses showed that the terrestrialized skin mucus proteome has predicted functions in processes such as viral process, defense response to Gram negative bacterium and tumor necrosis factor mediated signaling. Importantly, we observed a switch in immunoglobulin heavy chain secretion upon terrestrialization, with IgW1L and IgM1 present in free-swimming skin mucus and IgW1L, IgM1 and IgM2 in terrestrialized skin mucus. Combined, these results indicate an increase investment in the production of unique immune molecules in P. dolloi skin mucus in response to terrestrialization that likely better protect lungfish against external aggressors found in land.
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Table_5_Effects of Experimental Terrestrialization on the Skin Mucus Proteome of African Lungfish (Protopterus dolloi).XLSX
2018Co-Authors: Ryan D Heimroth, Elisa Casadei, Irene SalinasAbstract:Animal mucosal barriers constantly interact with the external environment, and this interaction is markedly different in aquatic and terrestrial environments. Transitioning from water to land was a critical step in vertebrate evolution, but the immune adaptations that mucosal barriers such as the skin underwent during that process are essentially unknown. Vertebrate animals such as the African lungfish have a bimodal life, switching from freshwater to terrestrial habitats when environmental conditions are not favorable. African lungfish skin mucus secretions contribute to the terrestrialization process by forming a cocoon that surrounds and protects the lungfish body. The goal of this study was to characterize the skin mucus immunoproteome of African lungfish, Protopterus dolloi, before and during the Induction Phase of terrestrialization as well as the immunoproteome of the gill mucus during the terrestrialization Induction Phase. Using LC-MS/MS, we identified a total of 974 proteins using a lungfish Illumina RNA-seq database, 1,256 proteins from previously published lungfish sequence read archive and 880 proteins using a lungfish 454 RNA-seq database for annotation in the three samples analyzed (free-swimming skin mucus, terrestrialized skin mucus, and terrestrialized gill mucus). The terrestrialized skin mucus proteome was enriched in proteins with known antimicrobial functions such as histones and S100 proteins compared to free-swimming skin mucus. In support, gene ontology analyses showed that the terrestrialized skin mucus proteome has predicted functions in processes such as viral process, defense response to Gram-negative bacterium, and tumor necrosis factor-mediated signaling. Importantly, we observed a switch in immunoglobulin heavy chain secretion upon terrestrialization, with IgW1 long form (IgW1L) and IgM1 present in free-swimming skin mucus and IgW1L, IgM1, and IgM2 in terrestrialized skin mucus. Combined, these results indicate an increase in investment in the production of unique immune molecules in P. dolloi skin mucus in response to terrestrialization that likely better protects lungfish against external aggressors found in land.
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Data_Sheet_4_Effects of Experimental Terrestrialization on the Skin Mucus Proteome of African Lungfish (Protopterus dolloi).XLSX
2018Co-Authors: Ryan D Heimroth, Elisa Casadei, Irene SalinasAbstract:Animal mucosal barriers constantly interact with the external environment, and this interaction is markedly different in aquatic and terrestrial environments. Transitioning from water to land was a critical step in vertebrate evolution, but the immune adaptations that mucosal barriers such as the skin underwent during that process are essentially unknown. Vertebrate animals such as the African lungfish have a bimodal life, switching from freshwater to terrestrial habitats when environmental conditions are not favorable. African lungfish skin mucus secretions contribute to the terrestrialization process by forming a cocoon that surrounds and protects the lungfish body. The goal of this study was to characterize the skin mucus immunoproteome of African lungfish, Protopterus dolloi, before and during the Induction Phase of terrestrialization as well as the immunoproteome of the gill mucus during the terrestrialization Induction Phase. Using LC-MS/MS, we identified a total of 974 proteins using a lungfish Illumina RNA-seq database, 1,256 proteins from previously published lungfish sequence read archive and 880 proteins using a lungfish 454 RNA-seq database for annotation in the three samples analyzed (free-swimming skin mucus, terrestrialized skin mucus, and terrestrialized gill mucus). The terrestrialized skin mucus proteome was enriched in proteins with known antimicrobial functions such as histones and S100 proteins compared to free-swimming skin mucus. In support, gene ontology analyses showed that the terrestrialized skin mucus proteome has predicted functions in processes such as viral process, defense response to Gram-negative bacterium, and tumor necrosis factor-mediated signaling. Importantly, we observed a switch in immunoglobulin heavy chain secretion upon terrestrialization, with IgW1 long form (IgW1L) and IgM1 present in free-swimming skin mucus and IgW1L, IgM1, and IgM2 in terrestrialized skin mucus. Combined, these results indicate an increase in investment in the production of unique immune molecules in P. dolloi skin mucus in response to terrestrialization that likely better protects lungfish against external aggressors found in land.
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Image_1_Effects of Experimental Terrestrialization on the Skin Mucus Proteome of African Lungfish (Protopterus dolloi).TIFF
2018Co-Authors: Ryan D Heimroth, Elisa Casadei, Irene SalinasAbstract:Animal mucosal barriers constantly interact with the external environment, and this interaction is markedly different in aquatic and terrestrial environments. Transitioning from water to land was a critical step in vertebrate evolution, but the immune adaptations that mucosal barriers such as the skin underwent during that process are essentially unknown. Vertebrate animals such as the African lungfish have a bimodal life, switching from freshwater to terrestrial habitats when environmental conditions are not favorable. African lungfish skin mucus secretions contribute to the terrestrialization process by forming a cocoon that surrounds and protects the lungfish body. The goal of this study was to characterize the skin mucus immunoproteome of African lungfish, Protopterus dolloi, before and during the Induction Phase of terrestrialization as well as the immunoproteome of the gill mucus during the terrestrialization Induction Phase. Using LC-MS/MS, we identified a total of 974 proteins using a lungfish Illumina RNA-seq database, 1,256 proteins from previously published lungfish sequence read archive and 880 proteins using a lungfish 454 RNA-seq database for annotation in the three samples analyzed (free-swimming skin mucus, terrestrialized skin mucus, and terrestrialized gill mucus). The terrestrialized skin mucus proteome was enriched in proteins with known antimicrobial functions such as histones and S100 proteins compared to free-swimming skin mucus. In support, gene ontology analyses showed that the terrestrialized skin mucus proteome has predicted functions in processes such as viral process, defense response to Gram-negative bacterium, and tumor necrosis factor-mediated signaling. Importantly, we observed a switch in immunoglobulin heavy chain secretion upon terrestrialization, with IgW1 long form (IgW1L) and IgM1 present in free-swimming skin mucus and IgW1L, IgM1, and IgM2 in terrestrialized skin mucus. Combined, these results indicate an increase in investment in the production of unique immune molecules in P. dolloi skin mucus in response to terrestrialization that likely better protects lungfish against external aggressors found in land.
Jang Hern Lee - One of the best experts on this subject based on the ideXlab platform.
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inhibition of cytochrome p450 side chain cleavage attenuates the development of mechanical allodynia by reducing spinal d serine production in a murine model of neuropathic pain
Frontiers in Pharmacology, 2019Co-Authors: Sheu Ran Choi, Alvin J Beitz, Jang Hern LeeAbstract:Research indicates that neurosteroids are locally synthesized in the central nervous system and play an important modulatory role in nociception. While the neurosteroidogenic enzyme, cytochrome P450 side-chain cleavage enzyme (P450scc), is the initiating enzyme of steroidogenesis, P450scc has not been examined under the pathophysiological conditions associated with peripheral neuropathy. Thus, we investigated whether chronic constriction injury (CCI) of the sciatic nerve increases the expression of P450scc in the spinal cord and whether this increase modulates serine racemase (Srr) expression and D-serine production contributing to the development of neuropathic pain. CCI increased the immunoreactivity of P450scc in astrocytes of the ipsilateral lumbar spinal cord dorsal horn. Intrathecal administration of the P450scc inhibitor, aminoglutethimide, during the Induction Phase of neuropathic pain (days 0 to 3 post-surgery) significantly suppressed the CCI-induced development of mechanical allodynia and thermal hyperalgesia, the increased expression of astrocyte Srr in both the total and cytosol levels, and the increases in D-serine immunoreactivity at day 3 post-surgery. By contrast, intrathecal administration of aminoglutethimide during the maintenance Phase of pain (days 14 to 17 post-surgery) had no effect on the developed neuropathic pain nor the expression of spinal Srr and D-serine immunoreactivity at day 17 post-surgery. Intrathecal administration of exogenous D-serine during the Induction Phase of neuropathic pain (days 0 to 3 post-surgery) restored the development of mechanical allodynia, but not the thermal hyperalgesia, that were suppressed by aminoglutethimide administration. Collectively, these results demonstrate that spinal P450scc increases the expression of astrocyte Srr and D-serine production, ultimately contributing to the development of mechanical allodynia induced by peripheral nerve injury.
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sigma 1 receptor mediated increase in spinal p38 mapk phosphorylation leads to the Induction of mechanical allodynia in mice and neuropathic rats
Experimental Neurology, 2013Co-Authors: Jiyoung Moon, Seo Yeon Yoon, Alvin J Beitz, Sheu Ran Choi, Dae Hyun Roh, Suk Yun Kang, Soon Gu Kwon, Hoon Seong Choi, Ho Jae Han, Jang Hern LeeAbstract:The direct activation of the spinal sigma-1 receptor (Sig-1R) produces mechanical allodynia (MA) and thermal hyperalgesia (TH) in mice. In addition, the blockade of the spinal Sig-1R prevents the Induction of MA, but not TH in chronic constriction injury (CCI)-induced neuropathic rats. The present study was designed to investigate whether the increase in spinal p38 MAPK phosphorylation (p-p38 MAPK) mediates Sig-1R-induced MA or TH in mice and the Induction of MA in neuropathic rats. MA and TH were evaluated using von Frey filaments and a hot-plate apparatus, respectively. Neuropathic pain was produced by CCI of the right sciatic nerve in rats. Western blot assay and immunohistochemistry were performed to determine the changes of p-p38 MAPK expression in the spinal cord. Intrathecal (i.t.) injection of PRE084, a selective Sig-1R agonist, into naive mice time-dependently increased the expression of p-p38 MAPK, which was blocked by pretreatment with BD1047, a Sig-1R antagonist. I.t. pretreatment with SB203580, a p38 MAPK inhibitor also dose-dependently inhibited PRE084-induced MA, whereas TH Induction was not affected. In CCI rats, i.t. injection of BD1047 during the Induction Phase (postoperative days 0 to 5) reduced the CCI-induced increase in p-p38 MAPK. In addition, i.t. SB203580 treatment during the Induction Phase also suppressed the development of CCI-induced MA, but not TH. Conversely, i.t. SB203580 treatment during the maintenance Phase (postoperative days 15 to 20) had no effect on CCI-induced MA or TH. These results demonstrate that the increase in spinal p-p38 MAPK is closely associated with the Induction of Sig-1R mediated MA, but not TH. Sigma-1 receptor modulation of p-p38 MAPK also plays an important role in the Induction, but not the maintenance, of MA in neuropathic pain.
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spinal sigma 1 receptors activate nadph oxidase 2 leading to the Induction of pain hypersensitivity in mice and mechanical allodynia in neuropathic rats
Pharmacological Research, 2013Co-Authors: Sheu Ran Choi, Seo Yeon Yoon, Alvin J Beitz, Dae Hyun Roh, Suk Yun Kang, Jiyoung Moon, Soon Gu Kwon, Hoon Seong Choi, Ho Jae Han, Jang Hern LeeAbstract:We have recently demonstrated that spinal sigma-1 receptors (Sig-1Rs) mediate pain hypersensitivity in mice and neuropathic pain in rats. In this study, we examine the role of NADPH oxidase 2 (Nox2)-induced reactive oxygen species (ROS) on Sig-1R-induced pain hypersensitivity and the Induction of chronic neuropathic pain. Neuropathic pain was produced by chronic constriction injury (CCI) of the right sciatic nerve in rats. Mechanical allodynia and thermal hyperalgesia were evaluated in mice and CCI-rats. Western blotting and dihydroethidium (DHE) staining were performed to assess the changes in Nox2 activation and ROS production in spinal cord, respectively. Direct activation of spinal Sig-1Rs with the Sig-1R agonist, PRE084 induced mechanical allodynia and thermal hyperalgesia, which were dose-dependently attenuated by pretreatment with the ROS scavenger, NAC or the Nox inhibitor, apocynin. PRE084 also induced an increase in Nox2 activation and ROS production, which were attenuated by pretreatment with the Sig-1R antagonist, BD1047 or apocynin. CCI-induced nerve injury produced an increase in Nox2 activation and ROS production in the spinal cord, all of which were attenuated by intrathecal administration with BD1047 during the Induction Phase of neuropathic pain. Furthermore, administration with BD1047 or apocynin reversed CCI-induced mechanical allodynia during the Induction Phase, but not the maintenance Phase. These findings demonstrate that spinal Sig-1Rs modulate Nox2 activation and ROS production in the spinal cord, and ultimately contribute to the Sig-1R-induced pain hypersensitivity and the peripheral nerve injury-induced Induction of chronic neuropathic pain.
Yoshinobu Okuda - One of the best experts on this subject based on the ideXlab platform.
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il 6 plays a crucial role in the Induction Phase of myelin oligodendrocyte glycoprotein 35 55 induced experimental autoimmune encephalomyelitis
Journal of Neuroimmunology, 1999Co-Authors: Yoshinobu Okuda, Saburo Sakoda, Harutoshi Fujimura, Yukihiko Saeki, T Kishimoto, Takehiko YanagiharaAbstract:Abstract We investigated the role of IL-6 in myelin oligodendrocyte glycoprotein (MOG) peptide induced experimental autoimmune encephalomyelitis (EAE) using IL-6-deficient mice and found that IL-6-deficient mice were resistant to active Induction of EAE, but that the treatment of those mice with IL-6 during the preclinical Phase caused typical EAE. We also found that both wild-type and IL-6-deficient mice were resistant to passive transfer of EAE by lymphocytes from IL-6-deficient mice, but that passive transfer of lymphocytes from wild-type mice induced typical EAE in IL-6-deficient mice. Histological abnormalities of the central nervous system (CNS) in those IL-6-deficient mice with EAE were similar to those in wild-type mice with EAE. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed no difference in the production of inflammatory cytokines such as IL-1β, IL-2, TNF-α, and IFN-γ in the CNS of IL-6-deficient mice with EAE as compared to the CNS of wild-type mice with EAE. These results indicated that IL-6 might be an important factor in the Induction Phase, but might have little influence on the effector Phase of EAE. We further estimated the production of cytokines in MOG-stimulated lymph node (LN) cells by enzyme-linked immunosorbent assay. Increased IL-4 and IL-10 production and reduced IL-2 and IFN-γ production were observed in LN cells from IL-6-deficient mice as compared to LN cells from wild-type mice. These results suggested that a shift of T cell responses from Th1 to Th2 might explain the resistance of IL-6-deficient mice to EAE. Taken together, IL-6 may play a crucial role in the Induction Phase of EAE by modulating Th1/Th2 balance.
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il 6 plays a crucial role in the Induction Phase of myelin oligodendrocyte glycoprotein 35 55 induced experimental autoimmune encephalomyelitis
Journal of Neuroimmunology, 1999Co-Authors: Yoshinobu Okuda, Saburo Sakoda, Harutoshi Fujimura, Yukihiko Saeki, T Kishimoto, Takehiko YanagiharaAbstract:We investigated the role of IL-6 in myelin oligodendrocyte glycoprotein (MOG) peptide induced experimental autoimmune encephalomyelitis (EAE) using IL-6-deficient mice and found that IL-6-deficient mice were resistant to active Induction of EAE, but that the treatment of those mice with IL-6 during the preclinical Phase caused typical EAE. We also found that both wild-type and IL-6-deficient mice were resistant to passive transfer of EAE by lymphocytes from IL-6-deficient mice, but that passive transfer of lymphocytes from wild-type mice induced typical EAE in IL-6-deficient mice. Histological abnormalities of the central nervous system (CNS) in those IL-6-deficient mice with EAE were similar to those in wild-type mice with EAE. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed no difference in the production of inflammatory cytokines such as IL-1beta, IL-2, TNF-alpha, and IFN-gamma in the CNS of IL-6-deficient mice with EAE as compared to the CNS of wild-type mice with EAE. These results indicated that IL-6 might be an important factor in the Induction Phase, but might have little influence on the effector Phase of EAE. We further estimated the production of cytokines in MOG-stimulated lymph node (LN) cells by enzyme-linked immunosorbent assay. Increased IL-4 and IL-10 production and reduced IL-2 and IFN-gamma production were observed in LN cells from IL-6-deficient mice as compared to LN cells from wild-type mice. These results suggested that a shift of T cell responses from Thl to Th2 might explain the resistance of IL-6-deficient mice to EAE. Taken together, IL-6 may play a crucial role in the Induction Phase of EAE by modulating Th1/Th2 balance.