Interleukin-1β (IL-1β)-induced modulation of the hypothalamic IL-1β system,tumor necrosis factor-α, and transforming growth factor-β1 mRNAs in obese (fa/fa) and lean (Fa/Fa) Zucker rats: Implications to IL-1β feedback systems and cytokine–cytokine interactions

Interleukin-1β (IL-1β) induces anorexia, fever, sleep changes, and neuroendocrine alterations when administered into the brain. Here, we investigated the regulation of the IL-1β system (ligand, receptors, receptor accessory protein, and receptor antagonist), tumor necrosis factor-α (TNF-α), transforming growth factor (TGF)-β1, and TGF-α mRNAs in the hypothalamus of obese (fa/fa) and lean (Fa/Fa) Zucker rats in response to the intracerebroventricular microinfusion of IL-1β (8.0 ng/24 hr for 72 hr, a dose that yields estimated pathophysiological concentrations in the cerebrospinal fluid). IL-1β increased IL-1β, IL-1 receptor types I and II (IL-1RI and IL-1RII), IL-1 receptor accessory protein soluble form (IL-1R AcP II), IL-1 receptor antagonist (IL-1Ra), TNF-α, and TGF-β1 mRNAs in the hypothalamus from obese and lean rats. IL-1β–induced IL-1β system and ligand (IL-1β, TNF-α, and TGF-β1) mRNA profiles were highly intercorrelated in the same samples. Levels of membrane-bound IL-1R AcP and TGF-α mRNAs did not change. Heat-inactivated IL-1β had no effect. The data suggest 1) the operation of an IL-1β feedback system (IL-1β/IL-1RI/IL-1R Acp II/IL-1RII/IL-1Ra) and 2) potential cytokine–cytokine interactions with positive (IL-1β ←→ TNF-α) and negative (TGF-β1 → IL-1β/TNF-α) feedback. Dysregulation of the IL-1β feedback system and the TGF-β1/IL-1β-TNF-α balance may have implications for neurological disorders associated with high levels of IL-1β in the brain. J. Neurosci. Res. 49:541–550, 1997. © 1997 Wiley-Liss, Inc.     

Interleukin-1α (IL-1α), IL-1β, IL-1 receptor type I, IL-1 receptor antagonist, and TGF-β1 mRNAs in pediatric astrocytomas, ependymomas, and primitive neuroectodermal tumors

Interleukin-1α (IL-1α), IL-1β, interleukin-1 receptor type I (IL-1RI, signaling receptor), and IL-1 receptor antagonist (IL-1Ra, endogenous inhibitor) are pivotal components of the IL-1 system. IL-1 and other cytokines induced by IL-1, such as TGF-β1, may participate in the growth of various tumor cells. In children, primary nervous system tumors represent the most common solid malignancy. We investigated the levels of IL-1α, IL-1β, IL-1RI, IL-1Ra, and TGF-β1 mRNAs in pediatric astrocytomas (n=19), ependymomas (n=13), and primitive neuroectodermal tumors (n=22) using sensitive and specific RNase protection assays. The data show a significant distinct cytokine mRNA profile among brain tumor types. Pilocytic, nonpilocytic, and anaplastic astrocytomas have significant increased levels of IL-1β, IL-1RI, and TGF-β1 mRNAs, but low levels of IL-1Ra mRNA; this may have implications for an IL-1β feedback system and IL-1β?TGF-β1 interactions in astrocytomas. Ependymomas show increased levels of IL-1α and IL-1β mRNAs associated with low levels of IL-1Ra mRNA; primitive neuroectodermal tumors do not exhibit increased levels of any cytokine component examined. The data also suggest that a dysregulation of the balance between stimulatory and inhibitory cytokines may be involved in the growth and development of brain tumors via autocrine/paracrine mechanisms.     

Interleukin 1-β- and tumor necrosis factor-α-mediated regulation of ICAM-1 gene expression in astrocytes requires protein kinase C activity

Several adhesion molecules including intracellular adhesion molecule-1 (ICAM-1) are expressed by astrocytes, the predominant glial cell of the central nervous system (CNS). Such molecules are important in the trafficking of leukocytes to sites of inflammation, and in lymphocyte activation. ICAM-1 is constitutively expressed by neonatal rat astrocytes, and expression is enhanced by the proinflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), with IL-1β and TNF-α being the strongest inducers. In this study, we have examined the nature of the second messengers involved in ICAM-1 gene expression induced by the cytokines IL-1β and TNF-α. Our results indicate that stimuli related to protein kinase C (PKC) such as the phorbol ester phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187 increase ICAM-1 mRNA expression, whereas cyclic nucleotide analogs and PKA agonists have no effect. Pharmacologic inhibitors of PKC such as H7, H8, and calphostin C inhibit ICAM-1 gene expression inducible by IL-1β and TNF-α. Prolonged treatment of astrocytes with PMA results in a time-dependent downregulating of the PKC isoforms α, δ, and ?, and a concomitant diminution of ICAM-1 mRNA expression induced by IL-1β, TNF-α, and PMA itself at specific time points post-PMA treatment. These data, collectively, demonstrate a role for various PKC isoforms in IL-1β and TNF-α enhancement of ICAM-1 gene expression in rat astrocytes. © 1995 Wiley-Liss, Inc.     

Comparative distribution of estrogen receptor-α and -β mRNA in the rat central nervous system

Estrogen plays a profound role in regulating the structure and function of many neuronal systems in the adult rat brain. The actions of estrogen were thought to be mediated by a single nuclear estrogen receptor (ER) until the recent cloning of a novel ER (ER-β). To ascertain which ER is involved in the regulation of different brain regions, the present study compared the distribution of the classical (ER-α) and novel (ER-β) forms of ER mRNA-expressing neurons in the central nervous system (CNS) of the rat with in situ hybridization histochemistry. Female rat brain, spinal cord, and eyes were frozen, and cryostat sections were collected on slides, hybridized with [³⁵S]-labeled antisense riboprobes complimentary to ER-α or ER-β mRNA, stringently washed, and opposed to emulsion. The results of these studies revealed the presence of ER-α and ER-β mRNA throughout the rostral-caudal extent of the brain and spinal cord. Neurons of the olfactory bulb, supraoptic, paraventricular, suprachiasmatic, and tuberal hypothalamic nuclei, zona incerta, ventral tegmental area, cerebellum (Purkinje cells), laminae III–V, VIII, and IX of the spinal cord, and pineal gland contained exclusively ER-β mRNA. In contrast, only ER-α hybridization signal was seen in the ventromedial hypothalamic nucleus and subfornical organ. Perikarya in other brain regions, including the bed nucleus of the stria terminalis, medial and cortical amygdaloid nuclei, preoptic area, lateral habenula, periaqueductal gray, parabrachial nucleus, locus ceruleus, nucleus of the solitary tract, spinal trigeminal nucleus and superficial laminae of the spinal cord, contained both forms of ER mRNA. Although the cerebral cortex and hippocampus contained both ER mRNAs, the hybridization signal for ER-α mRNA was very weak compared with ER-β mRNA. The results of these in situ hybridization studies provide detailed information about the distribution of ER-α and ER-β mRNAs in the rat CNS. In addition, this comparative study provides evidence that the region-specific expression of ER-α, ER-β, or both may be important in determining the physiological responses of neuronal populations to estrogen action. J. Comp. Neurol. 388:507–525, 1997. © 1997 Wiley-Liss, Inc.     

Differential localization and expression of α and β isoenzymes of protein kinase c in the rat retina

Expression and cellular localization of three isoenzymes of Ca²⁺-dependent protein kinase C (PKCα, PKCβ, and PKCγ) in the adult rat retina were revealed by immunohistochemistry and in situ hybridization histochemistry with isoenzyme-specific antibodies and cRNA probes. Immunoreactivities and mRNA signals for PKCα were conspicuous in rod bipolar cells. A subgroup of amacrine cells expressed PKCα. The cells in the ganglion cell layer also displayed PKCα gene products. Positive immunoreactivities for PKCβ were localized as stripe patterns in the inner plexiform layer, corresponding to the stratification levels of axon terminals of cone bipolar cells. The somata of cone bipolar cells expressed PKCβ. Amacrine cells and retinal ganglion cells also displayed PKCβ gene products. The results obtained by immunohistochemistry were confirmed with colocalization of mRNA signals for PKCα and PKCβ on the somata. The cell membranes showed stronger immunoreactivities than did the cytoplasms for both PKCα and PKCβ. Neither immunoreactivities nor mRNA signals for PKCγ were detected in all retinal regions. The differential roles of Ca²⁺-dependent PKC isoenzymes could be revealed in physiological defined retinal neurons. J. Neurosci. Res. 54:655–663, 1998. © 1998 Wiley-Liss, Inc.     

Implication of Akt‐dependent Prp19α/14‐3‐3β/Cdc5L complex formation in neuronal differentiation

PRP19α and CDC5L are major components of the active spliceosome. However, their association process is still unknown. Here, we demonstrated that PRP19α/14‐3‐3β/CDC5L complex formation is regulated by Akt during nerve growth factor (NGF)‐induced neuronal differentiation of PC12 cells. Analysis of PRP19α mutants revealed that the phosphorylation of PRP19α at Thr 193 by Akt was critical for its binding with 14‐3‐3β to translocate into the nuclei and for PRP19α/14‐3‐3β/CDC5L complex formation in neuronal differentiation. Forced expression of either sense PRP19α or sense 14‐3‐3β RNAs promoted NGF‐induced neuronal differentiation, whereas down‐regulation of these mRNAs showed a suppressive effect. The nonphosphorylation mutant PRP19αT193A lost its binding ability with 14‐3‐3β and acted as a dominant‐negative mutant in neuronal differentiation. These results imply that Akt‐dependent phosphorylation of PRP19α at Thr193 triggers PRP19α/14‐3‐3β/CDC5L complex formation in the nuclei, likely to assemble the active spliceosome against neurogenic pre‐mRNAs. © 2010 Wiley‐Liss, Inc.     

Induction of human immunodeficiency virus type 1 replication in human glial cells after proinflammatory cytokines stimulation: Effect of IFNγ, IL1β, and TNFα on differentiation and chemokine production in glial cells

Although evidence for human immunodeficiency virus 1 (HIV-1) presence in the central nervous system (CNS) of infected patients is well established, the intensity of viral replication within the brain is not usually known. In vitro, human embryonic microglial cells internalized HIV-1 through a CD4-dependent pathway but were not permissive to viral replication. We observed that HIV replication was induced when CNS cell cultures were stimulated for 14 days by a combination of proinflammatory cytokines including IFNγ, IL1β, and TNFα. After long-term cytokine stimulation, morphologically differentiated glial cells appeared, in which HIV-1 tat antigen was detected after infection. Thus, variations in the stage of maturation/activation of CNS cells under inflammatory conditions probably play a major role in facilitating massive production of HIV-1. We then studied the effect of prolonged cytokine stimulation on the secretion of inflammatory mediators by glial cells. An early increased secretion of prostaglandin F2α and chemokines (RANTES>>MIP-1α>>MIP-1β) was observed, due to both microglia and astrocytes. In contrast to persistent PGF2α production, an extinction of RANTES and MIP-1β but not of MIP-1α secretion occurred during the 14 days of stimulation and was inversely correlated with the ability of glial cells to replicate HIV-1. The study of the secretory factors produced in response to a persistent inflammation could provide a better understanding of the modulation of HIV replication in glial cells. GLIA 23:304–315, 1998. © 1998 Wiley-Liss, Inc.     

Brain protein phosphatase 2A: Developmental regulation and distinct cellular and subcellular localization by B subunits

Protein phosphatase 2A (PP2A) is a heterotrimeric enzyme consisting of a catalytic subunit (C), a structural subunit (A), and a variable regulatory subunit (B). We have investigated the spatial and temporal expression patterns of three members of the B subunit family, Bα, Bβ, and Bγ, both at the message level by using ribonuclease protection analysis and at the protein level by using specific antibodies. Although A, Bα, and C protein are expressed in many tissues, Bβ and Bγ were detectable only in brain. Bα, Bβ, and Bγ are components of the brain PP2A heterotrimer, because they copurified with A and C subunits on immobilized microcystin. Whereas Bα and Bβ are mainly cytosolic, Bγ is enriched in the cytoskeletal fraction. In contrast to A, C, and Bα, which are expressed at constant levels, Bβ and Bγ RNA and protein are developmentally regulated, with Bβ levels decreasing and Bγ levels increasing sharply after birth. RNA and immunoblot analyses of subdissected brain regions as well as immunohistochemistry demonstrated that B subunits are expressed in distinct but overlapping neuronal populations and cellular domains. These data indicate that B subunits confer tissue and cell specificity, subcellular localization, and developmental regulation to the PP2A holoenzyme. The Bα-containing heterotrimer may be important in general neuronal functions that involve its partially nuclear localization. Holoenzymes containing Bβ likely function in early brain development as well as in somata and processes of subsets of mature neurons. Bγ may target PP2A to cytoskeletal substrates that are important in the establishment and maintenance of neuronal connections. J. Comp. Neurol. 392:515–527, 1998. © 1998 Wiley-Liss, Inc.     

Constitutive and LPS-regulated expression of interleukin-18 receptor beta variants in the mouse brain

Interleukin (IL)-18 is a pro-inflammatory cytokine that is proposed to be involved in physiological as well as pathological conditions in the adult brain. IL-18 acts through a heterodimer receptor comprised of a subunit alpha (IL-18Rα) required for binding, and a subunit beta (IL-18Rβ) necessary for activation of signal transduction. We recently demonstrated that the canonical alpha binding chain, and its putative decoy isoform, are expressed in the mouse central nervous system (CNS) suggesting that IL-18 may act on the brain by directly binding its receptor.Considering that the co-expression of the beta chain seems to be required to generate a functional receptor and, a short variant of this chain has been described in rat and human brain, in this study we have extended our investigation to IL-18Rβ in mouse.Using a multi-methodological approach we found that: (1) a short splice variant of IL-18Rβ was expressed in the CNS even if at lower levels compared to the full-length IL-18Rβ variants, (2) the canonical IL-18Rβ is expressed in the CNS particularly in areas and nuclei belonging to the limbic system as previously observed for IL-18Rα and finally (3) we have also demonstrated that both IL-18Rβ isoforms are up-regulated in different brain areas three hours after a single lipopolysaccharide (LPS) injection suggesting that IL-18Rβ in the CNS might be involved in mediating the endocrine and behavioral effects of LPS.Our data highlight the considerable complexity of the IL-18 regulation activity in the mouse brain and further support an important central role for IL-18.     

Changes of the expression and distribution of retinoic acid receptors during neurogenesis in mouse embryos

The expression and distribution of three retinoic acid receptors, α, β and γ, were investigated in the CNS of mouse embryos during development. mRNAs and proteins of RAR-β that were expressed in the spinal cord of the 12.5-day mouse embryo decreased during development but they were not decreased in the brain. The RAR-β-positive cells were already present in the ventral region of the spinal cord of 10.5-day mouse embryos, gradually appeared in the dorsal region during development and then disappeared from the spinal cord after birth. In the brain, RAR-β-positive cells were detected in the mesencephalon and rhombencephalon but not in the telencephalon of the 12.5-day mouse embryos. RAR-β-positive cells were present in the hippocampus and cingulum but not in the neocortex of 14.5-day mouse embryos. Most neurons in the hippocampus of 16.5-day mouse embryos and the cortex of newborn mice were RAR-β-positive. In the spinal cord, RAR-α mRNAs and proteins also decreased during development but more gradually than RAR-β mRNAs and proteins. During development, the distributions of RAR-α and -β in the spinal cord and brain did not differ substantially. The main difference was the appearance of a subtypes of RAR-α, a 52-kDa protein, in the brain of newborn mice. On the other hand, RAR-γ proteins were only faintly detected in the spinal cord and the brain of the mice during the embryonal stages but these increased after birth. The distribution of RAR-α- or -β-positive cells were consistent with the neurogenesis during development in the spinal cord and brain.     

Interleukin-1 and tumor necrosis factor-mediated regulation of C3 gene expression in human astroglioma cells

In this report, we show that in the human astroglioma cell line D54-MG, both interleukin-1 (IL-1β) and tumor necrosis factor-alpha (TNF-α) enhance C3 gene expression in a time- and dose-dependent manner. Kinetic analysis demonstrates that after 96 h, C3 mRNA levels increase approximately 30-fold and 20-fold in response to IL-1β or TNF-α, respectively. C3 protein production increases proportionally, reaching levels 36-fold and 18-fold higher than untreated controls upon exposure to IL-1β or TNF-α, respectively. D54-MG cells require a minimal 1 h exposure to IL-1β in order to enhance C3 gene expression significantly, while 4 to 8 h are required for TNF-α. Simultaneous treatment of D54-MG cells with IL-1β and interferon-gamma (IFN-γ) resulted in an additive increase in both C3 mRNA and protein expression, a finding not seen with the combination of TNF-α and IFN-γ. Primary rat astrocytes also express increased C3 mRNA levels after 48 h in response to IL-1β (5.3-fold increase) and TNF-α (7-fold increase), while an additive effect was observed upon simultaneous treatment with both IL-1β and IFN-γ. In the central nervous system (CNS), endogenous complement and cytokine production by astrocytes, and enhancement by IFN-γ, a product of activated T cells often seen in the CNS in neural autoimmune disease, may contribute to the pathogenesis of inflammatory demyelinating diseases such as multiple sclerosis.     

Lack of effect of interleukins 1α and 1β, during in vitro perifusion,on anterior pituitary release of adrenocorticotropic hormone and β endorphin in the male rat

It has been demonstrated that interleukin 1 (IL1) injection provokes a great variety of biological effects, notably an activation of the corticotropic axis, increasing plasma adrenocorticotropic hormone (ACTH) and corticosterone. However, the primary site of action of IL1 is still controversial. In the present study, we first verified the in vivo capability of human interleukins 1α (hIL1α) and 1β (hIL1β) to release ACTH and β endorphin (β EP) in the normal male rat, before investigating, through an anterior pituitary (AP) perifusion system, the hIL1α and hIL1β effects on basal and corticotropin-releasing factor (CRF)-induced ACTH and β EP secretions. This system enabled the examination of a dynamic profile of hormones secretion, avoiding the possibility of feedback mechanisms, as is the case with the use of regular but very often longtime incubations. The results showed that in a perifusion system, with a short duration treatment (below 2 hr) compatible with the kinetics of action observed in vivo, basal and CRF-induced ACTH and β EP release were not modified in the presence of a broad range of concentrations (from 10^?12 to 10^?9 M) of hIL1α or hIL1β. Taken together, these results clearly show that in an in vitro situation close to physiological conditions, the primary site of action of hIL1α and hIL1β on ACTH and β EP release is not located at the AP level in the male rat. © 1993 Wiley-Liss, Inc.     

Modulation of microglia by stem cell factor

We reported previously that stem cell factor (SCF) is produced mainly by neurons and that its receptor (c-kitR), encoded by the protooncogene c-kit, is expressed in microglia, suggesting that SCF/c-kitR signaling may be involved in neuron-microglia interactions. We now report that SCF supports microglial survival in cultures, maintains them in process-bearing morphology, and inhibits microglial proliferation induced by colony stimulating factor-1. SCF potentiates microglial expression of the mRNAs of nerve growth factor, brain-derived neurotrophic factor and ciliary neurotrophic factor, and downregulates microglial expression of the inflammation-associated cytokines, tumor necrosis factor-a (TNF-α), and interleukin-1β (IL-1β). SCF potentiates lipopolysaccharide-stimulated, but attenuates interferon-γ TFNα mediated expression of the mRNAs of IL-1β and TNF-α. The SCF-induced expression of neurotrophin mRNAs is enhanced by the addition of lipopolysaccharide (LPS) but is reduced by IFNγ. The interactions between SCF and LPS or IFNγ in the regulation of inflammation-associated cytokine gene expression are accompanied by the differential regulation of c-kitR in microglia. These observations suggest that SCF/c-kitR signaling modulates microglial activity. J. Neurosci. Res. 53:29–37, 1998. © 1998 Wiley-Liss, Inc.     

Binding and uptake of Aβ1‐42 by primary human astrocytes in vitro

Clearance of the amyloid‐β peptide (Aβ) as a remedy for Alzheimer's disease (AD) is a major target in on‐going clinical trials. In vitro studies confirmed that Aβ is taken up by rodent astrocytes, but knowledge on human astrocyte‐mediated Aβ clearance is sparse. Therefore, by means of flow cytometry and confocal laser scanning microscopy (CLSM), we evaluated the binding and internalization of Aβ1‐42 by primary human fetal astrocytes and adult astrocytes, isolated from nondemented subjects (n = 8) and AD subjects (n = 6). Furthermore, we analyzed whether α1‐antichymotrypsin (ACT), which is found in amyloid plaques and can influence Aβ fibrillogenesis, affects the Aβ uptake by human astrocytes. Upon over night exposure of astrocytes to FAM‐labeled Aβ1‐42 (10 μM) preparations, (80.7 ± 17.7)% fetal and (52.9 ± 20.9)% adult Aβ‐positive astrocytes (P = 0.018) were observed. No significant difference was found in Aβ1‐42 uptake between AD and non‐AD astrocytes, and no influence of ApoE genotype on Aβ1‐42 uptake was observed in any group. There was no difference in the percentage of Aβ‐positive cells upon exposure to Aβ1‐42 (10 μM) combined with ACT (1,000:1, 100:1, and 10:1 molar ratio), versus Aβ1‐42 alone. CLSM revealed binding of Aβ1‐42 to the cellular surfaces and cellular internalization of smaller Aβ1‐42 fragments. Under these conditions, there was no increase in cellular release of the proinflammatory chemokine monocyte‐chemoattractant protein 1, as compared with nontreated control astrocytes. Thus, primary human astrocytes derived from different sources can bind and internalize Aβ1‐42, and fetal astrocytes were more efficient in Aβ1‐42 uptake than adult astrocytes. © 2008 Wiley‐Liss, Inc.     

Stimulation of group II phospholipase A2 mRNA expression and release in an immortalized astrocyte cell line (DITNC) by LPS,TNFα, and IL-1β

Astrocytes are immunoactive cells in brain and have been implicated in the defense mechanism in response to external injury. Previous studies using cultured glial cells indicated the ability of astrocytes to respond to bacteria endotoxin and cytokines, resulting in the release of phospholipase A₂. In this study, we examined the interactive effects of lipopolysaccharides (LPS), interleukin 1β (IL-1β) and tumor necrosis factor (TNFα) to stimulate phospholipase A₂ (PLA₂) in an immortalized astrocyte cell line (DITNC) with many properties of type I astrocytes. Northern blot analysis using oligonucleotide probes derived from the cDNA encoding the rat spleen group II PLA₂ indicated the ability of DITNC cells to respond to all three factors in the induction of gene expression and the release of PLA₂. After an initial lag time of 2 h, PLA₂ release was proportional to time, reaching a plateau by 12 h. This event occurred at a time period preceding any signs of cell death. Cycloheximide at 1.25 μM completely inhibited cytokine-induced PLA₂ release. When suboptimal amounts of TNFα were added to the DITNC culture together with IL-1β or LPS, a synergistic increase in the induction of PLA₂ release could be observed. On the other hand, combination of IL-1β and LPS resulted only in an additive increase in PLA₂ release. Antibodies to IL-1β and TNFα completely neutralized the effects of these two agents on PLA₂ release. However, neither antibody was able to inhibit the PLA₂ release induced by LPS, suggesting that the effect of LPS was not complicated by the release of IL-1β or TNFα. Taken together, results show that the immortalized astrocyte cell line (DITNC) can be used for studies to elucidate the molecular mechanism underlying the cytokine signaling cascade and subsequent induction of PLA₂ synthesis.     

黄芩苷对海人酸致痫小鼠海马白细胞介素-1β及肿瘤坏死因子-α表达的影响

目的 探讨黄芩苷对海人酸诱导的小鼠癫痫持续状态后海马组织白细胞介素-1 β(IL-1β)、肿瘤坏死因子-α(TNF-α)表达的影响.方法 将54只ICR雄性小鼠随机分为对照组、癫痫持续状态(SE)组、黄芩苷治疗组,每组18只.采用侧脑室注入海人酸建立小鼠癫痫持续状态模型.HE染色观察黄芩苷对小鼠癫痫持续状态后海马神经细胞的形态学影响.通过RT-PCR和Western blot分别检测小鼠海马组织中IL-1β mRNA、TNF-α mRNA及IL-1β、TNF-α蛋白的表达量.结果 黄芩苷明显改善了SE后小鼠海马组织的病理形态学,并且可降低IL-1β、TNF-α的表达(P＜0.05).结论 黄芩苷可能通过降低癫痫鼠海马组织中IL-1 β、TNF-α的表达发挥抗炎作用,从而对脑组织进行保护.     

ROCK抑制剂法舒地尔对BV2小胶质细胞极化的影响

目的 探讨Rho激酶(Rho-associated kinase,ROCK)抑制剂法舒地尔(Fasudil)对BV2小胶质细胞极化的影响.方法 免疫荧光观察细胞形态及ROCK2表达水平;乳酸脱氢酶(Lactate dehydrogenase,LDH)细胞毒性检测试剂盒检测Fasudil对细胞的毒性作用;逆转录聚合酶链反...