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1.
Neuroscience Bulletin ; (6): 1263-1277, 2023.
Artigo em Inglês | WPRIM | ID: wpr-1010615

RESUMO

The incidence rate of anxiety and depression is significantly higher in patients with inflammatory bowel diseases (IBD) than in the general population. The mechanisms underlying dextran sulfate sodium (DSS)-induced depressive-like behaviors are still unclear. We clarified that IBD mice induced by repeated administration of DSS presented depressive-like behaviors. The paraventricular thalamic nucleus (PVT) was regarded as the activated brain region by the number of c-fos-labeled neurons. RNA-sequencing analysis showed that lipocalin 2 (Lcn2) was upregulated in the PVT of mice with DSS-induced depressive behaviors. Upregulating Lcn2 from neuronal activity induced dendritic spine loss and the secreted protein induced chemokine expression and subsequently contributed to microglial activation leading to blood-brain barrier permeability. Moreover, Lcn2 silencing in the PVT alleviated the DSS-induced depressive-like behaviors. The present study demonstrated that elevated Lcn2 in the PVT is a critical factor for DSS-induced depressive behaviors.


Assuntos
Camundongos , Humanos , Animais , Lipocalina-2/genética , Núcleos da Linha Média do Tálamo , Encéfalo , Doenças Inflamatórias Intestinais , Proteínas Proto-Oncogênicas c-fos , Camundongos Endogâmicos C57BL
2.
Journal of Bone Metabolism ; : 8-15, 2016.
Artigo em Inglês | WPRIM | ID: wpr-57551

RESUMO

BACKGROUND: Lipocalin-2 (LCN2), a small glycoprotein, has a pivotal role in diverse biological processes such as cellular proliferation and differentiation. We previously reported that LCN2 is implicated in osteoclast formation induced by receptor activator of nuclear factor-kappa B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). In the present study, we used a knockout mouse model to further investigate the role of LCN2 in osteoclast development. METHODS: Osteoclastogenesis was assessed using primary bone marrow-derived macrophages. RANKL and M-CSF signaling was determined by immunoblotting, cell proliferation by bromodeoxyuridine (BrdU) enzyme-linked immunosorbent assay (ELISA), and apoptosis by cell death detection ELISA. Bone morphometric parameters were determined using a micro-computed tomography system. RESULTS: Our results showed that LCN2 deficiency increases tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclast formation in vitro, a finding that reflects enhanced proliferation and differentiation of osteoclast lineage cells. LCN2 deficiency promotes M-CSF-induced proliferation of bone marrow macrophages (BMMs), osteoclast precursors, without altering their survival. The accelerated proliferation of LCN2-deficient precursors is associated with enhanced expression and activation of the M-CSF receptor, c-Fms. Furthermore, LCN2 deficiency stimulates the induction of c-Fos and nuclear factor of activated T cells c1 (NFATc1), key transcription factors for osteoclastogenesis, and promotes RANKL-induced inhibitor of kappa B (IkappaBalpha) phosphorylation. Interestingly, LCN2 deficiency does not affect basal osteoclast formation in vivo, suggesting that LCN2 might play a role in the enhanced osteoclast development that occurs under some pathological conditions. CONCLUSIONS: Our study establishes LCN2 as a negative modulator of osteoclast formation, results that are in accordance with our previous findings.


Assuntos
Animais , Camundongos , Fosfatase Ácida , Apoptose , Fenômenos Biológicos , Medula Óssea , Bromodesoxiuridina , Morte Celular , Proliferação de Células , Ensaio de Imunoadsorção Enzimática , Glicoproteínas , Immunoblotting , Fator Estimulador de Colônias de Macrófagos , Macrófagos , Camundongos Knockout , NF-kappa B , Osteoclastos , Fosforilação , Ligante RANK , Linfócitos T , Fatores de Transcrição
3.
Chinese Pharmacological Bulletin ; (12): 565-569, 2015.
Artigo em Chinês | WPRIM | ID: wpr-465665

RESUMO

Aim To explore the effect of knockdown spinal cord LCN2 by RNAi on the development of mor-phine tolerance in normal rats.Methods After suc-cessful intrathecal implantation, fourty-eight male Sprague-Dawley rats weighing 1 80 -220 grams were randomly divided into 4 groups (n =1 2):group I:control group,group II:morphine tolerance group, group Ⅲ:mismatch siRNA group,group IV:LCN2 siRNA group.The sixth day after intrathecal implanta-tion,rats were tested to ensure the position of cathe-ters,and it was recorded as d 0.On d 2 -8,rats were subcutaneously (s.c)injected of normal saline (NS) (group I)or morphine (group Ⅱ,Ⅲ,Ⅳ)1 0 μg· g -1 twice a day at 8:00 and 1 6:00.Before everyday s. c injection,rats were intrathecally injected of 1 0 μL DEPC solution (group Ⅰ,Ⅱ),1 0 μL DEPC solution containing 4 μg mismatch siRNA (group III)and 4 μg LCN2 siRNA solution (group IV).Paw withdrawal la-tencies to thermal stimuli (PWTL)were tested before morphine injection and 45 minutes after morphine in-jection on d 1 and d 9.The percentage of maximal pos-sible effect (% MPE)was calculated later.Animals were sacrificed on d 9 after the behavioral test and the lumbar enlargement segments of the spinal cord were removed for detecting the expression of phosphorylated-p38 mitogen-activated protein kinase (p-p38 MAPK) and LCN2 by Western blot and microglia marker Iba1 by immunofluorecence.Results On d 1 ,there was no significant difference in %MPE among four groups. On d 9,compared to group Ⅰ,%MPE was signifi-cantly reduced (P <0.05)while p-p38MAPK,LCN2 and Iba1 were markedly up-regulated in group Ⅱ andⅢ (P <0.05 ).On d 9,compared to group Ⅱ,%MPE was significantly increased while p-p38MAPK, LCN2 and Iba1 were markedly reduced in group IV (P<0.05).Conclusion Using LCN2 siRNA to knock-down spinal LCN2 relieves the development of mor-phine tolerance in normal rats possibly through inhibi-ting the activation of microglia and p38 MAPK in the spinal cord.

4.
Chinese Journal of Immunology ; (12): 1036-1039,1045, 2014.
Artigo em Chinês | WPRIM | ID: wpr-599475

RESUMO

To investigate the correlation between LCN 2 or CXCL10 and experimental autoimmune encephalomyelitis(EAE),and the effect of Fluoxetine in EAE mice.Methods: Mice were randomly divided into four groups: control group, EAE group, intervention group and fluoxetine group , each group included twenty mice.EAE model were constructed with MOG35-55 in the intervention group and fluoxetine group ,following ultraviolet (UV) (280-320 nm) irradiation.Mice in fluoxetine group were given fluoxetine (10 mg/kg) by daily gavage since immunized ,and the saline was used in the control group ,intervention group and EAE group in the same way and same time.The drug/saline was continuously administered from the immunization to the day mice were sacrificed.The mean attacked time ,the nerve function grades and the incidence were observed and compared.We observed brain pathological changes by HE staining and immunohistochemistry;CXCL10 were tested by ELISA method ,and compared among the four groups.Results:The mean attacked time ,the nerve function grades and the incidence in the fluoxetine group were lower than those in the intervention group and EAE group ,there were significant differences between two groups (P<0.05),in the intervention group were lower than those in the EAE group ,there were significant differences between two groups ( P<0.05 ).Fluoxetine treated EAE mice showed decreased degree of inflammatory infiltration;the mean rank of positive cells lower in the fluoxetine group than those in the EAE group,the differences were significant between two groups ( P<0.05 ).The expression of CXCL10 in the peripheral blood plasma of fluoxetine group were lower than those in the EAE group ,there were significant differences between two groups ( P<0.05 ).Levels of LCN2 expression were correlated with those of CXCL 10 in the EAE group.Conclusion: LCN2, CXCL10 are correlated with the pathogenesis of EAE.Fluoxetine could alleviate clinical symptoms of EAE and alleviate the morbidity of EAE.

5.
Immune Network ; : 342-347, 2011.
Artigo em Inglês | WPRIM | ID: wpr-60141

RESUMO

BACKGROUND: Glial cells are involved in immune and inflammatory responses in the central nervous system (CNS). Glial cells such as microglia and astrocytes also provide structural and functional support for neurons. Migration and morphological changes of CNS cells are associated with their physiological as well as pathological functions. The secreted protein lipocalin-2 (LCN2) has been previously implicated in regulation of diverse cellular processes of glia and neurons, including cell migration and morphology. METHODS: Here, we employed a zebrafish model to analyze the role of LCN2 in CNS cell migration and morphology in vivo. In the first part of this study, we examined the indirect effect of LCN2 on cell migration and morphology of microglia, astrocytes, and neurons cultured in vitro. RESULTS: Conditioned media collected from LCN2-treated astrocytes augmented migration of glia and neurons in the Boyden chamber assay. The conditioned media also increased the number of neuronal processes. Next, in order to further understand the role of LCN2 in the CNS in vivo, LCN2 was ectopically expressed in the zebrafish spinal cord. Expression of exogenous LCN2 modulated neuronal cell migration in the spinal cord of zebrafish embryos, supporting the role of LCN2 as a cell migration regulator in the CNS. CONCLUSION: Thus, LCN2 proteins secreted under diverse conditions may play an important role in CNS immune and inflammatory responses by controlling cell migration and morphology.


Assuntos
Astrócitos , Movimento Celular , Sistema Nervoso Central , Meios de Cultivo Condicionados , Estruturas Embrionárias , Microglia , Neuroglia , Neurônios , Proteínas , Medula Espinal , Peixe-Zebra
6.
Journal of Korean Medical Science ; : 302-306, 2008.
Artigo em Inglês | WPRIM | ID: wpr-173549

RESUMO

In a previous search for the differentially expressed genes in keratinocyte differentiation, we identified neutrophil gelatinase-associated lipocalin (NGAL) as a calcium- induced gene. In this study, we further verified the expression of NGAL in cultured keratinocytes as well as in several skin diseases. Reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and ELISA clearly showed that NGAL expression was markedly increased in calcium-induced keratinocyte differentiation in vitro. However, in our previous report, NGAL expression was not detected in normal skin tissue except for hair follicle by in situ hybridization and immunohistochemistry, indicating the difference of cell status between in vitro and in vitro conditions. Interestingly, NGAL expression was highly increased in psoriasis-like inflammatory disorders (lichen planus and pityriasis rubura pilaris) and skin cancers (keratoacanthoma and squamous cell carcinoma), implying that NGAL may be related with the epidermal hyperplasia. Collectively, these results reveal the potential importance of NGAL in the maintenance of skin homeostasis.


Assuntos
Humanos , Proteínas de Fase Aguda/biossíntese , Cálcio/metabolismo , Diferenciação Celular , Meios de Cultura , Meios de Cultivo Condicionados , Ensaio de Imunoadsorção Enzimática , Regulação da Expressão Gênica , Homeostase , Queratinócitos/enzimologia , Lipocalinas/biossíntese , Modelos Biológicos , Proteínas Proto-Oncogênicas/biossíntese , Psoríase/enzimologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Pele/metabolismo , Neoplasias Cutâneas/enzimologia
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