Abstract:
:Multiple sclerosis (MS) is a chronic immuno-inflammatory disease of the central nervous system characterized by demyelination and axonal damage. Cognitive changes are common in individuals with MS since inflammatory molecules secreted by microglia interfere with the physiological mechanisms of synaptic plasticity. According to previous data, inhibition of PDE5 promotes the accumulation of cGMP, which inhibits neuroinflammation and seems to improve synaptic plasticity and memory. The present study aimed to evaluate the effect of sildenafil on the signaling pathways of neuroinflammation and synaptic plasticity in experimental autoimmune encephalomyelitis (EAE). C57BL/6 mice were divided into three experimental groups (n = 10/group): (a) Control; (b) EAE; (c) EAE + sild (25 mg/kg/21 days). Sildenafil was able to delay the onset and attenuate the severity of the clinical symptoms of EAE. The drug also reduced the infiltration of CD4+ T lymphocytes and their respective IL-17 and TNF-α cytokines. Moreover, sildenafil reduced neuroinflammation in the hippocampus (assessed by the reduction of inflammatory markers IL-1β, pIKBα and pNFkB and reactive gliosis, as well as elevating the inhibitory cytokines TGF-β and IL-10). Moreover, sildenafil induced increased levels of NeuN, BDNF and pCREB, protein kinases (PKA, PKG, and pERK) and synaptophysin, and modulated the expression of the glutamate receptors AMPA and NMDA. The present findings demonstrated that sildenafil has therapeutic potential for cognitive deficit associated with multiple sclerosis.
journal_name
Int Immunopharmacoljournal_title
International immunopharmacologyauthors
Araújo SMDR,Duarte-Silva E,Marinho CGS,Oliveira WH,França MER,Lós D,Peron G,Tomaz L,Bonfanti AP,Verinaud L,Peixoto CAdoi
10.1016/j.intimp.2020.106581subject
Has Abstractpub_date
2020-08-01 00:00:00pages
106581eissn
1567-5769issn
1878-1705pii
S1567-5769(20)30868-7journal_volume
85pub_type
杂志文章abstract::Cyclosporine A (CsA) is the first immunosuppressant universally used in allotransplantation. However, it has been demonstrated that this drug produces side effects in several organs, particularly in the kidney and in the heart. Since the immunosuppressive therapy induces myocardial toxicity, the aim of this study was ...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/S1567-5769(03)00020-1
更新日期:2003-03-01 00:00:00
abstract::Previous work has shown that in vitro thymulin treatments have the ability to enhance natural killer (NK) cell cytotoxicity. The purpose of the experiments presented here was to examine the in vivo effects of thymulin on avian NK cell activity in response to a viral infection. Five and a half-week-old K-strain chicken...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/s1567-5769(02)00236-9
更新日期:2003-01-01 00:00:00
abstract::Bee venom (BV) has been known to inhibit proliferation and induce apoptosis in cancer cells. However, the molecular mechanisms involved in BV-induced apoptosis are still uncharacterized in human leukemic cells. In the present study, we report that BV induces apoptosis in leukemic U937 cells through downregulation of E...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2006.07.027
更新日期:2006-12-05 00:00:00
abstract::Acute lung injury (ALI) is a severe disease characterized by several inflammatory responses in the lung with high mortality. We applied a mouse model of the pulmonary inflammation induced by the intratracheal instillation of bleomycin which is widely used to induce ALI and fibrosis in animal models. We hypothesized th...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2020.106542
更新日期:2020-07-01 00:00:00
abstract::Inflammation plays an important role in the process of atherosclerosis (AS). Inhibition of inflammation is an effective way to prevent AS. Imperatorin (IMP) is a kind of furan coumarin with various activities. In this study, the anti-inflammatory effect of IMP was explored in oxidized low-density lipoprotein (ox-LDL)-...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2020.107170
更新日期:2021-01-01 00:00:00
abstract::Effects of a topical corticosteroid drug, diflucortolone valerate, on the mRNA expressions for four CC- and four CXC-chemokines, which have been reported to be associated with recruitment of different kinds of proinflammatory and inflammatory cells, were investigated by RT-PCR in mice with 2,4,6-trinitrochlorobenzene ...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2003.10.005
更新日期:2004-01-01 00:00:00
abstract::Our group recently reported the strong anti-inflammatory effects of geniposide (Gen), a bioactive iridoid glucoside derived from gardenia jasminoides, in a mouse acute lung injury model. Herein, we hypothesized that Gen might also have potential therapeutic benefits in treatment of asthma, which was tested in a mouse ...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2013.06.028
更新日期:2013-11-01 00:00:00
abstract::Regulatory T cells (Treg), formerly known as suppressor T cells, are essential for maintaining self-tolerance as well as immune homeostasis. Lack of Treg or normal function of Treg often leads to lymphoproliferative syndrome and autoimmunity in human and mouse. The chromatin remodeling BAF complex regulates gene expre...
journal_title:International immunopharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.intimp.2009.01.019
更新日期:2009-05-01 00:00:00
abstract::Leukocytes accumulate at sites of inflammation and immunological reaction in response to locally existing chemotactic mediators. N-formyl peptides, such as fMet-Leu-Phe (fMLF), are some of the first identified and most potent chemoattractants for phagocytic leukocytes. In addition to the bacterial peptide fMLF and the...
journal_title:International immunopharmacology
pub_type: 杂志文章,评审
doi:10.1016/s1567-5769(01)00150-3
更新日期:2002-01-01 00:00:00
abstract::Natural killer (NK) cells eliminate cancer cells in a contact-dependent manner. However, how NK cells find cancer cells remain unclear. Here, using time-lapse imaging, we investigated how individual NK cells migrate toward cancer cells. Although naïve B16F10 cancer cells produce low levels of chemokines, IFN-γ-treated...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2018.07.026
更新日期:2018-10-01 00:00:00
abstract::Accumulating evidence indicates that microRNA-146a (miR-146a), a well-known anti-inflammatory miRNA, acts as a negative feedback regulator of the innate immune response, but its role in modulation of inflammatory bowel disease (IBD) remains unclear and the issue related to the stability of exogenous miR-146a in blood ...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2018.12.043
更新日期:2019-03-01 00:00:00
abstract::Inflammatory bowel disease (IBD) is a significant public health problem in the United States. Abdominal pain is a major complaint among individuals with IBD. Successful IBD management not only controls enteric inflammation, but also reduces abdominal discomfort. Recently, increased attention has been focused on altern...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2018.09.005
更新日期:2018-11-01 00:00:00
abstract::We previously demonstrated that decreased expression of miR-140-5p was associated with the progression of multiple sclerosis (MS) and miR-140-5p targeted STAT1 and interfered with the expression of IFN-γ. However, the underlying mechanisms how miR-140-5p regulated the differentiation of encephalomyelitic CD4+T cell re...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2019.105778
更新日期:2019-10-01 00:00:00
abstract::Bacillus anthracis is a lethal agent of anthrax disease and the toxins are required in anthrax pathogenesis. The anthrax lethal toxin can trigger NLRP1b inflammasome activation and pyroptosis. Although the underlying mechanism is well understood, the medications targeting the NLRP1b inflammasome are not available in t...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2020.106664
更新日期:2020-08-01 00:00:00
abstract::Prenylated flavonoids are a unique class of naturally occurring flavonoids that have various pharmacological activities. In the present study, we investigated the anti-inflammatory effect in murine macrophages of a prenylated flavonoid, 10-oxomornigrol F (OMF), which was isolated from the twigs of Morus alba (Moraceae...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2017.12.015
更新日期:2018-02-01 00:00:00
abstract::Immunotherapy is the only effective treatment for scorpion stings. However the efficiency of this treatment varies depending on the forms of the antibodies and route of administration used. The antibodies are mostly injected as F(ab )(2) fragments. In this study, we investigated damage to the heart and lung tissue and...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2008.05.011
更新日期:2008-10-01 00:00:00
abstract::Endothelial cells play an important role in inflammatory diseases like rheumatoid arthritis by recruitment of inflammatory cells. The cytokines TNF-alpha and IL-1beta are major inducers of endothelial cell activation and are stimulators of inflammatory signal transduction pathway involving p38 MAPK (mitogen-activated ...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2005.03.005
更新日期:2005-07-01 00:00:00
abstract::In this study, Mtb8.4 and HspX, which are expressed at proliferating and dormant stages of Mycobacterium tuberculosis (M. tuberculosis), respectively, were chosen to construct two fusion proteins, Mtb8.4-HspX (8.4H) and HspX-Mtb8.4 (H8.4), and we investigated whether the antigen dose and protein sequential order could...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2017.10.015
更新日期:2017-12-01 00:00:00
abstract::Human melanoma Colo 679 cells were made resistant to doxorubicin (adriamycin, ADM) by continuous exposure to ascending concentrations of the drug and Colo/ADM80; a variant which grew continuously in the presence of 80 ng/ml of ADM was thus established. Human peripheral blood mononuclear cells (PBMC) produced interfero...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/s1567-5769(00)00026-6
更新日期:2001-02-01 00:00:00
abstract::Asthma is an inflammatory disorder of the airways dominated by a Th2-type pattern. Recently, an emerging interest arises whether transient receptor potential ankyrin 1 (TRPA1) plays a potential role in the adaptive immune response. In this study, the role of TRPA1 in the development and exacerbation of asthma was expl...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2020.106696
更新日期:2020-09-01 00:00:00
abstract::Mast cells play a critical role during the development of an allergic response. Upon activation by an antigen and IgE, via FcεRI receptors, mast cells release histamine and other mediators that initiate and propagate immediate hypersensitivity reactions. Mast cells also secrete cytokines that regulate the immune respo...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2013.01.017
更新日期:2013-03-01 00:00:00
abstract::Rheumatoid arthritis (RA) is an inflammatory disease with symmetric polyarthritis. IL-6 and NLRP3 inflammasome in macrophages contribute to the pathogenesis of RA. This study aimed to investigate the relationship between IL-6 and the NLRP3 inflammasome in RA. Here, we found that IL-6 inhibition reduced NLRP3 inflammas...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2020.106985
更新日期:2020-11-01 00:00:00
abstract::CXCR4 is a member of chemokine receptors and plays a vital role in numerous diseases and cancer processes, which makes the CXCR4/CXCL12 chemotactic axis a potential therapeutic target. In this study, we used lentiviral vectors as a novel technology to produce a monoclonal antibody against CXCR4. Lentivirus vector pLV-...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2016.04.020
更新日期:2016-07-01 00:00:00
abstract::The formation of an immunosuppressive microenvironment and up-regulation of PD-L1 protein are the main causes of tumor immune escape. Previous reports suggest that Angiotensin II (Ang II) can modulate the immune status of tumor microenvironment in non-small cell lung cancer (NSCLC), but the underlying mechanism remain...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2020.106507
更新日期:2020-07-01 00:00:00
abstract::Depression has been commonly associated with type 1 diabetes (T1D) and insulin covalently modified with catecholestrogens (CEs) was found in serum of these T1D patients. This study aimed to know whether depression link to higher antibodies against estrogenized insulin in T1D. ELISA (direct binding and competition) and...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2020.106712
更新日期:2020-09-01 00:00:00
abstract::The aim of this study was to evaluate the involvement of both B1 and B2 kinins receptors (B1R and B2R) in the fibroblast proliferation induced by the cytokine tumour necrosis factor (TNF) attempting to establish an in vitro model of wound healing. Murine fibroblasts L-929 were cultivated in 24 wells plaque until total...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2018.09.036
更新日期:2018-12-01 00:00:00
abstract::We had reported that in the ischemic heart, locally formed bradykinin (BK) and angiotensin II (Ang II) activate B2- and AT1-receptors on sympathetic nerve terminals (SNE), promoting reversal of the norepinephrine (NE) transporter in an outward direction (i.e., carrier-mediated NE release). Although both BK and Ang II ...
journal_title:International immunopharmacology
pub_type: 杂志文章,评审
doi:10.1016/s1567-5769(02)00148-0
更新日期:2002-12-01 00:00:00
abstract::The possible onset of Cytokine Release Syndrome (CRS) is an important consideration in the development of monoclonal antibody (mAb) therapeutics. In this study, several machine learning approaches are used to analyze CRS data. The analyzed data come from a human blood in vitro assay which was used to assess the potent...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2014.07.024
更新日期:2014-10-01 00:00:00
abstract::Rheumatoid arthritis (RA) synovial fibroblasts produce inflammatory mediators, which destruct cartilage and bone in RA joint. The aim of this study is to investigate the effect of myricetin on inflammatory cytokine/matrix metalloproteinase (MMP) production and mitogen-activated protein kinases (MAPKs) in IL-1beta-stim...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2010.04.010
更新日期:2010-07-01 00:00:00
abstract::Neutrophils are the first line of innate immune defense against infectious diseases. However, since their discovery by Elie Metchnikoff, they have always been considered tissue-destructive cells responsible for inflammatory tissue damage occurring during acute infections. Now, extensive research in the field of neutro...
journal_title:International immunopharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.intimp.2010.08.012
更新日期:2010-11-01 00:00:00