scholarly journals The Scaffold Protein Cybr Is Required for Cytokine-Modulated Trafficking of Leukocytes In Vivo

2006 ◽  
Vol 26 (14) ◽  
pp. 5249-5258 ◽  
Author(s):  
Vincenzo Coppola ◽  
Colleen A. Barrick ◽  
Sara Bobisse ◽  
Maria Cecilia Rodriguez-Galan ◽  
Michela Pivetta ◽  
...  
Keyword(s):  
Immune System ◽  
Cytotoxic T Lymphocyte ◽  
Leukemia Virus ◽  
Physiological Role ◽  
Scaffold Protein ◽  
Nucleotide Exchange ◽  
Lymphocyte Migration ◽  
And Migration

ABSTRACT Trafficking and cell adhesion are key properties of cells of the immune system. However, the molecular pathways that control these cellular behaviors are still poorly understood. Cybr is a scaffold protein highly expressed in the hematopoietic/immune system whose physiological role is still unknown. In vitro studies have shown it regulates LFA-1, a crucial molecule in lymphocyte attachment and migration. Cybr also binds cytohesin-1, a guanine nucleotide exchange factor for the ARF GTPases, which affects actin cytoskeleton remodeling during cell migration. Here we show that expression of Cybr in vivo is differentially modulated by type 1 cytokines during lymphocyte maturation. In mice, Cybr deficiency negatively affects leukocytes circulating in blood and lymphocytes present in the lymph nodes. Moreover, in a Th1-polarized mouse model, lymphocyte trafficking is impaired by loss of Cybr, and Cybr-deficient mice with aseptic peritonitis have fewer cells than controls present in the peritoneal cavity, as well as fewer leukocytes leaving the bloodstream. Mutant mice injected with Moloney murine sarcoma/leukemia virus develop significantly larger tumors than wild-type mice and have reduced lymph node enlargement, suggesting reduced cytotoxic T-lymphocyte migration. Taken together, these data support a role for Cybr in leukocyte trafficking, especially in response to proinflammatory cytokines in stress conditions.

SM22α inhibits lamellipodium formation and migration via Ras-Arp2/3 signaling in synthetic VSMCs

2016 ◽  
Vol 311 (5) ◽  
pp. C758-C767 ◽  
Author(s):  
Pin Lv ◽  
Fan Zhang ◽  
Ya-Juan Yin ◽  
Yu-Can Wang ◽  
Min Gao ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Lesion ◽  
Flavonoid Compound ◽  
Cell Cortex ◽  
Dependent Manner ◽  
Nucleotide Exchange ◽  
Migration Activity ◽  
And Migration

We previously demonstrated that smooth muscle (SM) 22α promotes the migration activity in contractile vascular smooth muscle cells (VSMCs). Based on the varied functions exhibited by SM22α in different VSMC phenotypes, we investigated the effect of SM22α on VSMC migration under pathological conditions. The results demonstrated that SM22α overexpression in synthetic VSMCs inhibited platelet-derived growth factor (PDGF)-BB-induced cell lamellipodium formation and migration, which was different from its action in contractile cells. The results indicated two distinct mechanisms underlying inhibition of lamellipodium formation by SM22α, increased actin dynamic stability and decreased Ras activity via interference with interactions between Ras and guanine nucleotide exchange factor. The former inhibited actin cytoskeleton rearrangement in the cell cortex, while the latter significantly disrupted actin nucleation activation of the Arp2/3 complex. Baicalin, a herb-derived flavonoid compound, inhibited VSMC migration via upregulation of SM22α expression in vitro and in vivo. These data suggest that SM22α regulates lamellipodium formation and cell migration in a phenotype-dependent manner in VSMCs, which may be a new therapeutic target for vascular lesion formation.

scholarly journals Mouse APOBEC3 Restricts Friend Leukemia Virus Infection and Pathogenesis In Vivo

2008 ◽  
Vol 82 (22) ◽  
pp. 10998-11008 ◽  
Author(s):  
Eri Takeda ◽  
Sachiyo Tsuji-Kawahara ◽  
Mayumi Sakamoto ◽  
Marc-André Langlois ◽  
Michael S. Neuberger ◽  
...  
Keyword(s):  
Leukemia Virus ◽  
Physiological Role ◽  
Erythroid Cell ◽  
Chromosome 15 ◽  
Host Immune Responses ◽  
Virus Complex ◽  
Tumor Virus ◽  
Retroviral Replication

ABSTRACT Several members of the apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like complex 3 (APOBEC3) family in primates act as potent inhibitors of retroviral replication. However, lentiviruses have evolved mechanisms to specifically evade host APOBEC3. Likewise, murine leukemia viruses (MuLV) exclude mouse APOBEC3 from the virions and cleave virion-incorporated APOBEC3. Although the betaretrovirus mouse mammary tumor virus has been shown to be susceptible to mouse APOBEC3, it is not known if APOBEC3 has a physiological role in restricting more widely distributed and long-coevolved mouse gammaretroviruses. The pathogenicity of Friend MuLV (F-MuLV) is influenced by several host genes: some directly restrict the cell entry or integration of the virus, while others influence the host immune responses. Among the latter, the Rfv3 gene has been mapped to chromosome 15 in the vicinity of the APOBEC3 locus. Here we have shown that polymorphisms at the mouse APOBEC3 locus indeed influence F-MuLV replication and pathogenesis: the APOBEC3 alleles of F-MuLV-resistant C57BL/6 and -susceptible BALB/c mice differ in their sequences and expression levels in the hematopoietic tissues and in their abilities to restrict F-MuLV replication both in vitro and in vivo. Furthermore, upon infection with the pathogenic Friend virus complex, (BALB/c × C57BL/6)F1 mice displayed an exacerbated erythroid cell proliferation when the mice carried a targeted disruption of the C57BL/6-derived APOBEC3 allele. These results indicate, for the first time, that mouse APOBEC3 is a physiologically functioning restriction factor to mouse gammaretroviruses.

scholarly journals Regulation of In Vitro and In Vivo Immune Functions by the Cytosolic Adaptor Protein SKAP-HOM

2005 ◽  
Vol 25 (18) ◽  
pp. 8052-8063 ◽  
Author(s):  
M. Togni ◽  
K. D. Swanson ◽  
S. Reimann ◽  
S. Kliche ◽  
A. C. Pearce ◽  
...  
Keyword(s):  
Immune System ◽  
T Cell ◽  
Physiological Role ◽  
Adaptor Protein ◽  
T Cell Responses ◽  
Specific Substrate ◽  
Immune Functions ◽  
Cell Responses

ABSTRACT SKAP-HOM is a cytosolic adaptor protein representing a specific substrate for the Src family protein tyrosine kinase Fyn. Previously, several groups have provided experimental evidence that SKAP-HOM (most likely in cooperation with the cytosolic adaptor protein ADAP) is involved in regulating leukocyte adhesion. To further assess the physiological role of SKAP-HOM, we investigated the immune system of SKAP-HOM-deficient mice. Our data show that T-cell responses towards a variety of stimuli are unaffected in the absence of SKAP-HOM. Similarly, B-cell receptor (BCR)-mediated total tyrosine phosphorylation and phosphorylation of Erk, p38, and JNK, as well as immunoreceptor-mediated Ca2+ responses, are normal in SKAP-HOM−/− animals. However, despite apparently normal membrane-proximal signaling events, BCR-mediated proliferation is strongly attenuated in the absence of SKAP-HOM−/−. In addition, adhesion of activated B cells to fibronectin (a ligand for β1 integrins) as well as to ICAM-1 (a ligand for β2 integrins) is strongly reduced. In vivo, the loss of SKAP-HOM results in a less severe clinical course of experimental autoimmune encephalomyelitis following immunization of mice with the encephalitogenic peptide of MOG (myelin oligodendrocyte glycoprotein). This is accompanied by strongly reduced serum levels of MOG-specific antibodies and lower MOG-specific T-cell responses. In summary, our data suggest that SKAP-HOM is required for proper activation of the immune system, likely by regulating the cross-talk between immunoreceptors and integrins.

scholarly journals LncRNA KRT19P3 Is Involved in Breast Cancer Cell Proliferation, Migration and Invasion

2022 ◽  
Vol 11 ◽  
Author(s):  
Yanping Fan ◽  
Xiaotong Dong ◽  
Meizeng Li ◽  
Pengju Liu ◽  
Jie Zheng ◽  
...  
Keyword(s):  
Immune System ◽  
Cytotoxic T Lymphocyte ◽  
Migration And Invasion ◽  
Cancer Tissue ◽  
Ki 67 ◽  
Invasion Rate ◽  
Programmed Death ◽  
Positive Rate

Long non-coding RNAs (LncRNAs) have already been taken as critical regulatory molecules in breast carcinoma (BC). Besides, the progression of BC is closely associated with the immune system. However, the relationship between lncRNAs and the tumor immune system in BC has not been fully studied. LncRNA KRT19P3 has been reported to inhibit the progression of gastric cancer. In the present study, we first discovered that KRT19P3 was downregulated in BC tissues compared with para cancer tissue. Then we showed that KRT19P3 could be used as a marker to differentiate BC from para cancer tissue. Increased expression of KRT19P3 markedly inhibited the proliferation, migration, and invasion rate of BC cells in vitro and tumor growth of BC in vivo. Conversely, KRT19P3 knockdown by siRNA markedly promoted the proliferation, migration, and invasion rate of BC cells after being transfected. Comparison of clinical parameters showed an inverse relationship between the expression of KRT19P3 and pathological grade. Furthermore, immunohistochemistry (IHC) was applied to reveal the positive rate of the expression of Ki-67, programmed death-ligand 1 (PD-L1), and CD8 in BC tissues. Correlation analysis showed that Ki-67 and PD-L1 were inversely proportional to KRT19P3 but CD8 was directly proportional to KRT19P3. In conclusion, this study demonstrated that lncRNA KRT19P3 inhibits BC progression, and may affect the expression of PD-L1 in BC, which in turn affects CD8+ T (CD8 positive Cytotoxic T lymphocyte) cells in the immune microenvironment.

Targeting Matrix Metalloproteinases in Atherosclerosis and Cardiovascular Dysfunction

2019 ◽  
Vol 70 (2) ◽  
pp. 718-720
Author(s):  
Lucia Corina Dima-Cozma ◽  
Sebastian Cozma ◽  
Delia Hinganu ◽  
Cristina Mihaela Ghiciuc ◽  
Florin Mitu
Keyword(s):  
Smooth Muscle ◽  
Matrix Metalloproteinases ◽  
Cholesterol Synthesis ◽  
Balloon Dilation ◽  
Aortic Aneurysms ◽  
Arterial Lesions ◽  
Smooth Muscle Cell Migration ◽  
And Migration

Matrix metalloproteinases (MMPs) are the primary mediators of extracellular remodeling and their properties are useful in diagnostic evaluation and treatment. They are zinc-dependent proteases. MMPs have been involved in the mechanisms of atherosclerosis in various arterial areas, ischemic heart disease and myocardial infarction, atrial fibrillation and aortic aneurysms. Recently, MMP9 has been implicated in dyslipidemia and cholesterol synthesis by the liver. Increased MMP expression and activity has been associated with neointimal arterial lesions and migration of smooth muscle cells after arterial balloon dilation, while MMP inhibition decreases smooth muscle cell migration in vivo and in vitro.

scholarly journals Hypoxic glioma-derived exosomes promote M2-like macrophage polarization by enhancing autophagy induction

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Jianye Xu ◽  
Jian Zhang ◽  
Zongpu Zhang ◽  
Zijie Gao ◽  
Yanhua Qi ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Autophagy Induction ◽  
Antitumor Immunotherapy ◽  
Novel Biomarkers ◽  
And Migration ◽  
Immunosuppressive Microenvironment ◽  
Proliferation And Migration ◽  
Glioma Progression

AbstractExosomes participate in intercellular communication and glioma microenvironment modulation, but the exact mechanisms by which glioma-derived exosomes (GDEs) promote the generation of the immunosuppressive microenvironment are still unclear. Here, we investigated the effects of GDEs on autophagy, the polarization of tumor-associated macrophages (TAMs), and glioma progression. Compared with normoxic glioma-derived exosomes (N-GDEs), hypoxic glioma-derived exosomes (H-GDEs) markedly facilitated autophagy and M2-like macrophage polarization, which subsequently promoted glioma proliferation and migration in vitro and in vivo. Western blot and qRT-PCR analyses indicated that interleukin 6 (IL-6) and miR-155-3p were highly expressed in H-GDEs. Further experiments showed that IL-6 and miR-155-3p induced M2-like macrophage polarization via the IL-6-pSTAT3-miR-155-3p-autophagy-pSTAT3 positive feedback loop, which promotes glioma progression. Our study clarifies a mechanism by which hypoxia and glioma influence autophagy and M2-like macrophage polarization via exosomes, which could advance the formation of the immunosuppressive microenvironment. Our findings suggest that IL-6 and miR-155-3p may be novel biomarkers for diagnosing glioma and that treatments targeting autophagy and the STAT3 pathway may contribute to antitumor immunotherapy.

scholarly journals The roles and prognostic significance of ABI1-TSV-11 expression in patients with left-sided colorectal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Zhang ◽  
Zhaohui Zhong ◽  
Mei Li ◽  
Jingyi Chen ◽  
Tingru Lin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
The Cancer Genome Atlas ◽  
Actin Dynamics ◽  
Elevated Expression ◽  
Sw480 Cells ◽  
And Migration

AbstractAbnormally expressed and/or phosphorylated Abelson interactor 1 (ABI1) participates in the metastasis and progression of colorectal cancer (CRC). ABI1 presents as at least 12 transcript variants (TSVs) by mRNA alternative splicing, but it is unknown which of them is involved in CRC metastasis and prognosis. Here, we firstly identified ABI1-TSV-11 as a key TSV affecting the metastasis and prognosis of left-sided colorectal cancer (LsCC) and its elevated expression is related to lymph node metastasis and shorter overall survival (OS) in LsCC by analyzing data from The Cancer Genome Atlas and TSVdb. Secondly, ABI1-TSV-11 overexpression promoted LoVo and SW480 cells adhesion and migration in vitro, and accelerated LoVo and SW480 cells lung metastasis in vivo. Finally, mechanism investigations revealed that ABI1-isoform-11 interacted with epidermal growth factor receptor pathway substrate 8 (ESP8) and regulated actin dynamics to affect LoVo and SW480 cells biological behaviors. Taken together, our data demonstrated that ABI1-TSV-11 plays an oncogenic role in LsCC, it is an independent risk factor of prognosis and may be a potential molecular marker and therapeutic target in LsCC.

scholarly journals Cyr61 promotes Schwann cell proliferation and migration via αvβ3 integrin

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zhenghui Cheng ◽  
Yawen Zhang ◽  
Yinchao Tian ◽  
Yuhan Chen ◽  
Fei Ding ◽  
...  
Keyword(s):  
Nerve Injury ◽  
Peripheral Nerves ◽  
Molecular Mechanisms ◽  
Αvβ3 Integrin ◽  
Promoting Effect ◽  
Ccn Family ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Schwann cells (SCs) play a crucial role in the repair of peripheral nerves. This is due to their ability to proliferate, migrate, and provide trophic support to axon regrowth. During peripheral nerve injury, SCs de-differentiate and reprogram to gain the ability to repair nerves. Cysteine-rich 61 (Cyr61/CCN1) is a member of the CCN family of matrix cell proteins and have been reported to be abundant in the secretome of repair mediating SCs. In this study we investigate the function of Cyr61 in SCs. Results We observed Cyr61 was expressed both in vivo and in vitro. The promoting effect of Cyr61 on SC proliferation and migration was through autocrine and paracrine mechanisms. SCs expressed αvβ3 integrin and the effect of Cyr61 on SC proliferation and migration could be blocked via αvβ3 integrin. Cyr61 could influence c-Jun protein expression in cultured SCs. Conclusions In this study, we found that Cyr61 promotes SC proliferation and migration via αvβ3 integrin and regulates c-Jun expression. Our study contributes to the understanding of cellular and molecular mechanisms underlying SC’s function during nerve injury, and thus, may facilitate the regeneration of peripheral nerves after injury.

Sign in / Sign up

Export Citation Format

Share Document