Connections of annexin A1 and translocator protein-18 kDa on toll like receptor stimulated BV-2 cells

Pantaleão, Lorena do Nascimento; Rocha, Gustavo Henrique Oliveira da; Reutelingsperger, Chris; Tiago, Manoela; Maria‐Engler, Silvya Stuchi; Solito, Egle; Farsky, Sandra P.

doi:10.1016/j.yexcr.2018.04.008

Cited by 8 publications

(4 citation statements)

References 56 publications

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“…Indeed, our results showed that FPR2/3 knockout mice and pharmacological inhibition of FPR2 by using WRW4 led not to inhibition but an increase of the levels of IL‐1β. In fact, exogenous AnxA1 acting on FPR2 may downmodulate the Myd88/NFκB pathway and downregulate IL‐1β secretion, 50 although we found here that pre‐treatment of BMDMs with Ac2‐26 had no effect on IL‐1β release.…”

Section: Discussioncontrasting

confidence: 74%

The role of annexin A1 in the modulation of the NLRP3 inflammasome

Galvão¹,

Carvalho²,

Vago³

et al. 2020

Immunology

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Annexins are well-known Ca 2+ phospholipid-binding proteins, which have a wide variety of cellular functions. The role of annexin A1 (AnxA1) in the innate immune system has focused mainly on the anti-inflammatory and proresolving properties through its binding to the formyl-peptide receptor 2 (FPR2)/ALX receptor. However, studies suggesting an intracellular role of AnxA1 are emerging. In this study, we aimed to understand the role of AnxA1 for interleukin (IL)-1b release in response to activators of the nucleotide-binding domain leucine-rich repeat (NLR) and pyrin domain containing receptor 3 (NLRP3) inflammasome. Using AnxA1 knockout mice, we observed that AnxA1 is required for IL-1b release in vivo and in vitro. These effects were due to reduction of transcriptional levels of IL-1b, NLRP3 and caspase-1, a step called NLRP3 priming. Moreover, we demonstrate that AnxA1 co-localize and directly bind to NLRP3, suggesting the role of AnxA1 in inflammasome activation is independent of its anti-inflammatory role via FPR2. Therefore, AnxA1 regulates NLRP3 inflammasome priming and activation in a FPR2-independent manner.Bone marrow-derived macrophages (BMDMs) were obtained as previously described. 31 Briefly, bone marrow cells were collected from femurs of wild-type (WT), AnxA1 À/À and FPR2/3 À/À mice and differentiated for 7 days in RPMI 1640 supplemented with 20% of fetal bovine serum (FBS) and 30% L929 conditioned medium.

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Section: Discussioncontrasting

confidence: 74%

The role of annexin A1 in the modulation of the NLRP3 inflammasome

Galvão¹,

Carvalho²,

Vago³

et al. 2020

Immunology

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“…This is the first direct evidence of annexin A1 overexpression in lymph node metastasis of head and neck cancer. Annexin A1 is a protein involved in inflammation [ 89 ], apoptosis [ 90 ], cell differentiation [ 91 ], migration, invasion [ 92 ], and signaling [ 93 ]. It is a substrate of growth factors and kinases and exhibits abnormal (high or low) levels in several tumors and inflammatory conditions (reviewd by [ 94 – 96 ].…”

Section: Discussionmentioning

confidence: 99%

Differentially expressed proteins in positive versus negative HNSCC lymph nodes

et al. 2018

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BackgroundLymph node metastasis is one of the most important prognostic factors in head and neck squamous cell carcinomas (HNSCCs) and critical for delineating their treatment. However, clinical and histological criteria for the diagnosis of nodal status remain limited. In the present study, we aimed to characterize the proteomic profile of lymph node metastasis from HNSCC patients.MethodsIn the present study, we used one- and two-dimensional electrophoresis and mass spectrometry analysis to characterize the proteomic profile of lymph node metastasis from HNSCC.ResultsComparison of metastatic and non-metastatic lymph nodes showed 52 differentially expressed proteins associated with neoplastic development and progression. The results reinforced the idea that tumors from different anatomical subsites have dissimilar behaviors, which may be influenced by micro-environmental factor including the lymphatic network. The expression pattern of heat shock proteins and glycolytic enzymes also suggested an effect of the lymph node environment in controlling tumor growth or in metabolic reprogramming of the metastatic cell. Our study, for the first time, provided direct evidence of annexin A1 overexpression in lymph node metastasis of head and neck cancer, adding information that may be useful for diagnosing aggressive disease.ConclusionsIn brief, this study contributed to our understanding of the metastatic phenotype of HNSCC and provided potential targets for diagnostic in this group of carcinomas.Electronic supplementary materialThe online version of this article (10.1186/s12920-018-0382-6) contains supplementary material, which is available to authorized users.

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“…Bone marrow cells, obtained as described above, were incubated in 12-well plates (10 6 cells per well) in the presence or absence of WRW4 (10 μM; Tocris Bioscience, UK), a selective antagonist of FPR2 51,52 , for 1 h. Then, cells were treated with rAnxA1 (100 nM) for 12 h at 37 °C in 5% CO 2 and immunophenotyped as above.…”

Section: Methodsmentioning

confidence: 99%

Extracellular annexin-A1 promotes myeloid/granulocytic differentiation of hematopoietic stem/progenitor cells via the Ca2+/MAPK signalling transduction pathway

et al. 2019

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Annexin A1 (AnxA1) modulates neutrophil life span and bone marrow/blood cell trafficking thorough activation of formyl-peptide receptors (FPRs). Here, we investigated the effect of exogenous AnxA1 on haematopoiesis in the mouse. Treatment of C57BL/6 mice with recombinant AnxA1 (rAnxA1) reduced the granulocyte–macrophage progenitor (GMP) population in the bone marrow, enhanced the number of mature granulocytes Gr-1+Mac-1+ in the bone marrow as well as peripheral granulocytic neutrophils and increased expression of mitotic cyclin B1 on hematopoietic stem cells (HSCs)/progenitor cells (Lin−Sca-1+c-Kit+: LSK). These effects were abolished by simultaneous treatment with Boc-2, an FPR pan-antagonist. In in vitro studies, rAnxA1 reduced both HSC (LSKCD90lowFLK-2−) and GMP populations while enhancing mature cells (Gr1+Mac1+). Moreover, rAnxA1 induced LSK cell proliferation (Ki67+), increasing the percentage of cells in the S/G2/M cell cycle phases and reducing Notch-1 expression. Simultaneous treatment with WRW4, a selective FPR2 antagonist, reversed the in vitro effects elicited by rAnxA1. Treatment of LSK cells with rAnxA1 led to phosphorylation of PCLγ2, PKC, RAS, MEK, and ERK1/2 with increased expression of NFAT2. In long-term bone marrow cultures, rAnxA1 did not alter the percentage of LSK cells but enhanced the Gr-1+Mac-1+ population; treatment with a PLC (U73122), but not with a PKC (GF109203), inhibitor reduced rAnxA1-induced phosphorylation of ERK1/2 and Elk1. Therefore, we identify here rAnxA1 as an inducer of HSC/progenitor cell differentiation, favouring differentiation of the myeloid/granulocytic lineage, via Ca2+/MAPK signalling transduction pathways.

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Connections of annexin A1 and translocator protein-18 kDa on toll like receptor stimulated BV-2 cells

Abstract: exogenous ANXA1 down-modulates LPS-induced TSPO via MyD-88/NF-κB pathways, and constitutive TSPO is pivotal for the control of ANXA1 on TNFα secretion. TSPO actions may be involved with the mechanisms of ANXA1 on inflammatory brain diseases.

Cited by 8 publications

References 56 publications

The role of annexin A1 in the modulation of the NLRP3 inflammasome

The role of annexin A1 in the modulation of the NLRP3 inflammasome

Differentially expressed proteins in positive versus negative HNSCC lymph nodes

Extracellular annexin-A1 promotes myeloid/granulocytic differentiation of hematopoietic stem/progenitor cells via the Ca2+/MAPK signalling transduction pathway

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Connections of annexin A1 and translocator protein-18 kDa on toll like receptor stimulated BV-2 cells

Abstract: exogenous ANXA1 down-modulates LPS-induced TSPO via MyD-88/NF-κB pathways, and constitutive TSPO is pivotal for the control of ANXA1 on TNFα secretion. TSPO actions may be involved with the mechanisms of ANXA1 on inflammatory brain diseases.

Cited by 8 publications

References 56 publications

The role of annexin A1 in the modulation of the NLRP3 inflammasome

The role of annexin A1 in the modulation of the NLRP3 inflammasome

Differentially expressed proteins in positive versus negative HNSCC lymph nodes

Extracellular annexin-A1 promotes myeloid/granulocytic differentiation of hematopoietic stem/progenitor cells via the Ca2+/MAPK signalling transduction pathway

Contact Info

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Connections of annexin A1 and translocator protein-18 kDa on toll like receptor stimulated BV-2 cells