Annexin 1: An Endogenous Anti-Inflammatory Protein

The William Harvey Research Institute, London EC1M 6BQ, United Kingdom.
News in physiological sciences 05/2003; 18(2):60-4. DOI: 10.1152/nips.01424.2002
Source: PubMed

ABSTRACT A hallmark of inflammation is the mobilization of blood-borne leukocytes across microvessels to kill and remove the invading pathogen. For its damaging potential, leukocyte movement is finely regulated, and endogenous pathways exist to ensure the time dependency of this process. Annexin 1 and its receptor(s) are one example of these pathways.

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    • "Interestingly, cytoskeletal disruptive drugs have anti-inflammatory (Cronstein et al., 1995) and anti-proliferative roles (Dustin, 1963; Miquel et al., 1996; Tiozzo et al., 1996). Similarly ANXA1 also functions as an anti-inflammatory, anti-proliferative and apoptotic molecule (Flower and Rothwell, 1994; Perretti and Gavins, 2003), through post-translational modifications (Solito et al., 2006). "
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    ABSTRACT: Cytokeratins (CKs) constitute the cytoskeletal network and are regulated by post-translational modifications, acting not only as a mechanical support, but also in cell signaling and regulatory processes. Signaling is mediated by CK-associated proteins, such as Annexin A1 (ANXA1), a ligand of the CK18/CK8 complex. ANXA1 has a pivotal role in cellular and immunological responses, and together with CK18 have been implicated in several processes related to malignant transformation in breast cancer (BC). Our aim was to demonstrate how their interaction might be linked to BC development. We investigated transcript levels, protein expression and distribution for both targets in breast tissues of 92 patients (42 BCs and 50 benign diseases) using qPCR and immunohistochemistry, respectively. ANXA1 and CK18 mRNAs were inversely correlated, and their ratio in each TNM stage significantly differentiated BC from benign diseases (OR = 5.62). These differences did not mirror tissue protein levels, but a significant dichotomous protein distribution in tumor tissues was observed, differing from the expected co-localization observed during cell homeostasis. The disequilibrium of transcriptional levels between ANXA1/CK18 and alterations in their tissue distribution are present either in initial events or tumor progression, which suggest a critical event in BC. The broken dialog between ANXA1 and CK18 in normal breast tissues may play a critical role in BC development, and together may be used as combined targets for BC diagnostics.
    Acta Histochemica 09/2014; 116(7). DOI:10.1016/j.acthis.2014.06.008 · 1.71 Impact Factor
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    • "Annexin A1, a member of the annexin superfamily that contains 13 calcium or calcium and phospholipid-binding proteins, has been implicated in many diverse cellular functions, including anti-inflammatory effects [18,59,60], cell growth [61], apoptosis [62], membrane fusion, endocytosis, and exocytosis [63]. The consequences of annexin A1 dysregulation could therefore influence multiple pathways, some of which have been previously linked to autism pathophysiology. "
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    ABSTRACT: Validating the potential pathogenicity of copy number variants (CNVs) identified in genome-wide studies of autism spectrum disorders (ASD) requires detailed assessment of case/control frequencies, inheritance patterns, clinical correlations, and functional impact. Here, we characterize a small recurrent duplication in the annexin A1 (ANXA1) gene, identified by the Autism Genome Project (AGP) study. From the AGP CNV genomic screen in 2,147 ASD individuals, we selected for characterization an ANXA1 gene duplication that was absent in 4,964 population-based controls. We further screened the duplication in a follow-up sample including 1,496 patients and 410 controls, and evaluated clinical correlations and family segregation. Sequencing of exonic/downstream ANXA1 regions was performed in 490 ASD patients for identification of additional variants. The ANXA1 duplication, overlapping the last four exons and 3'UTR region, had an overall prevalence of 11/3,643 (0.30%) in unrelated ASD patients but was not identified in 5,374 controls. Duplication carriers presented no distinctive clinical phenotype. Family analysis showed neuropsychiatric deficits and ASD traits in multiple relatives carrying the duplication, suggestive of a complex genetic inheritance. Sequencing of exonic regions and the 3'UTR identified 11 novel changes, but no obvious variants with clinical significance. We provide multilevel evidence for a role of ANXA1 in ASD etiology. Given its important role as mediator of glucocorticoid function in a wide variety of brain processes, including neuroprotection, apoptosis, and control of the neuroendocrine system, the results add ANXA1 to the growing list of rare candidate genetic etiological factors for ASD.
    Molecular Autism 04/2014; 5(1):28. DOI:10.1186/2040-2392-5-28 · 5.41 Impact Factor
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    • "In contrast, overexpression of ANXA2 promotes cell proliferation in lung cancers [56] and inhibits apoptosis in breast cancers [57]. In addition, ANXA1 has been described as playing a homeostatic role in cells of the innate immune system [15, 58] and to act as a protective and anti-inflammatory protein in models of rheumatoid arthritis and myocardial infarct [15, 59, 60] by direct inhibition of phospholipase A2 [14]. Besides, ANXA2 can be detected in renal tissues from mice under normal status and renal injury [9, 10], and soluble ANXA2 tetramer has been reported to act as a soluble mediator of macrophage activation [19]. "
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    ABSTRACT: Background. We recently demonstrated high urine levels of annexin A1 (ANXA1) protein in a mouse Adriamycin-induced glomerulopathy (ADG) model. Objective. To establish ANXA1 as a potential biomarker for glomerular injury in patients. Methods. A time-course study in the mouse ADG model, followed by renal tissues and urine samples from patients with various types of glomerular disorders for ANXA1. Results. Urinary ANXA1 protein was (1) detectable in both the ADG model and in patients except those with minimal change disease (MCD); (2) positively correlated with renal lesions in patients; and (3) early detectable in diabetes patients with normoalbuminuria. Conclusions. ANXA1 is a universal biomarker that is helpful in the early diagnosis, prognostic prediction, and outcome monitoring of glomerular injury. Measurement of urinary ANXA1 protein levels can help in differentiating MCD from other types of glomerular disorders.
    Disease markers 01/2014; 2014:854163. DOI:10.1155/2014/854163 · 1.56 Impact Factor
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