Anti‐inflammatory actions of an N‐terminal peptide from human lipocortin 1

Cirino, Giuseppe; Cicala, Carla; Sorrentino, L.; Ciliberto, Gennaro; Arpaia, G.; Perretti, Mauro; Flower, Roderick J.

doi:10.1111/j.1476-5381.1993.tb12843.x

Cited by 76 publications

(40 citation statements)

References 10 publications

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“…Since the study was designed to observe phorbol myristate acetate-induced c-fos activation, it is likely that several factors other than cPLA 2 also participate in this process. The importance of the N-terminal region in mediation of the anti-inflammatory function of glucocorticoids and inflammatory signal transduction has been reported by Flower and co-workers (41)(42)(43). In the study of neutrophil migration, a mechanism has been proposed that the N-terminus of ANX-I binds to a receptor-like molecule on the surface of the neutrophils (44).…”

Section: Fig 2 Production Of Gst-anx-i and Its Deletion Mutants In Ementioning

confidence: 97%

Inhibition of Cytosolic Phospholipase A2 by Annexin I

Kim

Rhee

et al. 2001

Journal of Biological Chemistry

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Section: Fig 2 Production Of Gst-anx-i and Its Deletion Mutants In Ementioning

confidence: 97%

Inhibition of Cytosolic Phospholipase A2 by Annexin I

Kim

Rhee

et al. 2001

Journal of Biological Chemistry

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“…12 This contrasts with the situation within the host defence system where annexin 1 shows the full efficacy of the parent protein. 22 The nature of the annexin 1 receptor is also obscure. It has recently been suggested that the formyl peptide receptor (FPR) maybe important in this regard.…”

Section: Mechanism Of Annexin 1 Actionmentioning

confidence: 99%

Annexin 1: a paracrine/juxtacrine mediator of glucorticoid action in the neuroendocrine system

Buckingham

Solito

John

et al. 2003

Cell Biochemistry & Function

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Glucocorticoids (GCs) play an essential role in the maintenance of homeostasis. In normal circumstances their secretion is tightly regulated by a complex servo mechanism through which the steroids suppress the synthesis and release of ACTH and its hypothalamic releasing factors (CRH and AVP) and thereby reduce the positive drive to the adrenal cortex. The feedback actions of GCs on hormone release develop rapidly (within minutes), well before any changes in hormone synthesis are apparent. By using immunoneutralization, gene targeting and pharmacological strategies in in vivo and in vitro models, we have identified annexin 1, a Ca 2þ -and phospholipid-binding protein, as a key mediator of the early inhibitory actions of GCs on peptide release. This brief review outlines this work and describes molecular and cellular studies which have provided insight into the mechanism of annexin 1-dependent GC signalling in the neuroendocrine system.

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“…It is required for the inhibition of NF-B activity by anti-inflammatory drugs (13) and has recently been shown to be a potential biomarker of therapeutic efficacy for IBD (14). The N-terminal region of annexin A1 comprising residues 2-26 (Ac2-26) has been well studied (15,16) and appears to have the same biological effects as the full-length protein (17). Analysis of a series of peptides based on the N-terminal sequence of annexin A1 showed that MC-12 (Ac-Gln-Ala-Trp) was the most potent inhibitor of NF-B activity in SW480 cells (13).…”

mentioning

confidence: 99%

An engineered cyclic peptide alleviates symptoms of inflammation in a murine model of inflammatory bowel disease

Caceres

Bansal

Navarro

et al. 2017

Journal of Biological Chemistry

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Edited by Wolfgang PetiInflammatory bowel diseases (IBDs) are a set of complex and debilitating diseases for which there is no satisfactory treatment. Recent studies have shown that small peptides show promise for reducing inflammation in models of IBD. However, these small peptides are likely to be unstable and rapidly cleared from the circulation, and therefore, if not modified for better stability, represent non-viable drug leads. We hypothesized that improving the stability of these peptides by grafting them into a stable cyclic peptide scaffold may enhance their therapeutic potential. Using this approach, we have designed a novel cyclic peptide that comprises a small bioactive peptide from the annexin A1 protein grafted into a sunflower trypsin inhibitor cyclic scaffold. We used native chemical ligation to synthesize the grafted cyclic peptide. This engineered cyclic peptide maintained the overall fold of the naturally occurring cyclic peptide, was more effective at reducing inflammation in a mouse model of acute colitis than the bioactive peptide alone, and showed enhanced stability in human serum. Our findings suggest that the use of cyclic peptides as structural backbones offers a promising approach for the treatment of IBD and potentially other chronic inflammatory conditions. Inflammatory bowel diseases (IBDs)3 are a set of chronic inflammatory disorders of the gastrointestinal tract; the two major forms are ulcerative colitis and Crohn's disease (1). Although there are several medications on the market for IBD, they generally only provide temporary relief, and 70% of IBD patients require surgical intervention (2). Because the current treatments are not satisfactory, new drug leads are being sought from a range of sources, including small molecules from plants and bioactive regions of larger proteins (3-6).Intriguingly, several small peptides, some comprising only three residues, have been shown to be effective in the treatment of experimental colitis in mice (7-11). One example is a tripeptide (MC-12) derived from annexin A1, a calcium-dependent phospholipid-binding, anti-inflammatory protein (12). Annexin A1 mediates expression of cytokines such as TNF-␣, IL-6, and IL-10. It is required for the inhibition of NF-B activity by anti-inflammatory drugs (13) and has recently been shown to be a potential biomarker of therapeutic efficacy for IBD (14). The N-terminal region of annexin A1 comprising residues 2-26 (Ac2-26) has been well studied (15, 16) and appears to have the same biological effects as the full-length protein (17). Analysis of a series of peptides based on the N-terminal sequence of annexin A1 showed that MC-12 (Ac-Gln-Ala-Trp) was the most potent inhibitor of NF-B activity in SW480 cells (13).Small peptides such as MC-12 are likely to be unstable and not viable drug leads, supported by the finding that high doses (25 mg/kg) of MC-12 were required to elicit an in vivo response in mouse colitis models, and it was more effective when injected compared with oral administration (18). Improving t...

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Anti‐inflammatory actions of an N‐terminal peptide from human lipocortin 1

Cited by 76 publications

References 10 publications

Inhibition of Cytosolic Phospholipase A2 by Annexin I

Inhibition of Cytosolic Phospholipase A2 by Annexin I

Annexin 1: a paracrine/juxtacrine mediator of glucorticoid action in the neuroendocrine system

An engineered cyclic peptide alleviates symptoms of inflammation in a murine model of inflammatory bowel disease

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