Annexin 1 and neutrophil apoptosis

2004 ◽  
Vol 32 (3) ◽  
pp. 507-510 ◽  
Author(s):  
M. Perretti ◽  
E. Solito

ANXA1 (annexin 1), a member of the ‘annexin’ family of calcium- and phospholipid-binding proteins, was originally identified as an endogenous mediator of the anti-inflammatory actions of glucocorticoids. However, this protein exerts multiple inhibitory effects on the host inflammatory response, including a preferential regulation of the adhesion step of blood-borne neutrophil within the microenvironment of an inflamed vasculature. It is now emerging that ANXA1 is endowed with other roles, since the protein is abundant in inflammatory exudates as it is produced and released by the extravasated neutrophil. In the present paper, we review the novel proapoptotic effect of ANXA1 and discuss its potential with respect to the pathophysiology of inflammation and leucocyte recruitment.

2009 ◽  
Vol 201 (2) ◽  
pp. 169-184 ◽  
Author(s):  
Lucy V Norling ◽  
Mauro Perretti ◽  
Dianne Cooper

A new era of research is being devoted to deciphering endogenous mediators and mechanisms that are in place to resolve the inflammatory response. Accruing evidence indicates that galectins fall into this category of immunoregulatory mediators signifying their use as prospective novel anti-inflammatory agents. The focus of this review is to depict the immunoregulatory bioactivities of three members of the galectin superfamily, Galectin (Gal)-1, Gal-3 and Gal-9. Emphasis is given to the studies investigating the properties of these endogenous lectins. Gal-1, Gal-3 and Gal-9 are emerging as pertinent players in the modulation of acute and chronic inflammatory diseases, autoimmunity and cancer, and thus being increasingly recognised as molecular targets for innovative drug discovery.


Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 530
Author(s):  
Solomiia Kozachok ◽  
Joanna Kolodziejczyk-Czepas ◽  
Svitlana Marchyshyn ◽  
Krzysztof Kamil Wojtanowski ◽  
Grażyna Zgórka ◽  
...  

The work is aimed at phytochemical characterization and In Vitro evaluation of antioxidant actions, anti-inflammatory effects, and cytotoxicity of purified extracts from three rupturewort (Herniaria L.) species, i.e., Herniaria glabra (HG), H. polygama (HP), and H. incana herb (HIh). The total phenolic content established in the purified extracts (PEs) of HIh, HP, and HG was 29.6, 24.0, and 13.0%, respectively. Thirty-eight non-saponin metabolites were identified using LC-HR-QTOF-ESI-MS; however, only 9 were common for the studied Herniaria species. The most abundant phenolic compound in HG-PE was narcissin (7.4%), HP-PE shared 3 major constituents, namely cis-2-hydroxy-4-methoxycinnamic acid 2-O-β-glucoside (cis-GMCA, 5.8%), narcissin (5.4%), and rutin (5.3%). Almost half of HIh phenolic content (14.7%) belonged to oxytroflavoside A (7-O-methylkaempferol-3-O-[3-hydroxy-3-methylglutaryl-(1→6)]-[α-rhamnopyranosyl-(1®2)]-β-galactopyranoside). Antioxidant properties of the Herniaria PEs were evaluated employing an experimental model of human blood plasma, exposed to the peroxynitrite-induced oxidative stress. The assays demonstrated significant reduction of oxidative damage to protein and lipid plasma components (estimated by measurements of 3-nitrotyrosine, protein thiol groups, thiobarbituric acid-reactive substances), and moderate protection of its non-enzymatic antioxidant capacity. Anti-inflammatory properties of the Herniaria PEs were evaluated In Vitro as inhibitory effects against cyclooxygenases (COX-1 and -2) and concanavalin A-induced inflammatory response of the peripheral blood mononuclear cells (PBMCs). None of the studied plants showed inhibitory effects on COXs but all purified extracts partly reduced the release of interleukin 2 (IL-2) and tumor necrosis factor-alpha (TNF-α) from PBMCs, which suggested their prospective ability to up-regulate inflammatory response of the cells. The purified extract from H. glabra turned out to be the most efficient suppressor of PBMCs’ inflammatory response. Additionally, cytotoxicity of purified Herniaria extracts on PBMCs was ruled out based on In Vitro studies.


2003 ◽  
Vol 12 (6) ◽  
pp. 329-337 ◽  
Author(s):  
M. Castro-caldas ◽  
A. F. Mendes ◽  
C. B. Duarte ◽  
M. C. F. Lopes

Aims:Annexin 1 (ANXA1), a member of the annexin family of calcium-binding and phospholipid-binding proteins, is a key mediator of the anti-inflammatory actions of steroid hormones. We have previously demonstrated that, in the human lymphoblastic CCRF-CEM cell line, both the synthetic glucocorticoid hormone, dexamethasone (Dex), and the estrogen hormone, 17β-estradiol (E2β), induce the synthesis of ANXA1, by a mechanism independent of the activation of their nuclear receptors. Recently, it was reported that the gene coding for ANXA1 contains a cAMP-responsive element (CRE). In this work, we investigated whether Dex and E2β were able to induce the activation of CRE binding proteins (CREB) in the CCRF-CEM cells. Moreover, we studied the intracellular signalling pathways involved in CREB activation and ANXA1 synthesis in response to Dex and E2β; namely, the role of cAMP and the p38 mitogen-activated protein kinase (MAPK).Results:The results show that Dex and E2β were as effective as the cAMP analogue, dBcAMP, in inducing CREB activation. On the other hand, dBcAMP induced ANXA1 synthesis as effectively as these steroid hormones. Furthermore, the cAMP antagonist, Rp-8-Br-cAMPS, and the specific p38 MAPK inhibitor, SB203580, effectively prevented Dex-induced, E2β-induced and dBcAMP-induced CREB activation and ANXA1 synthesis.Conclusions:Taken together, our results suggest that, in CCRF-CEM cells, Dex-induced and E2β-induced ANXA1 expression requires the activation of the transcription factor CREB, which in turn seems to be mediated by cAMP and the p38 MAPK. These findings also suggest that, besides the nuclear steroid hormone receptors, other transcription factors, namely CREB, may play important roles in mediating the anti-inflammatory actions of glucocorticoids and oestrogen hormones.


Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
YC Oh ◽  
YH Jeong ◽  
WK Cho ◽  
SJ Lee ◽  
JY Ma

2019 ◽  
Vol 16 (10) ◽  
pp. 1157-1166
Author(s):  
Rodrigo César da Silva ◽  
Fabiano Veiga ◽  
Fabiana Cardoso Vilela ◽  
André Victor Pereira ◽  
Thayssa Tavares da Silva Cunha ◽  
...  

Background: : A new series of O-benzyloximes derived from eugenol was synthesized and was evaluated for its antinociceptive and anti-inflammatory properties. Methods: : The target compounds were obtained in good global 25-28% yields over 6 steps, which led us to identify compounds (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-(4- (methylthio)benzyloxime (8b), (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-4- bromobenzyloxime (8d) and (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-4- (methylsulfonyl)benzyloxime (8f) as promising bioactive prototypes. Results:: These compounds have significant analgesic and anti-inflammatory effects, as evidenced by formalin-induced mice paw edema and carrageenan-induced mice paw edema tests. In the formalin test, compounds 8b and 8f evidenced both anti-inflammatory and direct analgesic activities and in the carrageenan-induced paw edema, with compounds 8c, 8d, and 8f showing the best inhibitory effects, exceeding the standard drugs indomethacin and celecoxib. Conclusion: : Molecular docking studies have provided additional evidence that the pharmacological profile of these compounds may be related to inhibition of COX enzymes, with slight preference for COX-1. These results led us to identify the new O-benzyloxime ethers 8b, 8d and 8f as orally bioactive prototypes, with a novel structural pattern capable of being explored in further studies aiming at their optimization and development as drug candidates.


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