Annexin 1 is Overexpressed and Specifically Secreted During Experimentally Induced Colitis in Rats

Abstract

Annexin 1 is a protein induced by glucocorticoids endowed with extracellular anti‐inflammatory properties. In this study, the local expression and secretion of annexins 1–6, in rat proximal colon, were studied at different times after intracolonic administration of 30 mg trinltrobenzenesulfonic acid in 50% ethanol. Secretion was identified by incubating colonic tissues in a culture medium. The expression of annexins was detected by immunoblotting in tissue homogenates and incubation media. Inflammatory stages were evaluated by measuring myeloperoxidase activity. Annexin 1 expression in colons increased after trinitrobenzenesulfonic acid treatment and was maximal between days 1 to 9, during the cellular stage of the inflammation that corresponded to maximal myeloperoxidase activity. From 12 h to 9 days after trinitrobenzenesulfonic acid/ethanol treatment, annexin 1 was specifically secreted. Annexin 3 was also overexpressed during the cellular stage, but the expression of annexins 2, 4, 5, and 6 was unchanged; none of these annexins were secreted. Annexin 1 was shown to be physiologically secreted because its release was specific, abundant, and not correlated with cellular lysis. Annexin 1 may be considered as a putative candidate in the control of the gut inflammatory processes.

An Annexin 1 N-Terminal Peptide Activates Leukocytes by Triggering Different Members of the Formyl Peptide Receptor Family

“…Such concentrations are higher than annexin 1 levels reported in normal serum. However, annexin 1 expression is induced by glucocorticoids and IL-6 (34 -36) and systemic annexin 1 concentrations have been shown to increase at least 10-fold in a number of inflammatory and infectious diseases (37)(38)(39). Furthermore, leukocytes have been reported to release annexin 1 under certain conditions (40) and thus may produce relatively high concentrations of the protein in their microenvironment.…”

Annexin I Regulates SKCO-15 Cell Invasion by Signaling through Formyl Peptide Receptors

“…Additionally, following inflammatory insults to mucosal tissues, stimulation of epithelial nFPRs by endogenous ligands such as AnxA1 may promote epithelial cell migration events important in wound healing. For example, it has been shown that inflammation of colonic mucosa, as occurring in inflammatory bowel disease, results in increased AnxA1 production and secretion by infiltrating leukocytes (89,90). This secreted AnxA1 could stimulate nFPRs expressed by intestinal epithelial cells and promote restitution.…”

An overview of the effects of annexin 1 on cells involved in the inflammatory process

“…The constitutive expression of ANXA1 mRNA and protein by macrophages has been shown reproducibly by many authors to increase following exposure to GC in vitro and in vivo (Ambrose et al 1992, De Caterina et al 1993, Peers et al 1993, Coméra et al 1995, Perretti & Flower 1996, Yang et al 1998, Hall et al 1999.…”

“…Again, a new and hitherto unappreciated aspect of ANXA1 biology may be explored as a result of these observations. For instance, experimental evidence in animal models as well as in humans indicated marked presence of ANXA1 in inflammatory exudates (Ambrose et al 1990b, Smith et al 1990, Vergnolle et al 1995, suggesting a physiological role for ANXA1 in modulating neutrophil survival at sites of inflammation. In situ hybridization analysis showed de novo ANXA1 synthesis in extravasated neutrophils (Oliani et al 2001a) supporting the concept of feedback control on neutrophil activity.…”