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Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2014-02-26T17:24:21Z No. of bitstreams: 1 WOS000235597700037.pdf: 609984 bytes, checksum: 7b36f6886f88f9ea0b2c7ecaf7460c92 (MD5) Made available in DSpace on 2014-02-26T17:24:21Z (GMT). No. of bitstreams: 1 WOS000235597700037.pdf: 609984 bytes, checksum: 7b36f6886f88f9ea0b2c7ecaf7460c92 (MD5) Previous issue date: 2006-02-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T14:01:32Z No. of bitstreams: 1 WOS000235597700037.pdf: 609984 bytes, checksum: 7b36f6886f88f9ea0b2c7ecaf7460c92 (MD5) Made available in DSpace on 2014-05-20T14:01:32Z (GMT). No. of bitstreams: 1 WOS000235597700037.pdf: 609984 bytes, checksum: 7b36f6886f88f9ea0b2c7ecaf7460c92 (MD5) Previous issue date: 2006-02-01 The mode of action of annexin A1 (ANXA1) is poorly understood. By using rapid subtraction hybridization we studied the effects of human recombinant ANXA1 and the N-terminal ANXA1 peptide on gene expression in a human larynx cell line. Three genes showed strong downregulation after treatment with ANXA1. In contrast, expression of CCR10, a seven transmembrane G-protein coupled receptor for chemokine CCL27 involved in mucosal immunity, was increased. Moreover the reduction in CCR10 expression induced by ANXA1 gene deletion was rescued by intravenous treatment with low doses of ANXA1. These findings provide new evidence that ANXA1 modulates gene expression. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. Univ London Imperial Coll Sci Technol & Med, Fac Med, Div Neurosci & Mental Hlth, Dept Cellular & Mol Neurosci, London W12 0NN, England UNESP, São Paulo State Univ, IBILCE, Sao Jose do Rio Preto, SP, Brazil USP, Fac Med, Ribeirao Preto, Brazil UNESP, São Paulo State Univ, IBILCE, Sao Jose do Rio Preto, SP, Brazil

Obesity is a risk factor for sepsis morbidity and mortality, whereas the hypothalamic–pituitary–adrenal (HPA) axis plays a protective role in the body's defence against sepsis. Sepsis induces a profound systemic immune response and cytokines serve as excellent markers for sepsis as they act as mediators of the immune response. Evidence suggests that the adipokine leptin may play a pathogenic role in sepsis. Mouse endotoxaemic models present with elevated leptin levels and exogenously added leptin increased mortality whereas human septic patients have elevated circulating levels of the soluble leptin receptor (Ob-Re). Evidence suggests that leptin can inhibit the regulation of the HPA axis. Thus, leptin may suppress the HPA axis, impairing its protective role in sepsis. We hypothesised that leptin would attenuate the HPA axis response to sepsis. We investigated the direct effects of an i.p. injection of 2 mg/kg leptin on the HPA axis response to intraperitoneally injected 25 μg/kg lipopolysaccharide (LPS) in the male Wistar rat. We found that LPS potently activated the HPA axis, as shown by significantly increased plasma stress hormones, ACTH and corticosterone, and increased plasma interleukin 1β (IL1β) levels, 2 h after administration. Pre-treatment with leptin, 2 h before LPS administration, did not influence the HPA axis response to LPS. In turn, LPS did not affect plasma leptin levels. Our findings suggest that leptin does not influence HPA function or IL1β secretion in a rat model of LPS-induced sepsis, and thus that leptin is unlikely to be involved in the acute-phase endocrine response to bacterial infection in rats.