Endocrine Abstracts (2001) 2 OC2

LPS ACTS VIA IL-6 TO MODULATE THE EXPRESSION AND PHOSPHORYLATION OF ANNEXIN 1 IN CELL LINES DERIVED FROM THE MICROGLIA OF THE NEUROENDOCRINE SYSTEM

E Solito, A Mulla & J Buckingham


Department of Neuroendocrinology, Imperial College, London, UK.


Annexin 1 (ANXA1, lipocortin 1), a Ca2+ and phospholipid binding protein, is a strong candidate mediator of the interplay between the immune and neuroendocrine systems. Within the neuroendocrine system ANXA1 is expressed in abundance by the non-secretory pituitary folliculo-stellate (FS) cells (1), which show characteristics of resident microglia. We have previously reported that IL-6 up-regulates ANXA1 expression in the liver in vivo and in A549 cells (lung epithelial) in vitro through the trans-activation of c/EBP beta (2,3) and proposed annexin 1 as new acute phase protein. We have also shown that endotoxin increases ANXA1 expression in the rat anterior pituitary gland and hypothalamus (4). In the present study we used RT-PCR, western blot analysis and flow cytometry to examine the effects of LPS on ANXA1 expression and phosphorylation status in a FS cell line (murine TtT/GF) which we have shown to express the LPS receptor, CD14. Our data show that LPS induces de novo ANXA1 expression and causes ser-phosphorylation of the protein in these cells. Its actions are specifically reversed by an anti-IL-6 antibody and therefore dependent on IL-6 and are mediated by CD14, possibly through interaction with the Tlr2 receptor. These findings support a role for ANXA1 as a mediator of immune-neuroendocrine communication.

1. Traverso V, Christian HC, Morris JF & Buckingham JC (1999). Endocrinology 140, 4311-4319.

2. Solito E, de Coupade C, Parente L, Flower R & Russo Marie F (1998). Cytokine 10, 514-521.

3. de Coupade C, Ajuebor MN, Russo-Marie F, Perretti M & Solito E. (2001) Am. J. Pathol (in press).

4. Buckingham JC (1996) Br. J. Pharmacol., 118, 1-19

This work was supported by the Wellcome Trust and MRC.

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