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Role and Interactions of Annexin A1 and Oestrogens in the Manifestation of Sexual Dimorphisms in Cerebral and Systemic Inflammation

Overview
Journal Br J Pharmacol
Publisher Wiley
Specialty Pharmacology
Date 2012 Aug 18
PMID 22897118
Citations 9
Authors
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Abstract

Background And Purpose: Gender differences in inflammation are well described, with females often showing more robust, oestrogen-associated responses. Here, we investigated the influence of gender, oestrogen and the anti-inflammatory protein annexin A1 (AnxA1) on lipopolysaccharide (LPS)-induced leukocyte-endothelial cell interactions in murine cerebral and mesenteric microvascular beds.

Experimental Approach: Intravital microscopy was used to visualize and quantify the effects of LPS (10 μg·per mouse i.p.) on leukocyte-endothelial interactions in male and female wild-type (WT) mice. The effects of ovariectomy ± oestrogen replacement were examined in WT and AnxA1-null (AnxA1(-/-) ) female mice.

Key Results: LPS increased leukocyte adherence in the cerebral and mesenteric beds of both male and female WT mice; females showed exacerbated responses in the brain versus males, but not the mesentery. Ovariectomy further enhanced LPS-induced adhesion in the brain but not the mesentery; its effects were reversed by oestrogen treatment. OVX AnxA1(-/-) mice also showed exaggerated adhesive responses to LPS in the brain. However, these were unresponsive to ovariectomy and, paradoxically, responded to oestrogen with a pronounced increase in basal and LPS-induced leukocyte adhesion in the cerebrovasculature.

Conclusions And Implications: Our data confirm the fundamental role of AnxA1 in limiting the inflammatory response in the central and peripheral microvasculature. They also (i) show that oestrogen acts via an AnxA1-dependent mechanism to protect the cerebral, but not the mesenteric, vasculature from the damaging effects of LPS and (ii) reveal a paradoxical and potentially toxic effect of the steroid in potentiating the central response to LPS in the absence of AnxA1.

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Estrogen Promotes Pro-resolving Microglial Behavior and Phagocytic Cell Clearance Through the Actions of Annexin A1.

Loiola R, Wickstead E, Solito E, McArthur S Front Endocrinol (Lausanne). 2019; 10:420.

PMID: 31297095 PMC: 6607409. DOI: 10.3389/fendo.2019.00420.


References
1.
Jones K, de Kretser D, Patella S, Phillips D . Activin A and follistatin in systemic inflammation. Mol Cell Endocrinol. 2004; 225(1-2):119-25. DOI: 10.1016/j.mce.2004.07.010. View

2.
DIsanto M, Vitiello M, Raieta K, Galdiero M, Galdiero M . Prolactin modulates IL-8 production induced by porins or LPS through different signaling mechanisms. Immunobiology. 2004; 209(7):523-33. DOI: 10.1016/j.imbio.2004.06.001. View

3.
Young K, Hirst W, Solito E, Wilkin G . De novo expression of lipocortin-1 in reactive microglia and astrocytes in kainic acid lesioned rat cerebellum. Glia. 1999; 26(4):333-43. DOI: 10.1002/(sici)1098-1136(199906)26:4<333::aid-glia7>3.0.co;2-s. View

4.
Scotland R, Stables M, Madalli S, Watson P, Gilroy D . Sex differences in resident immune cell phenotype underlie more efficient acute inflammatory responses in female mice. Blood. 2011; 118(22):5918-27. PMC: 5363818. DOI: 10.1182/blood-2011-03-340281. View

5.
Henninger D, Panes J, Eppihimer M, Russell J, Gerritsen M, Anderson D . Cytokine-induced VCAM-1 and ICAM-1 expression in different organs of the mouse. J Immunol. 1997; 158(4):1825-32. View