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Birkhuser Verlag, Basel, 2007
Inamm. res. 56 (2007) 2692731023-3830/07/070269-5DOI 10.1007/s00011-007-6198-z Inammation Research
ReviewModulation of the inammatory response by estrogens with focus on the endothelium and its interactions with leukocytes
B.-O. Nilsson
Department of Experimental Medical Science, Division of Vascular and Airway Research, Unit of Vascular Physiology, Lund University, BMC D12, 221 84 Lund, Sweden, Fax: ++46 46 2224546
Received 28 November 2006; returned for revision 31 January 2007; accepted by I. Ahnfelt-Rnne 20 March 2007
Abstract. Gender differences and variations in inamma-tory disease (e. g. atherosclerosis, neurological disorders, periodontitis and rheumatoid arthritis) severity with female sex hormone level have been reported, suggesting that female sex hormones modulate the inammatory response. Estrogens act on gene transcription via estrogen receptors a and b. Identication of estrogen-regulated genes is a matter of great interest since it will contribute signicantly to the understanding of the physiological importance of estrogens. Anti-inammatory as well as pro-inammatory responses to estrogens have been reported. Data have been presented showing that estrogens down-regulate the expression of adhesion and chemokine molecules in response to inammation promoters in various experimental systems. Functional data show that estrogen treatment attenuates recruitment and adhesion of leukocytes to the endothelium induced by inammation promoters offering a possible mechanism by which estrogens exert an anti-inammatory effect. These effects of estrogens, with focus on the interactions of monocytes with the vascular endothelium, are highlighted in this review.
Key words: Estrogen Chemokines Cytokines Endothelium Nitric oxide synthase
Introduction
The female sex hormone estrogen regulates function and development of its classical target organs, such as breast and uterus, but estrogens have also been reported to affect many other organs and tissues [1, 2]. Evidence suggests that estrogens affect the immune system and the processes associated with inammation as reviewed by e. g. Obendorf and Patchev [3], Lang [4], Cutolo et al. [5] and Paavonen [6].
The cloning of estrogen receptor (ER) a was reported in 1986 [7, 8]. Ten years later a second ER was identied in rat [9], mouse [10] and human [11] and named ERb. The most biological important estrogen 17b-estradiol binds to both ERa and ERb with a similar high afnity (Kd = 0.1 nM for ERa protein and 0.4 nM for ERb protein) [12]. ERa and ERb show ER subtype...