title: Mediation of the immunomodulatory effect of beta-estradiol on inflammatory responses by inhibition of recruitment and activation of inflammatory cells and their gene expression of TNF-alpha and IFN-gamma.
abstract: BACKGROUND
  Estrogen has long been reported to show immunomodulatory effects on immune responses, yet, its specific anti-inflammatory mechanism is not clear.
  
  
  METHODS
  In this study, we analyzed the effects of beta-estradiol (E2), at its contraceptive dose, on both T cell-independent and T cell-dependent inflammations, and the associated immune mechanism, in female mice. The T cell-independent inflammation was locally induced either with an intradermal injection of olive oil in the footpad, or by an intraperitoneal injection of proteose peptone (PP). The T cell-dependent inflammation was induced by an intraperitoneal injection of the purified protein derivatives (PPD).
  
  
  RESULTS
  While E2 inhibited olive oil-induced inflammation as monitored by the decrease in footpad swelling, it did not affect the gene expression of monocyte chemoattractant protein-1 and IL-6 by cells at the inflammatory locus. E2 also inhibited PP-induced inflammation as monitored by the decrease in the number of inflammatory peritoneal exudate cells (PEC) coinciding with a marked decrease in the number of macrophages and granulocytes (Gr. 1+). While E2 did not affect the gene expression of monocyte chemoattractant protein-1 and IL-6 by PP-elicited PEC, it decreased both gene expression and production of TNF-alpha. E2 also decreased the number of cells expressing the lymphocyte function-activated protein-1 in PP-elicited PEC, but not for CD62L. In purified protein derivative-induced T cell-dependent inflammation, E2 decreased the total cellularity of PEC and the relative numbers of CD3+ and CD4+ T cells, and the number of cells expressing the lymphocyte activation markers CD40, CD44, CD69 and IL-2Ralpha in PEC. Furthermore, while E2 did not affect the gene expression of the early T lymphocyte activation protein-1 by PEC, it decreased the gene expression of INF-gamma.
  
  
  CONCLUSIONS
  Collectively, the results suggest that E2-mediated inhibition of inflammatory responses may be due to a combination of suppression of homing and activation of inflammatory cells and their production of TNF-alpha and IFN-gamma.
authors.affiliation: Department of Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan. mohamed_84@hotmail.com
authors.forename: M L
authors.initials: ML
authors.lastname: Salem
authors.forename: M S
authors.initials: MS
authors.lastname: Hossain
authors.forename: K
authors.initials: K
authors.lastname: Nomoto
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D002364:Caseins / Q000633:toxicity; D002465:Cell Movement / Q000276:immunology*; D018932:Chemokine CCL2 / Q000235:genetics; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004487:Edema / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D005528:Foot / Q000473:pathology; D005786:Gene Expression Regulation / Q000276:immunology*; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D000069463:Olive Oil; D010446:Peptide Fragments / Q000633:toxicity; D010938:Plant Oils / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D000276:Adjuvants, Immunologic; D002364:Caseins; D018932:Chemokine CCL2; D018925:Chemokines; D016207:Cytokines; D015850:Interleukin-6; D000069463:Olive Oil; D010446:Peptide Fragments; D010938:Plant Oils; D014409:Tumor Necrosis Factor-alpha; C018135:proteose-peptone; D004958:Estradiol; D007371:Interferon-gamma