title: 17 Beta-estradiol normalizes Toll receptor 4, mitogen activated protein kinases and inflammatory response in epidermal keratinocytes following trauma-hemorrhage.
abstract: Trauma-hemorrhage produces immunodepression in males but not in proestrus females and this difference is due to the presence of high estrogen in proestrus females. Although skin is the largest immunological organ of the body and is considered the first line of defense, no study to-date has examined whether trauma-hemorrhage has any effects on keratinocytes which are the major epidermal cell type (>90%) of skin. We therefore examined whether epidermal keratinocytes inflammatory response and the signal transduction pathways involved in the inflammatory response are altered following trauma-hemorrhage. C3H/HeN mice were subjected to trauma-hemorrhage and 2h thereafter; keratinocytes were harvested and stimulated with LPS for 24h (5 microg/ml). Inflammatory mediators, Toll-like receptor (TLR) and myeloid differentiation adaptor protein (MyD88) expression, and the activation of mitogen-activated protein kinase (MAPK) were determined. Trauma-hemorrhage increased the production of IL-6, IL-10, IL-12 and TNF-alpha enhanced the expression of TLR4, MyD88 as well as the activation of MAPK proteins (p38, ERK and JNK) in epidermal keratinocytes. However, administration of a single dose of 17beta-estradiol following trauma-hemorrhage prevented the increase in these inflammatory parameters under those conditions. These findings suggest that 17beta-estradiol normalizes epidermal keratinocytes inflammatory responses following trauma-hemorrhage by preventing the upregulation of TLR4-mediated MAPK activation.
authors.affiliation: Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294-0019, USA.
authors.forename: Fariba
authors.initials: F
authors.lastname: Moeinpour
authors.forename: Mashkoor A
authors.initials: MA
authors.lastname: Choudhry
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawasaki
authors.forename: Laura
authors.initials: L
authors.lastname: Timares
authors.forename: Martin G
authors.initials: MG
authors.lastname: Schwacha
authors.forename: Kirby I
authors.initials: KI
authors.lastname: Bland
authors.forename: Irshad H
authors.initials: IH
authors.lastname: Chaudry
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004817:Epidermis / Q000201:enzymology / Q000293:injuries* / Q000378:metabolism / Q000473:pathology*; D004958:Estradiol / Q000502:physiology*; D006470:Hemorrhage / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D007249:Inflammation / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D051197:Toll-Like Receptor 4; D004958:Estradiol; D020928:Mitogen-Activated Protein Kinases