17beta-Estradiol inhibits keratinocyte-derived chemokine production following trauma-hemorrhage.
Neutrophil infiltration is a key step in the development of organ dysfunction following trauma-hemorrhage (T-H). Although we have previously shown that 17beta-estradiol (E2) prevents neutrophil infiltration and organ damage following T-H, the mechanism by which E2 inhibits neutrophil transmigration remains unknown. We hypothesized that E2 prevents neutrophil infiltration via modulation of keratinocyte-derived chemokine (KC), a major attractant for neutrophils. To examine this, male C3H/HeN mice were subjected to T-H or sham operation and thereafter resuscitated with Ringer lactate and E2 (1 mg/kg body wt) or vehicle. Animals were killed 2 h after resuscitation, and Kupffer cells were isolated. Plasma levels and Kupffer cell production capacities of KC, TNF-alpha, and IL-6 were determined by BD Cytometric Bead Arrays; lung mRNA expression of KC was measured with real-time PCR; myeloperoxidase activity assays were performed to determine neutrophil infiltration, and organ damage was assessed by edema formation. Treatment with E2 decreased systemic levels and restored Kupffer cell production of KC, TNF-alpha, and IL-6, as well as KC gene expression and protein in the lung. This was accompanied with a decrease in neutrophil infiltration and edema formation in the lung. These results suggest that E2 prevents lung neutrophil infiltration and organ damage in part by decreasing KC during posttraumatic immune response.
Frink
Michael
M
Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294-0019, USA.
Thobe
Bjoern M
BM
Hsieh
Ya-Ching
YC
Choudhry
Mashkoor A
MA
Schwacha
Martin G
MG
Bland
Kirby I
KI
Chaudry
Irshad H
IH
D000818:Animals; D018925:Chemokines / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D004487:Edema; D004958:Estradiol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006470:Hemorrhage / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D015603:Keratinocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D007728:Kupffer Cells / Q000187:drug effects; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014947:Wounds and Injuries / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*
D018925:Chemokines; D012333:RNA, Messenger; D004958:Estradiol; D009195:Peroxidase