PMID- 28573506 OWN - NLM STAT- MEDLINE DCOM- 20170905 LR - 20220318 IS - 1573-2568 (Electronic) IS - 0163-2116 (Print) IS - 0163-2116 (Linking) VI - 62 IP - 8 DP - 2017 Aug TI - Estradiol Has Differential Effects on Acute Colonic Inflammation in the Presence and Absence of Estrogen Receptor beta Expression. PG - 1977-1984 LID - 10.1007/s10620-017-4631-x [doi] AB - BACKGROUND: Inflammatory bowel disease (IBD) increases the risk of developing colon cancer. This risk is higher in men compared to women, implicating a role for female hormones in the protection against this disease. Studies from our laboratory demonstrated that estradiol (E(2)) protects against inflammation-associated colon tumor formation when administered following chemical carcinogen and induction of chronic colitis. AIM: This study seeks to better understand the effect of E(2) on acute colitis in the presence and absence of estrogen receptor beta (ERbeta). METHODS: Inflammation was induced by 2,4,6-trinitrobenzenesulfonic acid in wild-type (WT) and ERbeta knockout (ERbetaKO) mice implanted with a control or E(2)-containing pellet and killed 5 days later. Inflammation and injury were scored by a pathologist. Apoptosis and proliferation were assessed by immunohistochemistry. Cytokines were measured by multiplex analysis. RESULTS: E(2) treatment reduced inflammation in the middle colon in WT mice and the distal colon in ERbetaKO mice compared to control mice. WT mice had reduced IL-6, IL-12, IL-17, GM-CSF, IFN-gamma, MCP-1, MIP-1alpha, and TNF-alpha, and ERbetaKO had reduced IL-6 and IFN-gamma expression in response to E(2). Injury scores were lower in E(2)-treated ERbetaKO mice compared to control ERbetaKO mice. ERbetaKO mice had increased proliferation in the basal third of crypts in the distal colon and decreased apoptosis in the proximal colon. CONCLUSIONS: These data suggest that E(2) has differential protective effects against acute colitis in the presence or absence of ERbeta and provide insight into how E(2) may protect against IBD. FAU - Armstrong, Cameron M AU - Armstrong CM AD - Department of Nutrition and Food Science, Texas A&M University, 214B Cater Mattil, 2253 TAMU, College Station, TX, 77843, USA. FAU - Allred, Kimberly F AU - Allred KF AD - Department of Nutrition and Food Science, Texas A&M University, 214B Cater Mattil, 2253 TAMU, College Station, TX, 77843, USA. FAU - Weeks, Brad R AU - Weeks BR AD - Department of Veterinary Pathobiology, Texas A&M University, College Station, TX, USA. FAU - Chapkin, Robert S AU - Chapkin RS AD - Department of Nutrition and Food Science, Texas A&M University, 214B Cater Mattil, 2253 TAMU, College Station, TX, 77843, USA. FAU - Allred, Clinton D AU - Allred CD AD - Department of Nutrition and Food Science, Texas A&M University, 214B Cater Mattil, 2253 TAMU, College Station, TX, 77843, USA. callred@tamu.edu. LA - eng GR - P30 ES023512/ES/NIEHS NIH HHS/United States GR - R01 CA202697/CA/NCI NIH HHS/United States GR - R35 CA197707/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170601 PL - United States TA - Dig Dis Sci JT - Digestive diseases and sciences JID - 7902782 RN - 0 (Cytokines) RN - 0 (Estrogen Receptor beta) RN - 0 (Estrogens) RN - 0 (Inflammation Mediators) RN - 4TI98Z838E (Estradiol) RN - 8T3HQG2ZC4 (Trinitrobenzenesulfonic Acid) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Cell Proliferation/drug effects MH - Colitis/chemically induced/*drug therapy/*metabolism MH - Colonic Neoplasms/chemically induced/prevention & control MH - Cytokines/analysis/drug effects MH - Estradiol/*pharmacology MH - Estrogen Receptor beta/analysis/genetics/*metabolism MH - Estrogens/*pharmacology MH - Female MH - Immunohistochemistry MH - Inflammation Mediators/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Trinitrobenzenesulfonic Acid PMC - PMC5751962 MID - NIHMS929742 OTO - NOTNLM OT - Colon cancer OT - Crohn's disease OT - Estradiol OT - Estrogen receptor beta OT - Inflammation COIS- Conflict of interest None of the authors have any conflicts of interest to declare. EDAT- 2017/06/03 06:00 MHDA- 2017/09/07 06:00 PMCR- 2018/01/03 CRDT- 2017/06/03 06:00 PHST- 2017/03/01 00:00 [received] PHST- 2017/05/24 00:00 [accepted] PHST- 2017/06/03 06:00 [pubmed] PHST- 2017/09/07 06:00 [medline] PHST- 2017/06/03 06:00 [entrez] PHST- 2018/01/03 00:00 [pmc-release] AID - 10.1007/s10620-017-4631-x [pii] AID - 10.1007/s10620-017-4631-x [doi] PST - ppublish SO - Dig Dis Sci. 2017 Aug;62(8):1977-1984. doi: 10.1007/s10620-017-4631-x. Epub 2017 Jun 1.