title: The expression of REG 1A and REG 1B is increased during acute amebic colitis.
abstract: Entamoeba histolytica, a protozoan parasite, is an important cause of diarrhea and colitis in the developing world. Amebic colitis is characterized by ulceration of the intestinal mucosa. We performed microarray analysis of intestinal biopsies during acute and convalescent amebiasis in order to identify genes potentially involved in tissue injury or repair. Colonic biopsy samples were obtained from 8 patients during acute E. histolytica colitis and again 60 days after recovery. Gene expression in the biopsies was evaluated using microarray, and confirmed by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). REG 1A and REG 1B were the most up-regulated of all genes in the human intestine in acute versus convalescent E. histolytica disease: as determined by microarray, the levels of induction were 7.4-fold and 10.7 fold for REG 1A and B; p=0.003 and p=0.006 respectively. Increased expression of REG 1A and REG 1B protein in the colonic crypt epithelial cells during acute amebiasis was similarly observed by immunohistochemistry. Because REG 1 protein is anti-apoptotic and pro-proliferative, and since E. histolytica induces apoptosis of the intestinal epithelium as part of its disease process, we next tested if REG 1 might be protective during amebiasis by preventing parasite-induced apoptosis. Intestinal epithelial cells from REG 1-/- mice were found to be more susceptible to spontaneous, and parasite-induced, apoptosis in vitro (p=0.03). We concluded that REG 1A and REG 1B were upregulated during amebiasis and may function to protect the intestinal epithelium from parasite-induced apoptosis.
authors.affiliation: Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA 22908, USA. kmp5v@virginia.edu
authors.forename: Kristine M
authors.initials: KM
authors.lastname: Peterson
authors.forename: Xiaoti
authors.initials: X
authors.lastname: Guo
authors.forename: Abdel G
authors.initials: AG
authors.lastname: Elkahloun
authors.forename: Dinesh
authors.initials: D
authors.lastname: Mondal
authors.forename: Pradip K
authors.initials: PK
authors.lastname: Bardhan
authors.forename: Akira
authors.initials: A
authors.lastname: Sugawara
authors.forename: Priya
authors.initials: P
authors.lastname: Duggal
authors.forename: Rashidul
authors.initials: R
authors.lastname: Haque
authors.forename: William A
authors.initials: WA
authors.lastname: Petri
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D017209:Apoptosis; D003106:Colon / Q000469:parasitology / Q000473:pathology; D004404:Dysentery, Amebic / Q000235:genetics / Q000469:parasitology*; D004748:Entamoeba histolytica / Q000472:pathogenicity; D004749:Entamoebiasis / Q000235:genetics / Q000469:parasitology*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D055786:Gene Knockout Techniques; D006801:Humans; D007422:Intestines / Q000469:parasitology / Q000473:pathology; D051847:Lithostathine / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000235:genetics; D055815:Young Adult
chemical_list: D051847:Lithostathine; C497617:REG1A protein, human; C497618:REG1B protein, human; D012313:RNA