Breast milk lactoferrin regulates gene expression by binding bacterial DNA CpG motifs but not genomic DNA promoters in model intestinal cells.

Pediatric Research
Peter MulliganIan R Sanderson

Abstract

High-affinity binding of DNA by lactoferrin (LF) is an established phenomenon, but the biologic function of this interaction remains unclear. LF is an abundant breast milk protein (12.5-87.5 micromol/L) and is resistant to digestion in the infant gut. Regulation of gene expression by LF appears to be a major activity, particularly in modulating immune responses. We hypothesized that LF binding to DNA is a mechanism of gene regulation and aimed to identify the mechanism and physiologic sites of this activity. Our studies focused on two major biologic compartments of DNA: LF binding to proinflammatory bacterial DNA sequences (CpG motifs) in extracellular compartments and LF binding to genomic DNA promoters in the nucleus. LF 0.5 mmol/L inhibited CpG motif-induced nuclear factor-kappaB (NF-kappaB) activation and interleukin (IL)-8 and IL-12 cytokine gene transcription in B cells. Intestinal epithelial cells were unresponsive to CpG motifs. However, significant LF transferred across M cell-like monolayers, specialized epithelial cells that transcytose intact macromolecules to underlying B-cell follicles in the intestine. LF did not activate gene expression by binding to putative response elements in epithelial and lymphoid cells. N...Continue Reading

References

Oct 1, 1978·The Journal of Experimental Medicine·H E BroxmeyerM de Sousa
Apr 1, 1977·Journal of Molecular Biology·E N Baker, S V Rumball
Dec 1, 1992·Journal of Cellular Physiology·C GarréR Ravazzolo
Jun 11, 1971·European Journal of Biochemistry·P QuerinjeanJ F Heremans
Sep 1, 1995·Immunology Today·J Brock
Sep 1, 1995·The Journal of Cell Biology·A H CorbettP A Silver
Dec 1, 1995·Molecular Biology of the Cell·J M SidorovaL L Breeden
Feb 4, 1997·Proceedings of the National Academy of Sciences of the United States of America·R SchubbertW Doerfler
Sep 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·Y OhnoI R Sanderson
Jun 17, 1999·FEBS Letters·T G KanyshkovaG A Nevinsky
Jan 21, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·G HartmannA M Krieg
Feb 19, 2000·Current Opinion in Microbiology·A Vazquez-Torres, F C Fang
Aug 18, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·B E BritiganA M Krieg
Sep 21, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·F TakeshitaD M Klinman

❮ Previous
Next ❯

Citations

Jan 12, 2008·World Journal of Gastroenterology : WJG·Natasha-A KoloskiGraham Radford-Smith
Apr 26, 2014·Nutrients·Elvira VerduciMarcello Giovannini
May 3, 2014·Acta Pharmacologica Sinica·Tania Siqueiros-CendónQuintín Rascón-Cruz
May 31, 2014·Clinics in Perinatology·Brett M Jakaitis, Patricia W Denning
Sep 25, 2012·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Elena T ZakharovaVadim B Vasilyev
Nov 13, 2009·Nutrition Reviews·Susanna Cunningham-RundlesJeffrey M Perlman
Mar 27, 2010·Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology·Dani-Louise DixonAndrew D Bersten
Jan 18, 2012·JPEN. Journal of Parenteral and Enteral Nutrition·David H Adamkin
May 12, 2018·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·E T ZakharovaV B Vasilyev
Nov 6, 2018·Current Pediatric Reviews·Catalina Bazacliu, Josef Neu
Feb 21, 2014·The Journal of Nutrition·Sarah S ComstockSharon M Donovan
Dec 7, 2016·Environmental Epigenetics·Peter D FransquetUNKNOWN Triple B Research Consortium
Feb 6, 2021·Nutrients·Elvira VerduciGian Vincenzo Zuccotti
Mar 7, 2021·Nutrients·Nathalie AcevedoBetty C A M van Esch
Apr 6, 2020·Food Research International·Iramaia Angelica Neri-Numa, Glaucia Maria Pastore

❮ Previous
Next ❯

Related Concepts

Related Feeds

B cells: Gene Expression

B lymphocytes are white blood cells that play a role in the adaptive immune system by secreting antibodies. Here is the latest research on gene expression in B cells.