Joanna B. Goldberg, PhD
Role of H. pylori lipopolysaccharide in inflammation and innate immunity
The major focus of the Goldberg laboratory is determining the molecular mechanisms of bacteria pathogens. One of the ongoing projects is to understand how the interaction of Helicobacter pylori with human epithelial cells can lead to a chronic infection resulting in gastritis, ulcer development and/or gastric cancer. Joanna B. Goldberg, Ph.D. and Mike Smith, Ph.D., The Goldberg and Smith laboratories are working together to understand the interaction of H. pylori and the innate immune system. The experimental system involves tissue culture models of infection that have allowed the identification of TLR2 and TLR5, and not TLR4 as important for the IL-8 response from epithelial cells (Smith, M. F., A. Mitchell, G. Li, S. Ding, A. M. Fitzmaurice, K. Ryan, S. Crowe, and J. B. Goldberg. 2003. TLR2 and TLR5, but not TLR4, are required for Helicobacter pylori-induced NF-kB activation and chemokine expression by epithelial cells. Journal of Biological Chemistry 278:32552-32560). This effort formed the basis of an NIH R01 grant awarded to Dr. Goldberg (with Dr. Smith as a co-PI).
Recent studies have used microarray analysis to determine the genes that are turned on in a TLR-dependent manner after infection with H. pylori (Ding, S. Z., A. M. Torok, M. F. Smith, Jr., and J. B. Goldberg. 2005. Toll-like receptor 2-mediated gene expression in epithelial cells during Helicobacter pylori infection. Helicobacter 10:193-204). Ongoing studies include the control of the cell cycle by H. pylori and its regulation by mitogen-activated protein kinases (MAPK).
Joanna B. Goldberg, Ph.D. and Amy H. Bouton, Ph.D., Data in the literature and that generated in the Goldberg laboratory suggested that mitogen-activated protein (MAP) kinases were activated in response to H. pylori infection. Because of this, collaboration was initiated with Dr. Amy Bouton, who studies cell signaling pathways. They were able to monitor the activation of three MAPK family members and found that p38, JNK, and ERK were activated after H. pylori infection of epithelial cells and that the activation of p38 was enhanced in the presence of TLR2 and TLR5. Further studies showed that the MAPK activation correlated with the secretion of IL-8 from these cells, implicating this activation in the inflammatory response to this pathogen. These results have recently been published (Torok, A. M., A. H. Bouton, and J. B. Goldberg. 2005. Helicobacter pylori induces interleukin-8 secretion by Toll-like receptor 2- and Toll-like receptor 5-dependent and independent pathways. Infection and Immunity, 73:1523-1531).