William K. Hu

Publications (2)9.55 Total impact

• Article: Inflammation Anergy in Human Intestinal Macrophages Is Due to Smad-induced IκBα Expression and NF-κB Inactivation

  Lesley E. Smythies, Ruizhong Shen, Diane Bimczok, Lea Novak, Ronald H. Clements, Devin E. Eckhoff, Phillipe Bouchard, Michael D. George, William K. Hu, Satya Dandekar, Phillip D. Smith
  [show abstract] [hide abstract]
  ABSTRACT: Human intestinal macrophages contribute to tissue homeostasis in noninflamed mucosa through profound down-regulation of pro-inflammatory cytokine release. Here, we show that this down-regulation extends to Toll-like receptor (TLR)-induced cytokine release, as intestinal macrophages expressed TLR3–TLR9 but did not release cytokines in response to TLR-specific ligands. Likely contributing to this unique functional profile, intestinal macrophages expressed markedly down-regulated adapter proteins MyD88 and Toll interleukin receptor 1 domain-containing adapter-inducing interferon β, which together mediate all TLR MyD88-dependent and -independent NF-κB signaling, did not phosphorylate NF-κB p65 or Smad-induced IκBα, and did not translocate NF-κB into the nucleus. Importantly, transforming growth factor-β released from intestinal extracellular matrix (stroma) induced identical down-regulation in the NF-κB signaling and function of blood monocytes, the exclusive source of intestinal macrophages. Our findings implicate stromal transforming growth factor-β-induced dysregulation of NF-κB proteins and Smad signaling in the differentiation of pro-inflammatory blood monocytes into noninflammatory intestinal macrophages.
  Journal of Biological Chemistry 06/2010; 285(25):19593-19604. · 4.77 Impact Factor
• Source

  Available from: Michael D George

  Article: Inflammation anergy in human intestinal macrophages is due to Smad-induced IkappaBalpha expression and NF-kappaB inactivation.

  Lesley E Smythies, Ruizhong Shen, Diane Bimczok, Lea Novak, Ronald H Clements, Devin E Eckhoff, Phillipe Bouchard, Michael D George, William K Hu, Satya Dandekar, Phillip D Smith
  [show abstract] [hide abstract]
  ABSTRACT: Human intestinal macrophages contribute to tissue homeostasis in noninflamed mucosa through profound down-regulation of pro-inflammatory cytokine release. Here, we show that this down-regulation extends to Toll-like receptor (TLR)-induced cytokine release, as intestinal macrophages expressed TLR3-TLR9 but did not release cytokines in response to TLR-specific ligands. Likely contributing to this unique functional profile, intestinal macrophages expressed markedly down-regulated adapter proteins MyD88 and Toll interleukin receptor 1 domain-containing adapter-inducing interferon beta, which together mediate all TLR MyD88-dependent and -independent NF-kappaB signaling, did not phosphorylate NF-kappaB p65 or Smad-induced IkappaBalpha, and did not translocate NF-kappaB into the nucleus. Importantly, transforming growth factor-beta released from intestinal extracellular matrix (stroma) induced identical down-regulation in the NF-kappaB signaling and function of blood monocytes, the exclusive source of intestinal macrophages. Our findings implicate stromal transforming growth factor-beta-induced dysregulation of NF-kappaB proteins and Smad signaling in the differentiation of pro-inflammatory blood monocytes into noninflammatory intestinal macrophages.
  Journal of Biological Chemistry 04/2010; 285(25):19593-604. · 4.77 Impact Factor