Inhibition of leukocyte migration into target organs has long been an attractive, though challenging, basis for anti-inflammatory strategies. However, to date, the manipulation of leukocyte rolling along blood vessels has not yielded successful new therapies. An important study may now open new avenues in this exciting field of anti-inflammatory therapies by introducing a putative inhibitor of poly-N-acetyllactosamine biosynthesis that affects selectin ligand activity and shows efficacy in a rodent skin inflammation model.
Thomas M. Zollner, Khusru Asadullah
The pathways between a receptor and transcriptional activation mediated by NF-κB are complex. The study of human gene mutations that result in dysregulation of these pathways has provided insight into the functions of individual components of the pathway, their interrelations, and the significance of these systems to the organism .
Jordan S. Orange, Raif S. Geha
Glycemic control is the primary mediator of diabetic microvascular complications and also contributes to macrovascular complications. A new study (see related article beginning on page 1049) reveals a previously unrecognized association between oxidant activation of poly(ADP ribose) polymerase (PARP) and upregulation of known mediators of glycemic injury. Inhibitors of PARP may have potential therapeutic roles in the prevention of diabetic complications.
Jane E.B. Reusch
Prevailing views concerning the pathogenic mechanisms of AIDS have shifted from models that focus primarily on direct HIV-mediated killing of CD4+ T cells to models that emphasize the pathogenic role of generalized immune system activation. The observation that increases in T cell turnover seen in HIV-infected individuals primarily reflect increased proliferation of effector-memory T cells supports the concept that chronic immune activation plays a prominent, if not predominant, role in the pathogenesis of AIDS.
Guido Silvestri, Mark B. Feinberg
Histone acetylation, regulated by two antagonistic enzymes — histone acetyltransferases (HATs) and histone deacetylases (HDACs) — results in transcriptional changes and also plays a critical role in cardiac development and disease. A new study shows that overexpression of the atypical transcriptional corepressor homeodomain-only protein (Hop) causes cardiac hypertrophy via recruitment of a class I HDAC. In contrast to the body of work on transcriptional mechanisms that drive cardiac hypertrophy, including class II HDACs, this report elucidates a novel growth-suppressing transcriptional pathway in cardiac muscle that opposes hypertrophic growth.
Yasuo Hamamori, Michael D. Schneider
Insulin-dependent diabetes mellitus is usually caused by the autoimmune destruction of pancreatic β cells by T cells. Methodologies to track the development, migration, and functional activation of one class of such T cells (CD4 T cells) have been limited. However, it now appears that this limitation has been overcome .
David V. Serreze, Edward H. Leiter
15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) affects gene transcription by activating PPARγ and by covalent addition to transcription factors and signaling molecules, However, it is not known whether the high concentrations of 15d-PGJ2 required for these responses are consistent with physiological levels. A new study suggests that in vivo 15d-PGJ2 levels are actually several orders of magnitude below the levels required to induce many of the biological effects attributed to this molecule.
William S. Powell
A novel circulation phosphaturic hormone is postulated to regulate systemic phosphate homeostasis. Two new studies reveal that the phosphaturic factor FGF-23 is increased in hypophosphatemic subjects with McCune-Albright syndrome and that secreted frizzled-related protein-4 (sFRP-4), a factor produced by tumors derived from subjects with tumor-induced osteomalacia, also has phosphaturic activity. It remains to be established whether FGF-23 and sFRP-4 represent two distinct phosphatonins or are somehow integrated in a novel phosphate-regulating bone-kidney axis.
L. Darryl Quarles
CD1d, a nonclassical MHC class I–like molecule, is prominently expressed on intestinal epithelial cells and is thought to function in the regulation of intestinal intraepithelial lymphocyte activity. Hsp110, an abundant heat shock protein present in essentially all mammalian tissues, has now been shown to upregulate CD1d expression in colonic tissue culture cell lines. Might this abundant chaperone serve an autocrine function in the regulation of CD1d expression?
Christopher V. Nicchitta
Mammals coexist in an overall symbiotic relationship with a complex array of commensal bacterial flora that colonizes the gastrointestinal tract. These intestinal bacteria interface with cells of the mucosal immune system, including DCs. Here we discuss mechanisms of interaction between intestinal bacteria and DCs and the role of localized gastrointestinal immune responses.
Holm H. Uhlig, Fiona Powrie
No posts were found with this tag.