Toll-like receptors (TLRs) recognize microbial molecular signatures and can initiate innate immune responses against invading pathogens. A new study reports how TLR2 expression by endothelia is locally upregulated by the action of activated polymorphonuclear neutrophils via an unprecedented mechanism involving cell-cell interaction and NAD(P)H oxidase. The report reveals yet another way in which the primordial innate immune system is remarkably complex.
Eicke Latz, Douglas T. Golenbock
Uroguanylin is a peptide hormone that regulates sodium excretion by the kidney when excess NaCl is consumed. A new study demonstrates that mice deficient in uroguanylin have blunted urinary sodium excretion responses to oral sodium loads in addition to elevated blood pressure (see related article beginning on page 1244). A physiological role for uroguanylin is discussed, linking the intestine and kidney in an endocrine axis for the maintenance of sodium balance.
Leonard R. Forte
Stat3 is a vital transcription factor that is activated downstream of the gp130 receptor, primarily via IL-6 signaling in adult liver. A new study demonstrates that Stat3 provides hepatoprotection against Fas-mediated apoptotic liver damage by two mechanisms: direct inactivation of caspases and reduction of reactive oxygen species.
Rebecca Taub
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
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