Hypertension increases mechanical force on the arterial wall by as much as 30%, resulting in marked alterations in signal transductions and gene expression in vascular smooth muscle cells (VSMCs) that contribute to matrix protein synthesis, cell proliferation, and differentiation. How the mechanical stimuli are converted into a biological signal in cells has yet to be studied. We investigated t...

The LG4 module of the laminin alpha 3 chain (alpha 3 LG4), a component of epithelial-specific laminin-5, has cell attachment activity and binds syndecan (Utani, A., Nomizu, M., Matsuura, H., Kato, K., Kobayashi, T., Takeda, U., Aota, S., Nielsen, P. K., and Shinkai, H. (2001) J. Biol. Chem. 276, 28779-28788). Here, we show that recombinant alpha 3 LG4 and a 19-mer synthetic peptide (A3G756) wit...

Prazosin, an antagonist of alpha 1-adrenergic receptors, has been found to suppress the clinical and histological expression of experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. Suppression was more significant in females than in males and was a dose-dependent phenomenon. Analysis of the effect of other adrenergic receptor antagonists supports the conclusion that the suppressive...

The goals of this study were to develop compounds that were selective and highly efficacious agonists at alpha-7 receptors, while varying in antagonist activity; and to test the hypothesis that these compounds had memory-related and neuroprotective actions associated with both agonist and antagonist alpha-7 receptor activities. Three compounds were identified; E,E-3-(cinnamylidene)anabaseine (3...

CC chemokines constitute a novel class of cytokines that attract and activate monocytes and lymphocytes, as well as basophil and eosinophil leukocytes, with distinct target cell profiles, and are believed to be involved in the regulation of different types of inflammation. The action of the recently identified monocyte chemotactic protein 3 (MCP-3) on human basophil and eosinophil function was ...

The cellular and molecular mechanisms governing bradykinin B1 and B2 receptor expression and function are poorly understood. We investigated the regulation of both B1 and B2 receptors in human embryonic lung fibroblasts (HEL 299) by the proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta). TNF-alpha and IL-1beta both induced a rapid and transient in...

Human alpha-thrombin was a chemoattractant for human neutrophils yielding a maximal response of similar magnitude to that observed with formyl-Met-Leu-Phe. The observed chemotaxis was not due to stimulation of the proteolytically activated thrombin receptor since: (1) this receptor was not detected by flow cytometry; (2) the inactive thrombin mutant Ser195-->Ala elicited a chemotactic response ...

Recently, the family of mammalian genes homologous to that for the low density lipoprotein (LDL) receptor has grown. One of the new family members, termed LDL receptor-related protein/alpha 2-macroglobulin receptor (LRP/alpha 2MR), is one of the largest cell surface proteins characterized to date. Its functions have been hypothesized to include the plasma clearance of chylomicron remnants and a...

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of the nuclear receptor (NR) superfamily of ligand-activated transcriptional factors. Among other functions, PPAR-gamma acts as a key regulator of the adipogenesis. Since several cytokines (IL-1, TNF-alpha, TGF-beta) had been known to inhibit adipocyte differentiation in mesenchymal stem cells (MSCs), we examined the effe...

A human receptor that is selective for the CXC chemokines IP10 and Mig was cloned and characterized. The receptor cDNA has an open reading frame of 1104-bp encoding a protein of 368 amino acids with a molecular mass of 40,659 dalton. The sequence includes seven putative transmembrane segments characteristic of G-protein coupled receptors. It shares 40.9 and 40.3% identical amino acids with the ...