A role for transient receptor potential vanilloid 4 in tonicity-induced neurogenic inflammation.

Background And Purpose: Changes in extracellular fluid osmolarity, which occur after tissue damage and disease, cause inflammation and maintain chronic inflammatory states by unknown mechanisms. Here, we investigated whether the osmosensitive channel, transient receptor potential vanilloid 4 (TRPV4), mediates inflammation to hypotonic stimuli by a neurogenic mechanism.

Experimental Approach: TRPV4 was localized in dorsal root ganglia (DRG) by immunofluorescence.

Triggering of proteinase-activated receptor 4 leads to joint pain and inflammation in mice.

Objective: To investigate the role of proteinase-activated receptor 4 (PAR-4) in mediating joint inflammation and pain in mice.

Methods: Knee joint blood flow, edema, and pain sensitivity (as induced by thermal and mechanical stimuli) were assessed in C57BL/6 mice following intraarticular injection of either the selective PAR-4 agonist AYPGKF-NH(2) or the inactive control peptide YAPGKF-NH(2). The mechanism of action of AYPGKF-NH(2) was examined by pretreatment of each mouse with either the PAR-4 antagonist pepducin P4pal-10 or the bradykinin antagonist HOE 140.

Intrathecal administration of proteinase-activated receptor-2 agonists produces hyperalgesia by exciting the cell bodies of primary sensory neurons.

Proteinase-activated receptors (PARs) are a family of G-protein-coupled receptors that are activated by endogenous serine proteinases that cleave the N-terminal domain of the receptor unmasking a "tethered ligand" sequence. Trypsin and other agonists at PAR(2) act on peripheral nerves to augment the transfer of nociceptive information. We tested whether PAR(2) agonists also exert a spinal pronociceptive effect by i.

Combined challenge of mice with Citrobacter rodentium and ionizing radiation promotes bacterial translocation.

Purpose: Both enteric infection and exposure to ionizing radiation are associated with increased intestinal permeability. However, the combined effect of irradiation and enteric infection has not been described. We combined infection of mice with the enteric pathogen, Citrobacter rodentium, with exposure to ionizing radiation and assessed the impact on colonic epithelial ion transport, permeability and bacterial translocation.

Citrobacter rodentium infection causes iNOS-independent intestinal epithelial dysfunction in mice.

Attaching-effacing bacteria are major causes of infectious diarrhea in humans worldwide. Citrobacter rodentium is an attaching-effacing enteric pathogen that causes transmissible murine colonic mucosal hyperplasia. We characterized colonic inflammation and ion transport at 3, 7, 10, 30, and 60 d after infection of C57Bl/6 mice with C.

Proteinase-activated receptor-1 is an anti-inflammatory signal for colitis mediated by a type 2 immune response.

Background: Activation of colonic proteinase activated receptor-1 (PAR1) provokes colonic inflammation and increases mucosal permeability in mice. The mechanism of inflammation is not neurogenic like in the paw of rats but depends on PAR1-mediated activation monocytic cells. PAR1 activation in the colon increases the release of lymphocyte T helper-1 (TH1) cytokines.

A major role for proteolytic activity and proteinase-activated receptor-2 in the pathogenesis of infectious colitis.

Citrobacter rodentium is a bacterial pathogen that causes a murine infectious colitis equivalent to enterohemorrhagic Escherichia coli infection in humans. Colonic luminal fluid from C. rodentium-infected mice, but not from sham-infected mice, contains active serine proteinases that can activate proteinase-activated receptor-2 (PAR2).

A role for proteinase-activated receptor-1 in inflammatory bowel diseases.

Proteinase-activated receptor-1 (PAR1), a G protein-coupled receptor activated by thrombin, is highly expressed in different cell types of the gastrointestinal tract. The activity of thrombin and of other proteinases is significantly increased in the colon of inflammatory bowel disease (IBD) patients. Since PAR1 activation in tissues other than the gut provoked inflammation, we hypothesized that PAR1 activation in the colon is involved in the pathogenesis of IBD.

Axonal atrophy in aging is associated with a decline in neurofilament gene expression.

Neurofilaments (Nfs) are major determinants of axonal caliber. Nf transcript levels increase during development and maturation, and are associated with an increase in Nf protein, Nf numbers, and caliber of axons. With aging there is axonal atrophy.