A Splice Switch in SIGIRR Causes a Defect of IL-37-Dependent Anti-Inflammatory Activity in Cystic Fibrosis Airway Epithelial Cells.

Cystic fibrosis (CF) is a hereditary disease typically characterized by infection-associated chronic lung inflammation. The persistent activation of toll-like receptor (TLR) signals is considered one of the mechanisms for the CF hyperinflammatory phenotype; however, how negative regulatory signals of TLRs associate with CF inflammation is still elusive. Here, we showed that the cell surface expression of a single immunoglobulin interleukin-1 receptor (IL-1R)-related molecule (SIGIRR), a membrane protein essential for suppressing TLRs- and IL-1R-dependent signals, was remarkably decreased in CF airway epithelial cells compared to non-CF cells.

Different effects on the tonus of colon and ileum isolated from mouse by resin glycoside (pharbitin) of Pharbitidis Semen.

Background: Pharbitidis Semen (the seeds of Pharbitis nil), traditionally used as a purgative in Japan, China and Korea, contains a resin glycoside fraction named pharbitin, which is known as a purgative ingredient. Due to the complex nature of pharbitin, little is known about either the action on intestinal tension caused by resin glycoside itself or by its components.

Methods: In this study, we investigated the effects of pharbitin, the glycosidic acid fraction (pharbitic acid) and the aglycone fraction (phar-genin) generated from pharbitin on peristalsis of colon and ileum isolated from mice with the Magnus method.

Lipopolysaccharide decreases single immunoglobulin interleukin-1 receptor-related molecule (SIGIRR) expression by suppressing specificity protein 1 (Sp1) via the Toll-like receptor 4 (TLR4)-p38 pathway in monocytes and neutrophils.

Single immunoglobulin interleukin-1 receptor-related molecule (SIGIRR) is one of the immunoglobulin-like membrane proteins that is crucial for negative regulation of toll-like receptor 4 (TLR4) and interleukin-1 receptor. Despite the importance of understanding its expression and function, knowledge is limited on the regulatory mechanism in the epithelial tissues, such as the liver, lung, and gut, where its predominant expression is originally described. Here, we found expression of SIGIRR in non-epithelial innate immune cells, including primary peripheral blood monocytes, polymorphonuclear neutrophils, monocytic RAW264 cells, and neutrophilic-differentiated HL-60 cells.

Identification of the occipito-pontine tract using diffusion-tensor fiber tracking in adult-onset adrenoleukodystrophy with topographic disorientation.

X-linked adrenoleukodystrophy is a severe and progressive neurodegenerative disease caused by the peroxisomal transporter ATP-binding cassette, subfamily D, member 1 gene mutations. The defect of this gene product results in accumulation of very-long-chain fatty acids in organs and serum, central demyelination, and peripheral axonopathy. Although there are different magnetic resonance (MR) findings which reflect various phenotypes in adrenoleukodystrophy, some cases present with specific symmetrical occipital white-matter lesions.

Alpha1-acid glycoprotein suppresses rat acute inflammatory paw edema through the inhibition of neutrophils activation and prostaglandin E2 generation.

Alpha(1)-acid glycoprotein (AGP) is an acute phase protein. Whereas the expression of AGP in an inflammatory state is enhanced by inflammatory cytokines including interleukin-1, 6 (IL-1 and IL-6), and tumor necrosis factor-alpha (TNF-alpha), the biological significance of AGP remains unclear. In the current study, the anti-inflammatory effect of AGP on the acute inflammatory state was examined in vivo and in vitro.

[Drug-induced anomalous contraction of gastrointestinal tract of mice with impaired c-kit function].

Drug-induced contraction of gastrointestinal tracts seems to depend upon the extent of their rhythmic contraction that is driven by the activity of gastrointestinal pacemaker cells. In BALB/c mice chronically administrated with a neutralizing anti-c-Kit monoclonal antibody (ACK2), rhythmic contraction of the gastrointestinal tract was impaired and contractile responses to drugs, including acetylcholine, prostaglandin F(2alpha), and bradykinin, were anomalously augmented. Histochemical analysis of the c-kit-positive cells in the gastrointestinal tract revealed the decreased number of c-kit-positive cells in the ACK2-treated animals, which lead to the impaired rhythmic contraction.

Effects of alpha(1)-acid glycoprotein on isometric tension of mouse aorta.

We examined the effects of human alpha(1)-acid glycoprotein on isometric tension of mouse aortic rings. alpha(1)-Acid glycoprotein (7.5-75 microM) produced a transient, concentration-dependent relaxation of the phenylephrine-precontracted preparation.

[Genetic basis of autonomic gastrointestinal motility and pathophysiological models].

The origin of rhythmicity in gastrointestinal motility was long thought to involve the activity of interstitial cells of Cajal (ICC) that locate in close association with enteric neurons and smooth muscle cells. We have demonstrated that significant decrease in the number of cells immunopositive to c-Kit, a type of tyrosine kinase receptor, in the gastrointestinal tract of mice mutated at the W/c-kit locus and BALB/c mice administered with neutralizing c-Kit antibody leads to the impaired autonomic motility of the gastrointestinal tract. It is also demonstrated that ICC express c-kit which plays important roles in development and maintenance of the ICC network in the gastrointestinal tract.