We recently identified a series of transforming growth factor--responsive genes in A549 human adenocarcinoma cell line by a gene trap screening method. Here we report the molecular cloning and characterization of one of these genes, designated TMX, that encodes a novel protein of 280 amino acid residues. The TMX protein possesses an N-terminal signal peptide followed by one thioredoxin (Trx)-like domain with a unique active site sequence, Cys-Pro-Ala-Cys, and a potential transmembrane domain. There are putative TMX homologs with identical active site sequences in the Caenorhabditis elegans and Drosophila genomes. Using recombinant proteins expressed in Escherichia coli, we demonstrated the activity of the Trx domain of TMX to cleave the interchain disulfide bridges in insulin in vitro. The TMX transcript is widely expressed in normal human tissues, and subcellular fractionation and immunostaining for an epitope-tagged TMX protein suggest that TMX is predominantly localized in the endoplasmic reticulum (ER). When TMX was expressed in HEK293 cells, it significantly suppressed the apoptosis induced by brefeldin A, an inhibitor of ER-Golgi transport. This activity was abolished when two Cys residues in the active site sequence were mutated to Ser, suggesting that the Trxlike activity of TMX may help relieve ER stress caused by brefeldin A.
We investigated the effects of a single dose of mouse interleukin-31 (IL-31) on scratching behaviour in comparison with spontaneous skin-lesion- or serotonin (5-HT)- induced scratching behaviour in NC/Nga and BALB/c mice. Intradermal (i.d.) injection of IL-31 caused a gradual increase in long-lasting scratching (LLS, over 1.5 s) about 3 h after administration followed by a gradual decrease for over 24 h after administration. I.d. injection of IL-31 significantly increased the total LLS counts/24 h but not short-lasting scratching (SLS, 0.3-1.5 s). In skin-lesioned NC/Nga mice, the LLS but not SLS counts were significantly higher than those in non-skin-lesioned NC/Nga mice. We also investigated 5-HT-induced scratching in BALB/c mice, SLS but not LLS increased immediately after the injection and then decreased to baseline after at 20 min. These results suggest that IL-31 may participate in the sensation of itching and promote scratching behaviour in skin-lesioned NC/Nga mice, an animal model of atopic dermatitis (AD).
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