We wish to correct some errors that we inadvertently introduced in revising and editing our recent Commentary. In the text, we incorrectly cited (Wolburg et al., 2003) in reference to the downregulation of claudin-23 in gastric cancer; the reference should be (Katoh and Katoh, 2003) as correctly cited in Table 3. (Peacock et al., 1997) was mistakenly inserted in relation to the discussion of the number of claudin genes. We also wrote the number of human claudin genes as 24, the number currently ascribed to the mouse claudin genes (GenBank). The correct number ascribed to human claudin genes by (Katoh and Katoh, 2003) is 23, up from the originally predicted 20 (Venter et al., 2001). In this regard, it is worth noting that, since our Commentary was published, (Loh et al., 2004) have annotated the claudins in the teleost Fugu rubripes genome and reported 56 claudin genes, of which only 35 can be assigned orthology to 17 mammalian claudin genes, with the remaining 21 being specific to the fish lineage and most of the 56 expressed in a more or less tissue-specific fashion, or at particular developmental stages. This, along with other issues we raised, suggests that additional annotation of multiple other genomes and other functional genomics approaches will be useful to advance our understanding of claudin biology and physiology. Finally, based on a Clustal analysis of full-length claudins, we reported that there is a highly conserved WWCC motif of unknown function within the first loop of the claudins analysed; a motif also reported in alignments of claudins carried out by (Katoh and Katoh, 2003). IntroductionIn multicellular organisms, certain tissues must be separated from each other and protected against the external environment. Epithelial and endothelial sheets achieve this by providing cellular borders that cover external and internal surfaces throughout the body. Complexes between adjacent cells in these sheets include gap junctions, desmosomes, adherence junctions and tight junctions (TJs) -also known as the zonula occludens. Early ultrastructural and morphological data revealed TJs as continuous circumferential intercellular contacts between epithelial cells (Farquhar and Palade, 1963) that create a barrier to the paracellular movement of water, solutes and immune cells (Madara, 1998;Nusrat et al., 2000). Later work showed that this epithelial barrier is heterogeneous in tightness and dynamics depending on the tissue. In addition it is physiologically regulated, and its disruption contributes to human disease. Numerous in-depth reviews on TJs exist (Begley and Brightman, 2003;Fanning et al., 1999; GonzalezMariscal et al., 2003;Heiskala et al., 2001;Madara, 1989;Mitic and Anderson, 1998;Stevenson, 1999;Tsukita and Furuse, 2000a;Tsukita and Furuse, 2000b;Tsukita et al., 2001;Zahraoui et al., 2000). Here we therefore only briefly summarize their essential features and then focus on the recent identification of claudins and our evolving understanding of their contribution to TJ structure and function. Tight...

Abstract. Keratin 5 and keratin 14 have been touted as the hallmarks of the basal keratin networks of all stratified squamous epithelia. Absence of K14 gives rise to epidermolysis bullosa simplex, a human blistering skin disorder involving cytolysis in the basal layer of epidermis. To address the puzzling question of why this disease is primarily manifested in skin rather than other stratified squamous epithelia, we ablated the K14 gene in mice and examined various tissues expressing this gene. We show that a key factor is the presence of another keratin, K15, which was hitherto unappreciated as a basal cell component. We show that the levels of K15 relative to K14 vary dramatically among stratified squamous epithelial tissues, and with neonatal development. In the absence of K14, K15 makes a bona fide, but ultrastructurally distinct, keratin filament network with K5. In the epidermis of neonatal mutant mice, K15 levels are low and do not compensate for the loss of K14. In contrast, the esophagus is unaffected in the neonatal mutant mice, but does appear to be fragile in the adult. Parallel to this phenomenon is that esophageal K14 is expressed at extremely low levels in the neonate, but rises in postnatal development. Finally, despite previous conclusions that the formation of suprabasal keratin filaments might depend upon K5/K14, we find that a wide variety of suprabasal networks composed of different keratins can form in the absence of K14 in the basal layer.

Interleukin 6 (IL-6) is a cytokine that mediates a wide range of inflammatory and Immune responses. Its expression is elevated in inflammatory or immunodeficient dise, including psoriasis, rheumatoid arthritis, and AIDS.