IL-17 is overproduced by T cells from the peripheral blood and fibrotic lesions of the skin and lungs in SSc patients. These results suggest that IL-17 overproduction plays an important role in the pathogenesis of SSc, especially in the early stages of the disease, by inducing the proliferation of fibroblasts and the production of IL-1 and the expression of adhesion molecules on endothelial cells.

SummaryWe have previously shown that antigen-induced eosinophil recruitment into the tissue of sensitized mice is mediated by CD4 + T cells and interleukin 5. To determine whether interferon 3' ) regulates antigen-induced eosinophll recruitment into the tissue, we studied the effect of recombinant (r) murine IFN-3, and of anti-IFN-3, monoclonal antibody (mAb) on the eosinophil infiltration of the trachea induced by antigen inhalation in mice. The intraperitoneal administration of rlFN-3, prevented antigen-induced eosinophil infiltration in the trachea of sensitized mice. The administration of rIFN-3, also decreased antigen-induced CD4 + T cell but not CD8 + T cell infiltration in the trachea. On the other hand, pretreatment with anti-IFN-'y mAb enhanced antigen-induced eosinophil and CD4 + T cell infiltration in the trachea. These results indicate that IFN-3, regulates antigen-induced eosinophil recruitment into the tissue by inhibiting CD4 + T cell infiltration. Eosinophil infiltrate is a characteristic feature of allergic inflammation such as asthma. In a murine model of airway late-phase reaction, we have previously shown that antigeninduced eosinophil recruitment into the tissue of sensitized mice is mediated by CD4 + T cells and IL-5 (1). However, the mechanism that regulates antigen-induced eosinophil recruitment into the tissue is unknown. It has been suggested that CD4 + Th cells can be divided into two subsets (Thl and Th2 cells) on the basis of their different patterns of cytokine secretion (2); Thl cells produce Ib2, IFN-3,, and lymphotoxin, and Th2 cells produce Ib4, IL-5, and Ib6. Furthermore, IFN-3, has been shown to be a major regulatory cytokine that inhibits the proliferation of Th2 cells in vitro (3, 4) and antagonizes the in vivo Th2-type responses such as IL-4-dependent IgE antibody production (5). Therefore, to determine whether IFN-3, regulates antigen-induced eosinophil recruitment into the tissue, we studied the effect of recombinant murine IFN-3' and of anti-IFN-3, mAb on the eosinophil infiltration of the trachea induced by antigen inhalation in mice. Our results indicate that IFN-3, regulates antigen-induced eosinophil recruitment into the tissue by inhibiting CD4 § T cell infiltration. Materials and Methods Mice and Immunization. 8-wk-old BALB/c mice (Charles RiverLaboratories, Shizuoka, Japan) were immunized intraperitoneally twice with 1 #g of OVA (Sigma Chemical Co., St. Louis, MO) in 4 mg of aluminum hydroxide at a 2-wk interval. 10-14 d after the second immunization, the sensitized mice were challenged with aerosolized OVA as described below. Antigen-induced Eosinophil lnfihration in Mouse Trachea.The eosinophil infiltration into the trachea was induced by the inhalation of antigen in sensitized mice, and the number of eosinophils infiltrating into the submucosal tissue of trachea was evaluated as described previously (1). Briefly, the sensitized mice inhaled aerosolized OVA (50 mg/ml) dissolved in 0.9% saline by a nebulizer (646; DeVilbiss Corp., Somerset, PA) for 20 min. As a...

The LG4 module of the laminin ␣3 chain (␣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. LG4 is mediated through the IL-1␤ autocrine loop in keratinocytes but the mechanism of the induction in fibroblasts is different. Our study suggests that the laminin ␣3 LG4 module may play an important role in tissue remodeling by inducing MMP-1 expression during wound healing.Laminin is a heterotrimeric glycoprotein specific to the basement membrane and has many biological functions, including cell adhesion, migration, cell proliferation, differentiation, angiogenesis, and tumor invasion (for reviews, see Refs. 1 and 2). At least 15 laminin isoforms (laminin-1 to -15) have been identified with 11 genetically distinct chains: 5 ␣ chains, 3 ␤ chains, and 3 ␥ chains. Three chains assemble into a cross-shaped heterotrimer (␣␤␥) through coiled-coil interaction at the long arm of the cross (3, 4). Laminin-5 is specific to epithelial cells and a component of the anchoring filament. Laminin-5 forms a complex with the hemidesmosome apparatus by interacting with laminin-6 and -7, collagen VII (5, 6), and fibulin-1 and -2 (7, 8). Laminin-5 consists of the ␣3, ␤3, and ␥2 chains. The ␣3 chain contains a large globular module (G module) 1 at the C terminus, which consists of a tandem repeat of five homologous LG modules (LG1-LG5), each module containing about 200 amino acid residues autonomous folding unit (9). The LG subdomains of laminin ␣ chains have been shown to bind heparin, ␣ 3 ␤ 1 , ␣ 6 ␤ 4 integrins, ␣-dystroglycan, and syndecan (Ref. 10; for review, see Ref. 11) and are implicated as active regions for various biological functions.Syndecans, cell surface heparan sulfate proteoglycans, have been shown to bind the G module of laminin ␣ chains and are involved in laminin-mediated biological functions. We previously demonstrated that keratinocytes and fibroblasts bound LG4 of the ␣3 G module via syndecans (12). Neurite outgrowth of PC12 cells was induced by ␣3 LG4 via syndecans (13). We also showed that HT1080 cells bound to the C-terminal G module of the laminin ␣4 chain through syndecans (14). The interaction of laminin ␣1 LG4 and syndecan family or heparan sulfate proteoglycans was essential for embryonic basement membrane assembly (15).Although laminin ␣3 LG4 -5 is processed in the keratinocyte culture medium (16,17), the unprocessed laminin ␣3 chain was found in a cell layer of the provisional edge of the cell sheet in cultured keratinocytes. In vivo, the unprocessed ␣3 chain has been identified especially in the newly synthesized epidermal basement membrane in wounds but disappears from the mature basement membrane (Refs. 18 and 19; for review, see Ref. 20).Matrix metalloproteinase-1 (MMP-1) is expressed in the basal keratinocytes at the leading edge of re-epithelization (Refs. 21 and 22; for review, see Ref. 23). At the wound edge, MMP-1 degrades collage...

Our results showed that nectin-1alpha is located at cell-cell adherens junctions in human skin and that reduction of nectin-1alpha at cell-cell adherens junctions may be involved in the invasion of squamous cell tumours.

Keratin 9 mutation was examined in a Japanese kindred of epidermolytic palmoplantar keratoderma (EPPK), which is a dominantly inherited autosomal disorder of keratinization characterized by diffuse thickening of the palms and soles and by epidermolytic hyperkeratosis histologically. We report herein a novel mutation, a C --> G transversion at nucleotide position 541 that converts a leucine residue (CTC) to a valine (GTC) at codon 159. As in all other reported cases of keratin 9 mutation in EPPK, this mutation lies within the highly conserved coil 1A of the rod domain, which is considered to play a role in the correct alignment of the coiled-coil molecules.