The effect of calprotectin on TSLP and IL-25 production from airway epithelial cells

Background: Calprotectin is a heterodimer complex of the S100A8 and S100A9 proteins, and has various functions as an innate mediator at the sites of inflammation. The aim of this study was to elucidate the roles of calprotectin in the eosinophilic chronic rhinosinusitis (ECRS). Methods: Allergen-induced production of calprotectin was evaluated in cultured normal human bronchial epithelial (NHBE) cells by ELISA and RT-PCR. We then examined the roles of calprotectin on Alternaria alternata (Alternaria)-induced production of thymic stromal lymphopoietin (TSLP) and IL-25 in NHBE cells. The extracellular concentration and allergen-induced secretion of calprotectin in cultured primary nasal epithelial (PNE) cells were examined and compared between patients with ECRS and non-eosinophilic chronic rhinosinusitis (NECRS). Results: Alternaria, house dust mites, protease from Staphylococcus aureus, papain, trypsin, polyinosinic:polycytidylic acid and lipopolysaccharide stimulated calprotectin production in the cultured NHBE cells. The combination of calprotectin and ATP stimulated the production of TSLP and IL-25 in NHBE cells, and calprotectin stimulated Alternaria-induced production of TSLP and IL-25, which was suppressed by blocking P2 purinergic receptors and by treatment with siRNA for S100A8, S100A9 or calprotectin receptors (Toll-like receptor 4 or receptor for advanced glycation end products). Allergen-induced calprotectin production was significantly stimulated in PNE cells from patients with ECRS. Conclusions: These results indicate that calprotectin enhances the allergen-induced Th2-type inflammatory responses in airway epithelial cells via the secretion of TSLP and IL-25, and that calprotectin secreted by the epithelial cells may be involved in the pathogenesis of ECRS

M1/M2 Macrophage Skewing is Related to Reduction in Types I, V, and VI Collagens with Aging in Sun-Exposed Human Skin

Sun-exposed, aged human skin is fragile because of collagen fragmentation and loss. We recently reported that the balance of M1 and M2 macrophages is associated with chronic inflammation and related inflammaging in sun-exposed human skin. In this study, we analyzed its role in the maintenance of collagen matrix formation by performing histological analyses of human facial skin. In addition, RNA sequencing, protein assays, and functional assays revealed the details of the mechanism. The number of M2 macrophages was positively correlated with the abundance of type I collagen, whereas the M1/M2 ratio was negatively correlated with the abundance of type V and VI collagen, which are the essential minor collagens required for collagen assembly in the skin; however, there was no correlation with type III collagen. Furthermore, M2 macrophages induced the expression of the proteins required for the assembly of collagen fibrils, suggesting that the M1/M2 balance controls not only the quantity but also the quality of the collagen matrix. Indeed, M1 macrophages induced abnormal collagen fibrils consisting of types I, V, and VI collagens. Our results demonstrate the relationship between the M1/M2 balance and the dysregulation of collagen homeostasis in photoaged skin and suggest the possible involvement of macrophages in skin photoaging

Impaired immunosuppressive response to ultraviolet radiation in interleukin-10-deficient mice

Exposure to mid-range ultraviolet radiation (UVR) [280 – 320 nm, ultraviolet B (UVB) radiation] inhibits the acquisition of delayed-type hypersensitivity in mice and contact hypersensitivity in rodents and humans. Intraperiotoneal administration of interleukin 10 (IL-10) inhibits the sensitization of mice to alloantigens for a delayed-type hypersensitivity reaction and administration of neutralizing antibodies to IL-10 largely, but not totally, blocks the UVR-mediated suppression of the ability to sensitize mice. This suggests that these inhibitory effects of UVB radiation may be mediated by release of IL-10. To test this hypothesis directly, IL-10 gene-targeted (IL-10T) mice lacking expression of IL-10 were examined for the ability of UVB radiation to suppress induction of delayed-type hypersensitivity to alloantigens. IL-10T mice were completely resistant to UVB-induced immunosuppression in this system. Interestingly, UVB radiation could suppress in IL-10T mice the induction of contact hypersensitivity to a hapten applied to the skin at a site distant of irradiation, supporting the concept that regulation pathways of delayed-type hypersensitivity and contact hypersensitivity responses by UVR differ. These data provide additional understanding of the mechanisms of immunosupression induced by UVR and suggest that IL-10 release subsequent to UVB radiation may play a role in the growth of immunogenic UVB-induced cutaneous malignancies in the primary host

Differential Regulation of Epidermal Cell Tumor-Antigen Presentation by IL-1α and IL-1β

IL-1 exists in two forms, termed IL-1α and IL-1β, which exert similar effects in a number of biologic models. Recently, there have been reports of some differences in the activities of these two species in some systems. To address this issue with regard to Langerhans cells, Langerhans cell-enriched preparations of epidermal cells were treated with either IL-1α or IL-1β before pulsing with S1509a tumor-associated antigens and subsequent use for immunization of naïve mice to S1509a. While epidermal cells treated with 100 U IL-1β per ml were able to induce protective tumor immunity (as indicated by the rejection of a subsequent tumor challenge with viable S1509a tumor cells), epidermal cells treated with 100 U IL-1α per ml failed to confer protective immunity. At 1000 U per ml, IL-1β also inhibited the ability of epidermal cells to induce tumor immunity. To investigate the effects of the two IL-1 forms on elicitation of tumor immunity, naïve mice were immunized against the S1509a tumor by s.c. injection of dead S1509a cells. Epidermal cells enriched for Langerhans cells were treated with either 100 U IL-1α or IL-1β per ml before tumor-associated antigens-pulsing. Epidermal cells were then washed and injected into a hind footpad of tumor immune mice and 24 h footpad swelling was assessed as a measure of delayed-type hypersensitivity. Exposure to IL-1α led to suppressed elicitation of delayed-type hypersensitivity, whereas IL-1β treated epidermal cells elicited a normal (100 U per ml) or enhanced (1000 U per ml) level of delayed-type hypersensitivity. Previous experiments indicated that the suppressive effects of IL-1α on induction of immunity may be mediated by TNFα. Therefore, the ability of IL-1α or IL-1β to induce epidermal cell production of TNFα was assessed. IL-1α induced epidermal cells to secrete significantly higher amounts of TNFα protein compared with stimulation with IL-1β. IL-1α and IL-1β appear to differentially regulate epidermal cell antigen presenting capability

Reduction of Cedar Pollen Adhesion by Lecithin Polymer Coating

Background: Avoidance of allergens is one of the most effective treatments of allergenic diseases, including pollinosis. Although various masks and goggles for pollinosis sufferers are commercially available, little work has been done on preventing adhesion of pollen to the human body and clothes. We have examined the effect of polymer coating on adhesion of cedar pollen to skin, hair and fabrics, and found that a lecithin polymer (LP), containing both cationic and anionic sites, is highly effective in reducing adhesion levels. Methods: We evaluated the changes in electrostatic charge and frictional coefficient of sample surfaces after coating with an anionic polymer (AP), a cationic polymer (CP), a nonionic polymer (NIP), or LP (each applied by spraying 0.10% polymer solution in ethanol/water). Pollen adhesion level was evaluated by observation of the number of cedar pollen particles on video microscope (VMS) images and by quantification of cedar pollen antigen Cry j1 with a sandwich ELISA system. Adhesion of pollen to human skin or hair was also examined by VMS observation. Results: LP-coated samples showed a significant reduction in electrostatic charge level and frictional coefficient. We presumed that these properties are closely related to the significant reduction in the adhesion level of cedar pollen or Cry j1 compared with CP, AP or NIP-coated samples. A similar effect was seen on LP-treated skin, and LP-treated waxed hair. Conclusions: Our results suggest that coating with LP could help in the management of pollinosis by reducing the contact level of patients with cedar pollen antigens

Synchronous bilateral lung adenocarcinomas associated with vulvar rhabdomyosarcoma in a 15-year-old girl

Pediatric malignancies are thought to be risk factors of second malignant neoplasms. However, lung cancer associated with rhabdomyosarcoma is extremely rare. When multiple pulmonary lesions are observed in cancer patients, resection is necessary to distinguish them from metastatic lesions. We report an extremely rare case of synchronous bilateral multiple lung cancers showing ground glass nodules (GGNs) associated with rhabdomyosarcoma in a 15-year-old girl with vulvar rhabdomyosarcoma. When we identify GGNs in adolescents with a history of rhabdomyosarcoma, we should consider lung cancer as a differential diagnosis in addition to pulmonary metastasis usually showing solid nodule. In the present case with tiny lesions, surgical resection using lipiodol-marking helped to ensure both an early diagnosis and curative treatment. Keywords: Synchronous bilateral multiple lung cancers, Adolescent, Rhabdomyosarcom