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Periostin is a matricellular protein as well as an extracellular matrix (ECM) protein belonging to the fasciclin family. Periostin plays important roles as a matricellular protein in the setting of allergic diseases by binding to several integrins on various cells. Since periostin is induced mainly by IL‐4 and IL‐13, signature type 2 cytokines, and it is highly expressed in the subepithelial regions of many chronic allergic diseases, periostin has emerged as a novel biomarker reflecting type 2 inflammation in allergic diseases. It has, moreover, been revealed that periostin has characteristics different from other type 2 biomarkers such as eosinophil count and fractional exhaled nitric oxide (FeNO), reflecting fibrosis or tissue remodeling. From this, we may say that serum periostin is a "chronic" type 2 biomarker, whereas FeNO and possibly the eosinophil count are "acute" type 2 biomarkers. In contrast, it is still uncertain how we can apply periostin measurement to the use of biologics for allergic diseases. By examining the roles of periostin in allergy and the utility and potential of periostin in developing diagnostics against allergic diseases, it is hoped that in the near future, we can develop a new strategy to treat allergic patients. [ABSTRACT FROM AUTHOR]

Objective: Periostin, a matricellular protein, is produced from airway epithelial cells and lung fibroblasts by IL-13. It has been suggested that periostin is involved in allergic inflammation and fibrosis. However, the usefulness of serum periostin measurement in the assessment of airway inflammation and remodeling and management of asthmatic patients is still debated. We aimed to determine whether serum periostin levels reflect eosinophilic airway inflammation and airway remodeling in asthma. Methods: We examined the relationship of serum periostin levels with clinical features, biomarkers for eosinophilic airway inflammation, fraction of exhaled nitric oxide (FeNO) levels and blood eosinophil counts, and pulmonary functions in 235 well-controlled asthmatic patients on inhaled corticosteroids (ICS) treatment. Results: Serum periostin levels were positively correlated with blood eosinophil counts (%) and age (r = 0.36 and 0.23, respectively), and were negatively correlated with body weight and FEV1/FVC (%) (r = −0.24 and − 0.23, respectively) in well-controlled asthmatic patients on ICS treatment (daily dose of 453 µg equivalent to fluticasone propionate). Blood eosinophil counts and serum periostin levels were similarly associated with increased FeNO levels (≥40 ppb) in the asthmatics. Serum periostin levels were better associated with fixed airflow limitation (FEV1/FVC ratio <70%) than FeNO levels, blood eosinophil counts or total IgE levels in the asthmatics. Multivariate analysis showed that fixed airflow limitation was significantly associated with high serum periostin levels (≥97 ng/ml) (Odds ratio 3.2). Conclusions: Serum periostin levels serve as a biomarker for both eosinophilic airway inflammation and fixed airflow limitation in well-controlled asthmatics on ICS treatment. [ABSTRACT FROM AUTHOR]

Summary: Background: Some asthmatics develop irreversible chronic airflow obstruction, for example, fixed airflow obstruction (fixed‐AO). This is probably a consequence of airway remodelling, but neither its relation to inflammation nor which asthma biomarkers can be clinically useful are elucidated. We hypothesized that the presence of type 2 inflammation relates to fixed‐AO. Objectives: To evaluate the presence of four markers for type 2 inflammation in fixed airflow obstruction among asthmatics. Methods: This was a cross‐sectional study of 403 participants with asthma, aged 17‐75 years, from three Swedish centres. Fixed airflow obstruction was defined as forced expiratory volume during the first second (FEV1) over forced vital capacity (FVC) being below the lower limit of normal (LLN). The following type 2 inflammation markers were assessed: exhaled nitric oxide (FeNO), serum periostin, serum eosinophil cationic protein (S‐ECP), and urinary eosinophil‐derived neurotoxin (U‐EDN). Results: Elevated U‐EDN (values in the highest tertile, ≥65.95 mg/mol creatinine) was more common in subjects with fixed‐AO vs. subjects without fixed‐AO: 55% vs. 29%, P < 0.001. Elevated U‐EDN related to increased likelihood of having fixed‐AO in both all subjects and never‐smoking subjects, with adjusted (adjusted for sex, age group, use of inhaled corticosteroids last week, atopy, early‐onset asthma, smoking history, and packyears) odds ratios (aOR) of 2.38 (1.28‐4.41) and 2.51 (1.04‐6.07), respectively. In a separate analysis, having both elevated S‐ECP (>20 μg/L) and U‐EDN was related to having the highest likelihood of fixed‐AO (aOR (95% CI) 6.06 (2.32‐15.75)). Elevated serum periostin or FeNO did not relate to fixed‐AO. Conclusions and clinical relevance: These findings support that type 2 inflammation, and in particular eosinophil inflammation, is found in asthma with fixed‐AO. This could indicate a benefit from eosinophil‐directed therapies. Further longitudinal studies are warranted to investigate causality and relation to lung function decline. [ABSTRACT FROM AUTHOR]

We found for the first time that IL-4 and IL-13, signature type 2 cytokines, are able to induce periostin expression. We and others have subsequently shown that periostin is highly expressed in chronic inflammatory diseases-asthma, atopic dermatitis, eosinophilc chronic sinusitis/chronic rhinosinusitis with nasal polyp, and allergic conjunctivitis-and that periostin plays important roles in the pathogenesis of these diseases. The epithelial/mesenchymal interaction via periostin is important for the onset of allergic inflammation, in which periostin derived from fibroblasts acts on epithelial cells or fibroblasts, activating their NF-κB. Moreover, the immune cell/non-immune cell interaction via periostin may be also involved. Now the significance of periostin has been expanded into other inflammatory or fibrotic diseases such as scleroderma and pulmonary fibrosis. The cross-talk of periostin with TGF-β or pro-inflammatory cytokines is important for the underlying mechanism of these diseases. Because of its pathogenic importance and broad expression, diagnostics or therapeutic drugs can be potentially developed to target periostin as a means of treating these diseases. [ABSTRACT FROM AUTHOR]

Periostin, also termed osteoblast-specific factor 2, is a matricellular protein with known functions in osteology, tissue repair, oncology, cardiovascular and respiratory systems, and in various inflammatory settings. However, most of the research to date has been conducted in divergent and circumscribed areas meaning that the overall understanding of this intriguing molecule remains fragmented. Here, we integrate the available evidence on periostin expression, its normal role in development, and whether it plays a similar function during pathologic repair, regeneration, and disease in order to bring together the different research fields in which periostin investigations are ongoing. In spite of the seemingly disparate roles of periostin in health and disease, tissue remodeling as a response to insult/injury is emerging as a common functional denominator of this matricellular molecule. Periostin is transiently upregulated during cell fate changes, either physiologic or pathologic. Combining observations from various conditions, a common pattern of events can be suggested, including periostin localization during development, insult and injury, epithelial-mesenchymal transition, extracellular matrix restructuring, and remodeling. We propose mesenchymal remodeling as an overarching role for the matricellular protein periostin, across physiology and disease. Periostin may be seen as an important structural mediator, balancing appropriate versus inappropriate tissue adaption in response to insult/injury. [ABSTRACT FROM AUTHOR]

Bronchial asthma is a complicated and diverse disorder affected by genetic and environmental factors. It is widely accepted that it is a Th2-type inflammation originating in lung and caused by inhalation of ubiquitous allergens. The complicated and diverse pathogenesis of this disease yet to be clarified. Functional genomics is the analysis of whole gene expression profiling under given condition, and microarray technology is now the most powerful tool for functional genomics. Several attempts to clarify the pathogenesis of bronchial asthma have been carried out using microarray technology, providing us some novel biomarkers for diagnosis, therapeutic targets or understanding pathogenic mechanisms of bronchial asthma. In this article, we review the outcomes of these analyses by the microarray approach as applied to this disease by focusing on the identification of novel biomarkers. [ABSTRACT FROM AUTHOR]

Bronchial asthma is a complex disease characterized by airway inflammation involving a Th2-cytokine, interleukin (IL)-13. A substantial body of evidence has accumulated pointing to the pivotal role of IL-13 in the pathogenesis of bronchial asthma. The evidence is categorized as (i) analyses of mouse models, (ii) expression of these cytokines in the bronchial lesions, and (iii) genetic association of the signaling molecules of these cytokines. In addition, the molecular mechanism of the signal transduction of IL-13 has also been well characterized. We have applied microarray analyses to human bronchial epithelial cultures to search for genes regulated by IL-13 and have identified a subset of disease-relevant genes by comparison with cDNA libraries derived from normal and asthmatic bronchial biopsies. Expression of squamous cell carcinoma antigen-1 (SCCA1) and SCCA2, the cysteine and serine protease inhibitors, respectively, was the highest in the bronchial epithelial cells stimulated by IL-4 and IL-13 and was augmented in the asthmatic cDNA library. Furthermore, serum levels of SCCA were also elevated in asthmatic patients. Taken together, it was supposed that SCCA may play some role in the pathogenesis of bronchial asthma, and measuring its serum level may be relevant for diagnosing or monitoring the status of bronchial asthma. [ABSTRACT FROM AUTHOR]

It is widely accepted that chronic inflammation initiates and promotes carcinogenesis and tumor progression in various cell types. However, this paradigm has not been comprehensively investigated in melanoma. To investigate the effects of chronic inflammation on the progression of melanoma, we established a murine inflammatory skin model and investigated the relationship between skin inflammation and melanoma progression. In a murine model, B16F10 melanoma cells in inflamed skin grew significantly more rapidly than cells in control skin. The stromal expression of periostin was upregulated in inflamed skin, and significantly more CD163+ M2 macrophages were recruited to the melanomas in inflamed skin. We then immunohistologically examined the expression of stromal periostin and the infiltration of CD163+ M2 macrophages in human acral lentiginous melanomas (n = 94) and analyzed the statistical associations with clinicopathological variables. In human melanomas, high periostin expression and a large number of infiltrated M2 macrophages were significantly correlated with poor prognosis. Furthermore, we confirmed that periostin promotes the proliferation of murine and human melanoma cells in vitro. Our findings indicate that periostin and M2 macrophages play a critical role in melanoma progression and prognosis in both humans and mice, indicating that periostin is a potential target for treating progressive melanoma. [ABSTRACT FROM AUTHOR]

Background: Pendrin and periostin are newly identified mediators of the inflammatory process. The expression of these proteins in human sinonasal tissue and their roles in allergic rhinitis and chronic rhinosinusitis remain to be elucidated. This study investigated the expression of pendrin and periostin in sinonasal tissue of patients with allergic rhinitis, chronic rhinosinusitis, and aspirin-induced asthma. Prospective control study conducted at Yamagata University, Japan. Methods: Surgical samples were investigated by means of real-time reverse transcription-polymerase chain reaction to evaluate the expression of pendrin and periostin mRNA. The presence and location of pendrin and periostin were determined by immunohistochemistry and Western blotting. Results: Pendrin and periostin production was significantly higher in patients with nasal disorders than in controls. Further significant increases in periostin expression were noted in patients with chronic rhinosinusitis with nasal polyps and in those with aspirin-induced asthma. Immunohistochemistry revealed positive staining for pendrin in epithelial cells and submucosal glands and for periostin in the basement membrane in all three disorders, and additionally for periostin in nasal polyp tissue in chronic rhinosinusitis and aspirin-induced asthma. Conclusions: Production of pendrin and periostin is upregulated in allergic rhinitis, chronic rhinosinusitis with nasal polyps, and aspirin-induced asthma. These findings suggest that pendrin can induce mucus production and that periostin can induce tissue fibrosis and remodeling in the nasal mucosa. Therefore, these mediators may be therapeutic target candidates for allergic rhinitis, chronic rhinosinusitis with nasal polyps, and aspirin-induced asthma. [ABSTRACT FROM AUTHOR]

Bronchial asthma is a complex disease characterized by airway inflammation involving Th2 cytokines. Among Th2 cytokines, the significance of IL-13 in the pathogenesis of bronchial asthma has recently emerged. Particularly, the direct action of IL-13 on bronchial epithelial cells (BECs) is critical for generation of airway hyperresponsiveness. IL-13 has two binding units; the IL-13 receptor α1 chain transduces the IL-13 signal comprising a heterodimer with the IL-4R α chain, whereas the IL-13 receptor α2 chain (IL-13Rα2) is thought to act as a decoy receptor. However, it remains obscure how expression of these molecules is regulated in each cell. In this article, we analyzed the expression of these components in BECs. Either IL-4 or IL-13 induced intracellular expression of IL-13Rα2 in BECs, which was STAT6-dependent and required de novo protein synthesis. IL-13Rα2 expressed on the cell surface as a monomer inhibited the STAT6-dependent IL-13 signal. Furthermore, expression of IL-13Rα2 was induced in lung tissues of ovalbumin-induced asthma model mice. Taken together, our results suggested the possibility that IL-13Rα2 induced by its ligand is transferred to the cell surface by an unknown mechanism, and it down-regulates the IL-13 signal in BECs, which functions as a unique negative-feedback system for the cytokine signal. [Copyright &y& Elsevier]