Osteopontin is involved in migration of eosinophils in asthma

Takahashi, Akiko; Kurokawa, Masatsugu; Konno, Satoshi; Ito, Koyu; Kawa, Shigeyuki; Ashino, Shigeru; Nishimura, Takashi; Uede, Toshimitsu; Hizawa, Nobuyuki; Huang, Shau Ku; Nishimura, Masaharu

doi:10.1111/j.1365-2222.2009.03249.x

Cited by 39 publications

(65 citation statements)

References 34 publications

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“…At present, the role of OPN seems to be complex, because contradictory reports have been published regarding the contribution of OPN in several inflammatory conditions [8,14,15] and dual roles of this molecule in a single disease have also been reported [16,17,34,35]. Xanthou et al recently showed that after Ag sensitization and pulmonary challenge, the levels of Ag-specific IgE were higher in OPN À/À mice when compared with OPN 1/1 mice, while administration of anti-OPN Ab during Ag sensitization suppressed Ag-specific IgE production [16].…”

Section: Discussionmentioning

confidence: 99%

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Regulatory role of DC‐derived osteopontin in systemic allergen sensitization

et al. 2009

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Osteopontin (OPN) is a secreted phosphoglycoprotein with a wide range of functions, and is involved in various pathophysiological conditions. However, the role of OPN in IgE and Th2-associated allergic responses remains incompletely defined. The aim of this study was to elucidate the role of OPN in systemic allergen sensitization in mice. When compared with OPN 1/1 mice, significantly increased levels of OVA-induced IgE were found in OPN À/À mice.OPN À/À DC demonstrated an increased capacity to enhance Th2 cytokine production in CD4 1 T cells from sensitized OPN 1/1 mice. Furthermore, significantly reduced levels of IL-12p70 expression were seen in LPS-stimulated OPN À/À DC as compared with the WT DC, and the reduction was reversible by the addition of recombinant OPN (rOPN). rOPN was able to suppress OVA-induced IL-13 production in the cultures of CD4 and OPN À/À DC, but this inhibitory activity was neutralized by the addition of anti-IL-12 Ab. In addition, administration of rOPN in vivo suppressed OVA-specific IgE production; however, this suppressive effect was abrogated in IL-12-deficient mice. These results indicate that DC-derived OPN plays a regulatory role in the development of systemic allergen sensitization, which is mediated, at least in part, through the production of endogenous IL-12.

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Section: Discussionmentioning

confidence: 99%

“…OPN's potential involvement in Th2-associated allergic responses has been investigated recently, particularly in eosinophilic airway inflammation [16,17] and in mast cell degranulation [18]. However, its role in systemic allergen sensitization via the production of allergen-specific IgE is still unclear.…”

Section: Introductionmentioning

confidence: 99%

Regulatory role of DC‐derived osteopontin in systemic allergen sensitization

et al. 2009

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“…[16][17][18] Further, several human studies have suggested that osteopontin level is increased in airway of asthmatic subjects and is associated with various asthma phenotypes. 15,[20][21][22] Additionally, the chromosomal region of 4q24 where SPP1 gene is located (4q21-q25) has been reported to be associated with atopy and with atopic disease in asthmatic subjects. 28,29 Together, these studies suggest that the osteopontin gene, SPP1, is a reasonable candidate gene for asthma susceptibility.…”

Section: Discussionmentioning

confidence: 99%

“…15 In addition, several recent studies have reported an increased level of osteopontin in bronchoalveolar lavage fluid and induced sputum in asthmatic subjects. [20][21][22] A recent genetic association study in a Japanese population has reported an association between genetic variant in the osteopontin gene, SPP1, and total serum immunoglobulin E (IgE) levels in nonasthmatic subjects, thus suggesting that osteopontin may participate in the regulation of basal IgE production. 23 Based on these observations, we hypothesized that putative functional polymorphisms in SPP1 is a risk factor for asthma and asthma phenotypes.…”

Section: Introductionmentioning

confidence: 99%

Polymorphism in Osteopontin Gene (SPP1) Is Associated with Asthma and Related Phenotypes in a Puerto Rican Population

Arjomandi

Galanter

Choudhry

et al. 2011

Pediatric Allergy, Immunology, and Pulmonology

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Recent studies have shown that osteopontin, a cytokine with suggested immunoregulatory functions, may contribute to pathogenesis of asthma. To determine whether single-nucleotide polymorphisms (SNPs) in SPP1, the gene encoding osteopontin, are associated with risk of asthma, we genotyped 6 known SNPs in SPP1 in the well-characterized Genetics of Asthma in Latino Americans population of 294 Mexican and 365 Puerto Rican parent-child asthma trios. The associations between SNPs and asthma or asthma-related phenotypes were examined by transmission disequilibrium tests as implemented in the family-based association test program. Three polymorphisms, 1 in exon 7 (rs1126616C) and 2 in the 3¢-untranslated region (rs1126772A and rs9138A) of SPP1, were associated with diagnosis of asthma, severity of asthma, asthma in subjects with elevated immunoglobulin E (IgE) (IgE > 100 IU/mL), and postbronchodilator FEV 1 in Puerto Ricans (P values = 0.00007-0.04). The CC genotype of rs1126616 conferred an odds ratio of 1.7 (95% CI = [1.3, 2.3], P value adjusted for multiple comparisons = 0.001) for asthma compared with the CT and TT genotypes. Furthermore, haplotype analysis identified rs1126616C-rs1126772A-rs9138A to be associated with an increased risk for asthma, severity of asthma, and asthma in subjects with elevated IgE (P = 0.03). There was no association between the SPP1 SNPs and asthma outcomes in Mexicans. Our findings suggest that the SPP1 gene is a risk factor for asthma and asthma-related phenotypes in Puerto Ricans, and are consistent with previous animal and human studies on the role of osteopontin in pathogenesis of asthma.

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“…In the literature, there are reports suggesting that this protein participates in the pathogenesis of asthma. Several studies have demonstrated that OPN level is increased in asthmatic patients and is associated with disease phenotypes [113][114][115][116]. In addition, the chromosomal region of 4q24 (where OPN gene is mapped) has been associated with atopy in asthmatic patients [117].…”

Section: Asthmamentioning

confidence: 99%

Osteopontin (OPN) Gene Polymorphisms and Autoimmune Diseases

Kaleta¹

2017

Genetic Polymorphisms

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Osteopontin (OPN) is a pleiotropic protein, important in bone remodeling and immune system signaling. OPN is synthesized in a variety of cells and tissues. It can be found not only in bone cells but also in immune cells (B and T lymphocytes, natural killer (NK) cells, natural killer T (NKT) cells, macrophages, neutrophils, and dendritic cells). OPN regulates T-helper 1/T-helper 2 (Th1/Th2) balance, stimulates B cells to antibodies production, regulates macrophages and neutrophils function, and activates dendritic cells. A number of factors, including hormones, cytokines, and polymorphisms of promoter region of OPN gene, regulate protein expression. OPN and variants of the OPN gene have been associated with the pathogenesis of multiple disorders, including systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, systemic sclerosis, inlammatory bowel diseases, asthma, type 1 diabetes, and many other. However, some studies gave diferent or inconclusive results. Thus, the role of OPN polymorphic variants in autoimmune diseases needs to be beter deined and explored as a diagnostic and therapeutic target to monitor and treat immune-mediated conditions.

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Osteopontin is involved in migration of eosinophils in asthma

Abstract: These results indicate that OPN plays a role in the migration of eosinophils into the airways and may be involved in the pathogenesis of asthma.

Cited by 39 publications

References 34 publications

Regulatory role of DC‐derived osteopontin in systemic allergen sensitization

Regulatory role of DC‐derived osteopontin in systemic allergen sensitization

Polymorphism in Osteopontin Gene (SPP1) Is Associated with Asthma and Related Phenotypes in a Puerto Rican Population

Osteopontin (OPN) Gene Polymorphisms and Autoimmune Diseases

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