Regulatory role of DC‐derived osteopontin in systemic allergen sensitization

Kurokawa, Masatsugu; Konno, Satoshi; Takahashi, A; Plunkett, Beverly; Rittling, Susan R.; Matsui, Yutaka; Kawa, Shigeyuki; Morimoto, Junko; Uede, Toshimitsu; Matsukura, Satoshi; Kokubu, Fumio; Adachi, Mitsuru; Nishimura, Masaharu; Huang, Shau Ku

doi:10.1002/eji.200838970

Cited by 16 publications

(15 citation statements)

References 42 publications

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“…Based on our finding that rOPN inhibits allergen sensitization (production of allergen-specific IgE antibody) [25], OPN itself may be a promising therapeutic target for the treatment of IgE-mediated allergic diseases. In this context, increases in OPN levels, as shown in our previous reports [20,21], may play a role in the efficacy of allergen immunotherapy.…”

Section: Therapeutic Strategies Against Allergy and Asthma Based On Omentioning

confidence: 99%

“…To elucidate the role of OPN in IgE-mediated allergic responses, we compared the ovalbumin (OVA)-induced specific IgE levels between wild-type (WT) and OPNdeficient (OPN À/À ) mice, and found that OPN À/À mice had significantly higher levels of OVA-induced IgE and systemic Th2 than WT mice [25]. In addition, treatment with recombinant OPN (rOPN) during intraperitoneal injection of OVA suppressed OVA-specific IgE production in WT and OPN À/À mice.…”

Section: Osteopontin Modulates Immunoglobulin E-mediated Allergic Resmentioning

confidence: 99%

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Role of osteopontin, a multifunctional protein, in allergy and asthma

Konno

Kurokawa

Uede

et al. 2011

Clin Experimental Allergy

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Osteopontin (OPN) is an extracellular matrix protein and immune modulator with a wide range of functions. OPN is recognized as a key cytokine in Th1 immune responses, yet its potential involvement in allergic/asthmatic responses has been investigated only recently. Current data from molecular and cellular studies and studies of OPN-deficient mice provide evidence that OPN plays multiple roles in the regulation of allergic responses, including regulation of IgE response, inflammatory cell migration, and the development of airway fibrosis and angiogenesis. These results suggest that OPN is a pleiotropic cytokine that functions both systemically and locally in tissue mucosa. Notably, OPN is able to exert its effects through different functional domains, and the secreted and intracellular forms of OPN may have distinct functions. Future research to elucidate all aspects of OPN function is needed to ultimately establish its role in the regulation of immune responses and various disease processes, including those critically involved in the development of allergies and asthma.

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Section: Therapeutic Strategies Against Allergy and Asthma Based On Omentioning

confidence: 99%

Section: Osteopontin Modulates Immunoglobulin E-mediated Allergic Resmentioning

confidence: 99%

Role of osteopontin, a multifunctional protein, in allergy and asthma

Konno

Kurokawa

Uede

et al. 2011

Clin Experimental Allergy

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“…Such sOPN-dependent suppression of DC migration may be mediated by, at least in part, downregulation of CCR7 in the DCs [54, 55], which enhances migration of mature DCs into regional LNs. Another study demonstrated that sOPN plays a regulatory role in systemic allergen sensitization by inducing IL-12 expression by DCs [56]. In contrast to OPN’s function in acute phase of AHR [53, 56], OPN appears to play a role as an inducer of AHR and lung remodeling in chronic phase by multiple allergen challenges [57].…”

Section: Opn and Immune-related Diseasesmentioning

confidence: 99%

Intracellular osteopontin (iOPN) and immunity

2010

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Osteopontin (OPN) is a protein, involved in various pathophysiological events. OPN has been studied as a secreted protein, but recent reports showed that OPN can be found in the cytoplasm and the nucleus. Therefore, some OPN molecules are not secreted and stay in cells. Such intracellular OPN (iOPN) has biological functions distinct from secreted OPN (sOPN). iOPN is involved in cytoskeletal rearrangement and in signal transduction pathways downstream of innate immune receptors, such as Toll-like receptors (TLRs), as an adaptor or scaffolding protein. Although sOPN and iOPN are generated from the same Opn mRNA species, biological outcomes mediated by two isoforms can be different. It would be necessary to delineate which isoform of OPN is responsible for pathophysiological events.

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“…DCs were generated from mouse bone marrow (BM) using an established protocol [18,19]. Briefly, mouse BM was obtained from the femurs and tibiae.…”

Section: Methodsmentioning

confidence: 99%

Interleukin-33-Activated Dendritic Cells Induce the Production of Thymus and Activation-Regulated Chemokine and Macrophage-Derived Chemokine

Kurokawa

Matsukura²,

Kawaguchi

et al. 2013

Int Arch Allergy Immunol

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Background: Interleukin (IL)-33, a new member of the IL-1 cytokine family, is involved in T helper (Th)2-type responses in a wide range of diseases and is mediated by expression of the ST2 receptor in many immune cells. As the effects of IL-33 on dendritic cells (DCs) remain controversial, we investigated the ability of IL-33 to modulate the functions of these cells. Methods: DCs were derived from mouse bone marrow, and the expression of the IL-33 receptor ST2 was examined by fluorescence-activated cell sorting and RT-PCR. The responses of the DCs to IL-33 were examined by RT-PCR and ELISA, and activation of mitogen-activated protein kinases (MAPKs) was determined by Western blotting. Results: ST2 ligand mRNA and protein were detectable in DCs. IL-33 induced the production of thymus and activation-regulated chemokine/CCL17 and macrophage-derived chemokine/CCL22 and the activation of extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase and p38 MAPK. Conclusions: DCs respond directly to IL-33 through ST2. The interaction between IL-33 and DCs may represent a new pathway to initiate Th2-type immune responses. IL-33 and ST2 may play important roles in allergic inflammation.

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Regulatory role of DC‐derived osteopontin in systemic allergen sensitization

Cited by 16 publications

References 42 publications

Role of osteopontin, a multifunctional protein, in allergy and asthma

Role of osteopontin, a multifunctional protein, in allergy and asthma

Intracellular osteopontin (iOPN) and immunity

Interleukin-33-Activated Dendritic Cells Induce the Production of Thymus and Activation-Regulated Chemokine and Macrophage-Derived Chemokine

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