Dexamethasone and FK506 Inhibit Expression of Distinct Subsets of Chemokines in Human Mast Cells

Kato, Atsushi; Chustz, Regina T.; Ogasawara, Takahisa; Kulka, Marianna; Saito, Hirohisa; Schleimer, Robert P.; Matsumoto, Kenji

doi:10.4049/jimmunol.0801375

Cited by 52 publications

(37 citation statements)

References 73 publications

(79 reference statements)

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“…Dermal mast cells are strong candidates, as they express TLR7 and produce cytokines upon Imi treatment (24). Recent studies have also shown that mast cells can produce CCL2 after anti-IgE stimulation (36). We observed that mast cells produced significant amounts of CCL2 after Imi treatment, therefore strengthening our hypothesis that mast cells are responsible for CCL2 production and subsequent pDC recruitment after topical Imi application.…”

Section: Discussionsupporting

confidence: 77%

Imiquimod clears tumors in mice independent of adaptive immunity by converting pDCs into tumor-killing effector cells

Drobits

Holcmann²,

Amberg³

et al. 2012

J. Clin. Invest.

260

255

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Section: Discussionsupporting

confidence: 77%

Imiquimod clears tumors in mice independent of adaptive immunity by converting pDCs into tumor-killing effector cells

Drobits

Holcmann²,

Amberg³

et al. 2012

J. Clin. Invest.

260

255

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“…Although they do not inhibit histamine release in human mast cells [107], they can reduce cytokine secretion by mast cells [108]. A recent study showed that topical corticosteroids (dexamethasone) treatment inhibited FcεRI-mediated up-regulation of chemokines, CCL2, CCL7, CXCL3, and CXCL8, in mast cells [109]. Calcineurin inhibitors, such as tacrolimus and pimecrolimus, have been approved by the FDA to treat moderate and severe AD [110].…”

Section: The Role Of Mast Cells Suggested By the Effect Of Therapeutimentioning

confidence: 97%

IgE, Mast Cells, and Eosinophils in Atopic Dermatitis

Liu

Goodarzi

Chen

2011

Clinic Rev Allerg Immunol

394

307

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Atopic dermatitis (AD) is a chronic inflammatory skin disease with specific immune and inflammatory mechanisms. Atopy is among the major features of the diagnosis criteria for AD but is not an essential feature. Thus, patients diagnosed with AD can be atopic or non-atopic. This review focuses on the role of IgE, mast cells, and eosinophils in the pathogenesis of AD. The known functions of IgE in allergic inflammation suggest that IgE and IgE-mediated mast cell and eosinophil activation contribute to AD, but direct evidence supporting this is scarce. The level of IgE (thus the degree of allergic sensitization) is associated with severity of AD and contributed by abnormality of skin barrier, a key feature of AD. The function of IgE in development of AD is supported by the beneficial effect of anti-IgE therapy in a number of clinical studies. The role of mast cells in AD is suggested by the increase in the mast cell number and mast cell activation in AD lesions and the association between mast cell activation and AD. It is further suggested by their role in mouse models of AD as well as by the effect of therapeutic agents for AD that can affect mast cells. The role of eosinophils in AD is suggested by the presence of eosinophilia in AD patients and eosinophil infiltrates in AD lesions. It is further supported by information that links AD to cytokines and chemokines associated with production, recruitment, and activation of eosinophils.

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“…15,17 We obtained tarsal giant papilla tissues from refractory AKC/VKC patients, all of whom were treated with topical dexamethasone eye drops for at least 4 weeks (Table 1), so treatment may have downregulated the CCL2 expression as reported previously. 18 Nonetheless, significantly higher CCL2 mRNA expression in samples from giant papillae than in conjunctival tissues obtained from conjunctivochalasis patients was observed by real-time PCR analysis (Fig. 5).…”

Section: Ccl2 Expression and Degranulation In Mast Cellsmentioning

confidence: 99%

Interaction Between Conjunctival Epithelial Cells and Mast Cells Induces CCL2 Expression and Piecemeal Degranulation in Mast Cells

Iwamoto

Asada

Ebihara

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Intraepithelial mast cells are observed in giant papillae tissue samples obtained from patients with atopic keratoconjunctivitis (AKC)/vernal keratoconjunctivitis (VKC). We examined the roles of interaction between the conjunctival epithelial cells and mast cells. METHODS.The interaction between human mast cells and conjunctival epithelial cells (HCjE) was investigated using a coculture model. Protein array analysis, ELISA, and real-time PCR were performed to test the interaction. Tissue samples (n ¼ 6) from giant papillae were resected for therapeutic purposes, and subjected to immunohistological analysis of CCL2 expression. Recombinant CCL2 (10 ng/mL) was reacted with the cultured human mast cells and ultrastructural analysis was performed. A ragweed (RW)-induced mouse experimental allergic conjunctivitis model was used to examine ccl2 mRNA expression and mast cell morphology.RESULTS. Protein array and real-time PCR analyses showed that CCL2 protein/mRNA expression was induced by mast cell-HCjE coculture. Upregulation of CCL2 mRNA was observed in mast cells, whereas in situ CCL2 expression was observed at the conjunctival epithelium of the giant papillae by immunohistochemistry. Ultrastructural analysis showed that recombinant CCL2 treatment induced piecemeal degranulation (PMD) in the mast cells. Ultrastructural analysis of tissues from the giant papillae showed PMD of mast cells within the conjunctival epithelial cells. The RW-induced experimental allergic conjunctivitis model showed increased ccl2 mRNA expression and PMD morphology in the conjunctivae. CONCLUSIONS. Mast cell-conjunctival epithelial cell interaction induces CCL2 expression and subsequent PMD.Keywords: allergy, conjunctivitis, mast cell, degranulation M ast cell activation and migration within and around the conjunctival epithelium is one of the histopathologic features of severe chronic allergic conjunctivitis, atopic keratoconjunctivitis (AKC), 1 and vernal keratoconjunctivitis (VKC).2 In our study, we investigated possible interactions of mast cells and conjunctival epithelial cells using in vitro coculture models, and we found that CCL2 expression in mast cells was upregulated by coculture. A previous report showed that CCL2 could induce piecemeal degranulation (PMD) in basophils.3 PMD and anaphylactic degranulation are known as two distinct types of mast cell degranulation. 4,5 Anaphylactic degranulation is a degranulation style with antecedent granuleto-granule and/or granule-to-plasma membrane fusions. On the other hand, gradual emptying of cytoplasmic secretory granules in the absence of granule-to-granule or granule-to-plasma membrane fusion events is observed in PMD. Previously, we reported that 34 of 168 mast cells observed in the giant papillae of eight eyes obtained from VKC patients showed PMD, whereas only 28 of the 168 mast cells had the morphology of anaphylactic degranulation. 6 These results suggested that not only anaphylactic degranulation, but also PMD might have some roles in the pathophysiology of AKC and VKC....

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Dexamethasone and FK506 Inhibit Expression of Distinct Subsets of Chemokines in Human Mast Cells

Cited by 52 publications

References 73 publications

Imiquimod clears tumors in mice independent of adaptive immunity by converting pDCs into tumor-killing effector cells

Imiquimod clears tumors in mice independent of adaptive immunity by converting pDCs into tumor-killing effector cells

IgE, Mast Cells, and Eosinophils in Atopic Dermatitis

Interaction Between Conjunctival Epithelial Cells and Mast Cells Induces CCL2 Expression and Piecemeal Degranulation in Mast Cells

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