Heterogeneous Expression of Interleukin-18 and Its Receptor in B-Cell Lymphoproliferative Disorders Deriving from Naive, Germinal Center, and Memory B Lymphocytes

Airoldi, Irma; Raffaghello, Lizzia; Cocco, Claudia; Guglielmino, Roberta; Roncella, Silvio; Fedeli, Franco; Gambini, Claudio; Pistoia, Vito

doi:10.1158/1078-0432.ccr-1026-3

Cited by 34 publications

(32 citation statements)

References 48 publications

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“…Although the contribution of IL-1a/b and IL-18 in lung Th2 responses has been interpreted as an adjuvant effect through epithelial cells and APCs or a direct effect on CD4 + T cells, the role of these cytokines in B cells was previously unknown. However, recapitulating our results from this study and the fact that functional IL-1R and IL-18R are expressed on B cells (54)(55)(56), IL-1a/b and IL-18 also stimulate B cells to promote GC responses and IgE/IgG1 production during the airway instillation of pollen allergens. The results demonstrated in this study are not contradictive to the roles for IL-1 family cytokines on epithelia, myeloid APCs, or T cells that were described previously (37)(38)(39)(40).…”

Section: Discussionsupporting

confidence: 87%

“…Furthermore, the administration of IL-18 induced strong GC responses and the production of IgE (54). In humans, IL-18Ra is expressed on GC and memory B cells at higher levels than on naive B cells (55), suggesting involvement of IL-18 in GC Ab production. These studies demonstrate that direct stimulation of B cells by IL-18 can enhance the GC response and IgE production.…”

Section: Discussionmentioning

confidence: 98%

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B Cell–Intrinsic MyD88 Signaling Is Essential for IgE Responses in Lungs Exposed to Pollen Allergens

Matsushita

Yoshimoto

2014

The Journal of Immunology

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Allergen-specific IgE is linked to asthma pathogenesis, but the underlying mechanisms of IgE production in response to allergen exposure are poorly understood. In this article, we show that B cell–intrinsic MyD88 is essential for IgE/IgG1 production evoked by ragweed pollen instilled into lungs. MyD88-deficient mice showed defective IgE/IgG1 production and germinal center responses to lung instillation of ragweed pollen. However, MyD88 was dispensable for dendritic cell activation and Th2 cell development. B cell–specific deletion of MyD88 replicated the defective Ab production observed in MyD88-deficient mice. Although ragweed pollen contains TLR ligands, TLR2/4/9-deficient mice developed normal allergic responses to ragweed pollen. However, anti–IL-1R1 Ab-treated mice and IL-18–deficient mice showed decreased IgE/IgG1 production with normal Th2 development. Furthermore, B cell–specific MyD88-deficient mice showed reduced IgE/IgG1 production in response to lung instillation of OVA together with IL-1α, IL-1β, or IL-18. Thus, pollen instillation into lungs induces IL-1α/β and IL-18 production, which activates B cell–intrinsic MyD88 signaling to promote germinal center responses and IgE/IgG1 production.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 98%

B Cell–Intrinsic MyD88 Signaling Is Essential for IgE Responses in Lungs Exposed to Pollen Allergens

Matsushita

Yoshimoto

2014

The Journal of Immunology

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“…[21][22][23] It has been reported that IL-18 is localized in the dermis in the auricle at 24 hr after the elicitation of CHS with OXA. 34) Our result shows that IL-18 is also localized in the dermis before the elicitation of CHS (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…[17][18][19] IL-12 and IL-18 are produced by professional antigen presenting cells, 20) as well as lymphocytes. [21][22][23] The effect of E2 on these chemokines and cytokines has not yet been elucidated.…”

Section: Introductionmentioning

confidence: 99%

17.BETA.-Estradiol Enhances Interleukin-18 mRNA Expression after Sensitization of Mice with Contact Hypersensitivity

Sakazaki

Fujiyama

Ueno

et al. 2009

JOURNAL OF HEALTH SCIENCE

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To clarify the mechanism underlying the enhancing effect of 17β-estradiol (E2) on contact hypersensitivity (CHS) and the expression of interferon (IFN)-γ in mice, the mRNA expression levels of interleukin (IL)-18 were evaluated. Female BALB/c mice aged 3 weeks were ovariectomized, administered 3.2 µg of E2, and sensitized by 50 µl of 3% 4-ethoxymethylene-2-phenyl-2-oxazolin-one (OXA). Seven days later, CHS was elicited by the application of 7.5 µl of 1% OXA on the ear auricles. The auricles, cervical lymph nodes and spleens were excised, and gene expression was evaluated by reverse transcription-polymerase chain reaction. E2 enhanced the expression of IL-18 mRNA in the spleen on the following day and in the ear auricles on days 4 and 7 after sensitization with OXA. The preadministration of an antibody against IL-18 receptor suppressed the CHS and reduced IFN-γ mRNA expression in E2-administered mice. IL-18 was present in the dermis of the ear skin and absent in the epidermis. E2 also enhanced the expression of IFN-γ and IL-18 mRNAs in splenocytes cultured with lipopolysaccharide (LPS). IL-18 protein was detected by flow cytometry in CD4 + , CD8 + and NKG2 + lymphocytes among splenocytes cultured with LPS. These results suggest that E2 enhances lymphocyte activation in the sensitization phase of CHS, and that IFN-γ mRNA expression is enhanced in the elicitation phase of CHS.

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“…IL-18 and CA125 have comparable diagnostic potential. However, since IL-18 has also been observed in patients with squamous cell carcinoma, 39 myeloma, 40 endometriosis and endometrial cancer 41 and T-cell leukemia, 42 it is clear that IL-18 alone cannot be used as a specific marker of ovarian cancer. Although CA125 remains the best individual marker, the combination of CA125, IL-18 and FGF-2 is superior in specificity than using CA125 alone in ovarian cancer diagnosis.…”

Section: Discussionmentioning

confidence: 99%

From gene profiling to diagnostic markers: IL‐18 and FGF‐2 complement CA125 as serum‐based markers in epithelial ovarian cancer

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Ouellet

Madore

et al. 2005

Intl Journal of Cancer

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We used an oligonucleotide-based DNA microarray to identify potential markers in 39 primary cultures of ovarian cancer specimens compared with 11 primary cultures of normal ovarian epithelia. Differential gene expression of IL-18 and FGF-2 was validated on a subset of samples by quantitative PCR and by IHC, using an independent tissue array of 90 cores of 20 normal ovarian surface epithelia and 70 EOCs representing different grades and pathologies of ovarian disease. We further compared, by ELISA, these two markers with CA125 in sera from 25 cancer-free and 47 ovarian cancer patients. IL-18 and FGF-2 proteins were significantly elevated in tumor tissues (p<0.04) and sera (p<0.05) from patients with ovarian cancer. In combination, the three markers (IL-18, FGF-2, and CA125) showed similar sensitivity in scoring for ovarian cancer (35/45 patients) compared to that of CA125 alone (37/45) and significantly improved the specificity of detection (20/25 patients) compared to each marker individually (15/25 for CA125; 18/25 FGF-2; 16/25 for IL-18). In conclusion we show that a combination of the three serum markers (IL-18, FGF-2 and CA125) is associated with EOC, with higher specificity than CA125 alone. Prospective studies with a large cohort of susceptible ovarian cancer patients will be required to expand these findings. ' 2005 Wiley-Liss, Inc.

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Heterogeneous Expression of Interleukin-18 and Its Receptor in B-Cell Lymphoproliferative Disorders Deriving from Naive, Germinal Center, and Memory B Lymphocytes

Abstract: ABSTRACT

Cited by 34 publications

References 48 publications

B Cell–Intrinsic MyD88 Signaling Is Essential for IgE Responses in Lungs Exposed to Pollen Allergens

B Cell–Intrinsic MyD88 Signaling Is Essential for IgE Responses in Lungs Exposed to Pollen Allergens

17.BETA.-Estradiol Enhances Interleukin-18 mRNA Expression after Sensitization of Mice with Contact Hypersensitivity

From gene profiling to diagnostic markers: IL‐18 and FGF‐2 complement CA125 as serum‐based markers in epithelial ovarian cancer

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