IngentaConnect Regulation of CD23 in the chronic inflammatory response in asthma...

Abstract:

Background: Monocytic cells and alveolar macrophages (AMs) are activated in patients with asthma, producing inflammatory cytokines. This occurs despite a T_H2 environment that consists of the cytokines interleukin (IL) 4, IL-10, and IL-13. The mechanism by which this occurs may involve cross-linking of the low-affinity IgE receptor CD23.

Objective: To determine the effect of the T_H2 environment with interferon- ggr

(IFN-

) and heat shock protein 70 (HSP 70) on CD23 receptor expression and tumor necrosis factor agr

(TNF-

) production.

Methods: We examined the effect of IL-4 and IL-13 in culture with IFN- ggr

and HSP 70 on CD23 expression in both THP-1 cells and AMs from healthy controls via flow cytometry. AMs from mild asthmatic patients and THP-1 cells were evaluated for TNF- agr

production after cross-linking CD23 with immune complexes.

Results: Asthmatic AMs stimulated with anti-IgE exhibited a 5.7- ± 1.9-fold increase in TNF- agr

protein. AMs from healthy controls increased the geometric mean ± SD of CD23 2.00- ± 0.50-fold in IL-4 and 2.14- ± 0.50-fold in IL-13. THP-1 cells cultured with IL-4 and IL-13 then stimulated with IFN- ggr

or HSP 70 increased CD23 expression above baseline as follows: IL-4, 2.16- ± 0.31-fold; IL-13, 2.66- ± 0.43-fold; IFN- ggr

, 2.03- ± 0.34-fold; IL-4/IFN- ggr

, 9.14- to 4.02-fold; IL-13/IFN- ggr

, 11.51- ± 5.51-fold; IL-4/HSP, 5.20- ± 0.61-fold; and IL-13/HSP, 5.60- ± 0.79-fold. Stimulating the CD23 receptor with immune complexes significantly increased TNF- agr

production by THP-1 cells stimulated with IFN- ggr

, IL-4, IL-13, or a combination of these.

Conclusions: Both IFN- ggr

and HSP 70, in the T_H2 environment, up-regulate CD23 expression and thus may play an important role in maintaining the chronic inflammatory state in asthma.

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Regulation of CD23 in the chronic inflammatory response in asthma: a role for interferon- and heat shock protein 70 in the TH2 environment

Regulation of CD23 in the chronic inflammatory response in asthma: a role for interferon- and heat shock protein 70 in the T_H2 environment