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

Michelle S Harkins, Pope L Moseley, Gary K Iwamoto

Department of Internal Medicine, University of New Mexico Health Sciences Center, Pulmonary, Allergy & Critical Care Division, Albuquerque Veterans Affairs Medical Center, Albuquerque, New Mexico 87131, USA. mharkins@salud.unm.edu

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 2003 Dec

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Monocytic cells and alveolar macrophages (AMs) are activated in patients with asthma, producing inflammatory cytokines. This occurs despite a TH2 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-alphaffinity IgE receptor CD23. To determine the effect of the TH2 environment with interferon-gamma (IFN-gamma) and heat shock protein 70 (HSP 70) on CD23 receptor expression and tumor necrosis factor alpha (TNF-alpha) production. We examined the effect of IL-4 and IL-13 in culture with IFN-gamma 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-alpha production after cross-linking CD23 with immune complexes. Asthmatic AMs stimulated with anti-IgE exhibited a 5.7- +/- 1.9-fold increase in TNF-alpha 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-gamma 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-gamma, 2.03- +/- 0.34-fold; IL-4/IFN-gamma, 9.14- to 4.02-fold; IL-13/IFN-gamma, 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-alpha production by THP-1 cells stimulated with IFN-gamma, IL-4, IL-13, or a combination of these. Both IFN-gamma and HSP 70, in the TH2 environment, up-regulate CD23 expression and thus may play an important role in maintaining the chronic inflammatory state in asthma.

Citation

Michelle S Harkins, Pope L Moseley, Gary K Iwamoto. Regulation of CD23 in the chronic inflammatory response in asthma: a role for interferon-gamma and heat shock protein 70 in the TH2 environment. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2003 Dec;91(6):567-74