The maturation-dependent production of interleukin-16 is impaired in monocyte-derived dendritic cells from atopic dermatitis patients but is restored by inflammatory cytokines TNF-alpha and IL-1beta.

Abstract

BACKGROUND:

Maturation of dendritic cells (DCs) influences important DC functions such as production of cytokines. Recently, DCs were identified as a source of interleukin-16 (IL-16), a chemotactic factor for DCs themselves, CD4+ T cells, and eosinophils. There is evidence that DC-derived IL-16 may contribute to the pathogenesis of atopic dermatitis (AD).

OBJECTIVE:

To investigate the production of IL-16 during differentiation of monocytes into DCs in healthy individuals and patients with AD.

METHODS:

IL-16 production was investigated by quantitative real-time RT-PCR, intracellular cytokine staining, immunoblotting, and ELISA.

RESULTS:

DCs generated from peripheral monocytes by 5-day culture in the presence of IL-4 and granulocyte/macrophage colony-stimulating factor acquired the capability to synthesize, store, and secrete IL-16. Storage and release of IL-16 was further enhanced during final DC maturation induced by additional 3-day culture with tumor necrosis factor-alpha (TNF-alpha) and monocyte-conditioned medium. Maturation, as determined by up-regulation of CD83 and CD86 surface expression, and production of IL-16, but not production of IL-10 and IL-12p40 was impaired in day 8 DCs derived from AD patients compared to those from healthy donors. Stimulation of day 8 DCs from AD patients with TNF-alpha and IL-1beta enhanced the expression of CD83 and CD86 and restored the production of IL-16.

CONCLUSIONS:

Signals involved in the activation and maturation of DCs enhance their capacity to produce IL-16. Functional abnormalities present in patients with AD at the monocyte level may account for impaired maturation and IL-16 production of monocyte-derived DCs.

• Authors: Kristian Reich, Sabine Hugo, Peter Middel, Volker Blaschke, Andrea Heine, Christine Neumann
• Journal: Experimental dermatology (Exp Dermatol) Vol. 13 Issue 12 Pg. 740-7 (Dec 2004) ISSN: 0906-6705 [Print] Denmark
• PMID: 15560757 (Publication Type: Journal Article)

Chemical References

• Antigens, CD
• B7-2 Antigen
• CD86 protein, human
• Cytokines
• DNA, Complementary
• Immunoglobulins
• Interleukin-1
• Interleukin-16
• Membrane Glycoproteins
• Tumor Necrosis Factor-alpha
• RNA
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Antigens, CD (biosynthesis)
• B7-2 Antigen
• Cell Differentiation
• Cell Membrane (metabolism)
• Cell Separation
• Chemotaxis
• Cytokines (metabolism)
• DNA, Complementary (metabolism)
• Dendritic Cells (cytology, metabolism)
• Dermatitis, Atopic (metabolism)
• Enzyme-Linked Immunosorbent Assay
• Flow Cytometry
• Granulocyte-Macrophage Colony-Stimulating Factor (metabolism)
• Humans
• Immunoglobulins (biosynthesis)
• Immunohistochemistry
• Inflammation
• Interleukin-1 (metabolism)
• Interleukin-16 (biosynthesis, metabolism)
• Membrane Glycoproteins (biosynthesis)
• Monocytes (metabolism)
• Phenotype
• Polymerase Chain Reaction
• RNA (metabolism)
• Time Factors
• Tumor Necrosis Factor-alpha (metabolism)
• Up-Regulation
• CD83 Antigen