Suppressive effect of aqueous humor on lipopolysaccharide-induced dendritic cell maturation

Jpn J Ophthalmol. 2011 Sep;55(5):558-564. doi: 10.1007/s10384-011-0060-0. Epub 2011 Jul 20.

Abstract

Purpose: The aqueous humor (AH) contains numerous immunosuppressive molecules that contribute to the ocular immune privilege. Here, we mimic an inflammatory environment to analyze the inhibitory effects of the AH on lipopolysaccharide (LPS)-induced maturation of dendritic cells (DC).

Methods: Different concentrations of AH were added to dendritic cell cultures together with LPS. Dendritic cell surface markers CD80, CD86, and MHC-II were assessed by use of flow cytometry. Endocytic capability and mixed lymphocyte reaction were measured as functional maturation.

Results: AH inhibited LPS-induced DC maturation, resulting in down-regulated expression of CD80, CD86, MHC-II, enhancement of endocytic capacity, and reduced T cell activation. Neutralizing transforming growth factor beta 2 (TGF-β(2)) in AH can totally reverse the inhibitory effect. Treatment with prostaglandin E2 (PGE(2)) antagonist alone had no effect on DC maturation. However, blocking of both TGF-β(2) and PGE(2) in the AH resulted in synergistic suppression of the inhibiting effect of AH.

Conclusions: These results reveal that TGF-β(2) in the AH is of crucial importance in maintaining DC in the immature state. Further experiments will clarify the immune role of PGE(2) in AH.

MeSH terms

  • Animals
  • Antibodies, Neutralizing / pharmacology
  • Aqueous Humor / physiology*
  • B7-1 Antigen / metabolism
  • B7-2 Antigen / metabolism
  • Cells, Cultured
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Dextrans / metabolism
  • Dinoprostone / antagonists & inhibitors
  • Dinoprostone / physiology*
  • Down-Regulation
  • Endocytosis / physiology
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Fluorescein-5-isothiocyanate / analogs & derivatives
  • Fluorescein-5-isothiocyanate / metabolism
  • Histocompatibility Antigens Class II / metabolism
  • Lipopolysaccharides / toxicity*
  • Lymphocyte Activation
  • Lymphocyte Culture Test, Mixed
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Prostaglandin Antagonists / pharmacology
  • Swine
  • T-Lymphocytes / immunology
  • Transforming Growth Factor beta2 / antagonists & inhibitors
  • Transforming Growth Factor beta2 / physiology*
  • Xanthones / pharmacology

Substances

  • Antibodies, Neutralizing
  • B7-1 Antigen
  • B7-2 Antigen
  • Cd86 protein, mouse
  • Dextrans
  • Histocompatibility Antigens Class II
  • Lipopolysaccharides
  • Prostaglandin Antagonists
  • Transforming Growth Factor beta2
  • Xanthones
  • fluorescein isothiocyanate dextran
  • 6-isopropoxy-9-oxoxanthene-2-carboxylic acid
  • Fluorescein-5-isothiocyanate
  • Dinoprostone