Small molecule analogues of the immunomodulatory parasitic helminth product ES-62 have anti-allergy properties

Int J Parasitol. 2014 Aug;44(9):669-74. doi: 10.1016/j.ijpara.2014.05.001. Epub 2014 Jun 12.

Abstract

ES-62, a glycoprotein secreted by the filarial nematode Acanthocheilonema viteae, exhibits anti-inflammatory properties by virtue of covalently attached phosphorylcholine moieties. Screening of a library of ES-62 phosphorylcholine-based small molecule analogues (SMAs) revealed that two compounds, termed 11a and 12b, mirrored the helminth product both in inhibiting mast cell degranulation and cytokine responses in vitro and in preventing ovalbumin-induced Th2-associated airway inflammation and eosinophil infiltration of the lungs in mice. Furthermore, the two SMAs inhibited neutrophil infiltration of the lungs when administered therapeutically. ES-62-SMAs 11a and 12b thus represent starting points for novel drug development for allergies such as asthma.

Keywords: Asthma; ES-62; Immunomodulation; Parasitic helminth; Phosphorylcholine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acanthocheilonema / metabolism*
  • Animals
  • Anti-Allergic Agents / chemistry
  • Anti-Allergic Agents / immunology
  • Anti-Allergic Agents / metabolism*
  • Anti-Allergic Agents / pharmacology*
  • Cytokines / metabolism
  • Gene Expression Regulation
  • Helminth Proteins / chemistry
  • Helminth Proteins / immunology
  • Helminth Proteins / metabolism*
  • Helminth Proteins / pharmacology*
  • Immunologic Factors / chemistry
  • Immunologic Factors / immunology
  • Immunologic Factors / metabolism*
  • Immunologic Factors / pharmacology*
  • Mast Cells / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin / toxicity

Substances

  • Anti-Allergic Agents
  • Cytokines
  • ES-62 protein, Acanthocheilonema viteae
  • Helminth Proteins
  • Immunologic Factors
  • Ovalbumin