IL-12-dependent vascular cell adhesion molecule-1 expression contributes to airway eosinophilic inflammation in a mouse model of asthma-like reaction.

Abstract

Bronchial-alveolar eosinophilic inflammation is among the characteristic pathological changes in asthma, which has been shown to be correlated with type 2 cytokine and chemokine production. Exogenous IL-12 has been found to be inhibitory for pulmonary eosinophilia in reported studies. Using a murine asthma-like model induced by OVA, we found in the present study that IL-12 gene knockout (KO) mice showed substantially reduced airway recruitment of eosinophils compared with wild-type control mice following OVA sensitization/challenge, although the levels of circulating eosinophils were comparable in these two groups of mice. Cytokine analysis showed Ag-driven Th1 (IFN-gamma) and Th2 (IL-4, IL-5, IL-10, and IL-13) cytokine production by CD4 T cells from local draining lymph nodes and spleen. Similarly, local eotaxin production was comparable in wild-type and IL-12 KO mice. In contrast, immunohistochemical analysis showed that the expression of VCAM-1 on the lung endothelium of IL-12 KO mice was dramatically less than that in wild-type mice. Furthermore, administration of rIL-12 at the stage of sensitization and challenge with OVA restored airway eosinophilia and VCAM-1 expression in IL-12 KO mice. The results suggest that endogenous IL-12 contributes to the recruitment of eosinophils into airways observed in asthma, possibly via enhancement of the expression of VCAM-1 on local vascular endothelial cells.

• Authors: S Wang, Y Fan, X Han, J Yang, L Bilenki, X Yang
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 166 Issue 4 Pg. 2741-9 (Feb 15 2001) ISSN: 0022-1767 [Print] United States
• PMID: 11160340 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Immunoglobulin G
• Recombinant Proteins
• Vascular Cell Adhesion Molecule-1
• Interleukin-12
• Immunoglobulin E
• Ovalbumin

Topics

• Administration, Intranasal
• Animals
• Asthma (genetics, immunology, metabolism, pathology)
• Bronchi (immunology, metabolism, pathology)
• Cytokines (biosynthesis)
• Disease Models, Animal
• Down-Regulation (genetics, immunology)
• Endothelium, Vascular (immunology, metabolism, pathology)
• Female
• Immunoglobulin E (biosynthesis)
• Immunoglobulin G (biosynthesis)
• Injections, Intraperitoneal
• Interleukin-12 (administration & dosage, deficiency, genetics, physiology)
• Intracellular Fluid (immunology, microbiology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mycobacterium bovis (immunology)
• Ovalbumin (administration & dosage, immunology)
• Pulmonary Eosinophilia (genetics, immunology, metabolism, pathology)
• Recombinant Proteins (administration & dosage)
• Th1 Cells (immunology, metabolism)
• Th2 Cells (immunology, metabolism)
• Tuberculosis, Pulmonary (genetics, immunology, pathology)
• Vascular Cell Adhesion Molecule-1 (biosynthesis, physiology)