IL-12-dependent vascular cell adhesion molecule-1 expression contributes to airway eosinophilic inflammation in a mouse model of asthma-like reaction.
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.
Wang
S
S
Immune Regulation of Allergy Research Group, Departments of Medical Microbiology and Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Fan
Y
Y
Han
X
X
Yang
J
J
Bilenki
L
L
Yang
X
X
D000281:Administration, Intranasal; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D001980:Bronchi / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007274:Injections, Intraperitoneal; D018664:Interleukin-12 / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007424:Intracellular Fluid / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009163:Mycobacterium bovis / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D011994:Recombinant Proteins / Q000008:administration & dosage; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000235:genetics / Q000276:immunology / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000502:physiology
D016207:Cytokines; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; D018664:Interleukin-12; D007073:Immunoglobulin E; D010047:Ovalbumin