Abstract
The impact of exposure to lead on gut cytokine gene expression and oral tolerance was analyzed. Oral tolerization with ovalbumin (OVA) increased levels of IL-10 and TGF-beta in gut tissue while IFN-gamma mRNA levels remained unchanged in both autoimmune diabetes prone NOD and normal C57BL/6 mice. This shift towards Th2/Th3 type cytokine gene expression was completely abolished by concomitant treatment with PbCl2 (6 x 0.5 mg/kg) in NOD mice while the cytokine balance in C57BL/6 mice was unaffected. Suppression of Th2/Th3 type cytokine expression was associated with a dampened oral tolerance response to OVA as determined by T cell proliferation assays. We conclude that in autoimmunity prone NOD mice environmental toxicants may disturb immune homeostasis by targeting the gut immune system.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Administration, Oral
-
Animals
-
Antigens / administration & dosage
-
Cytokines / genetics*
-
Diabetes Mellitus, Type 1 / genetics
-
Diabetes Mellitus, Type 1 / immunology
-
Female
-
Gene Expression / drug effects
-
Immune Tolerance / drug effects*
-
Intestine, Small / drug effects*
-
Intestine, Small / immunology*
-
Intestine, Small / metabolism
-
Lead / toxicity*
-
Mice
-
Mice, Inbred C57BL
-
Mice, Inbred NOD
-
Ovalbumin / administration & dosage
-
Ovalbumin / immunology
-
RNA, Messenger / genetics
-
RNA, Messenger / metabolism
-
Spleen / drug effects
-
Spleen / immunology
-
T-Lymphocyte Subsets / drug effects
-
T-Lymphocyte Subsets / immunology
-
Transforming Growth Factor beta / genetics
Substances
-
Antigens
-
Cytokines
-
RNA, Messenger
-
Transforming Growth Factor beta
-
Lead
-
Ovalbumin