Molecular events in human T cells treated with diesel exhaust particles or formaldehyde that underlie their diminished interferon-gamma and interleukin-10 production.
Int Arch Allergy Immunol
; 148(3): 239-50, 2009.
Article
en En
| MEDLINE
| ID: mdl-18849615
ABSTRACT
BACKGROUND:
A series of epidemiological and experimental studies have suggested that diesel exhaust particles (DEP) and formaldehyde (FA) may help trigger T helper type 2 (Th2)-mediated allergic responses.METHODS:
To identify the molecular events by which DEP and FA induce a Th2-skewed immune response, we stimulated T cells from healthy subjects with anti-CD3/anti-CD28 monoclonal antibodies and examined the effect of pretreatment with DEP or FA on mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-kappaB by Western blotting and colorimetric NF-kappaB assays. We also examined the mRNA expression profiles of the T cells by microarray and real-time PCR analyses.RESULTS:
FA selectively suppressed interferon (IFN)-gamma and interleukin-10 mRNA expression and protein production in stimulated T cells, as we previously reported with DEP. In the present study, we found that both DEP and FA suppressed NF-kappaB signaling and activated MAPKs. Both also significantly suppressed the mRNA expression of T-bet, Txk and c-Maf. Microarrays revealed significant augmentation of the expression of 2 FoxO3a-dependent genes, namely glucocorticoid-induced leucine zipper and growth arrest and DNA damage-inducible gene 45 alpha (Gadd45a), which are known to modulate T cell immune responses. Treatment with N-acetylcysteine reversed the augmented Gadd45a mRNA response and caused the suppressed IFN-gamma mRNA response to recover.CONCLUSIONS:
DEP and FA have similar transcriptional and nontranscriptional effects on T cell signaling that together promote a Th2-skewed immune response.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Emisiones de Vehículos
/
Linfocitos T
/
Interferón gamma
/
Interleucina-10
/
Contaminantes Atmosféricos
/
Formaldehído
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Humans
Idioma:
En
Revista:
Int Arch Allergy Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Japón